Comparative analysis of post-mortem drug concentrations in cerebrospinal fluid and blood.

This study aimed to compare the concentration of various xenobiotics in both cerebrospinal fluid (CSF) and blood. We examined 175 autopsy cases covering a wide range of ages, causes of death, and drug ingestion histories, with cerebrospinal fluid and blood samples available for toxicological testing. Analytes studied included opioids, benzodiazepines, antidepressants, antipsychotics, and illicit substances such as cannabinoids, stimulants and new psychoactive substances, including synthetic cathinones and synthetic cannabinoids. We found that concentrations in CSF were generally lower than in blood. A significant correlation was observed between drug concentrations in CSF and blood for many analytes (p < 0.05). However, the strength and direction of the correlation varied considerably depending on the physicochemical properties of the drugs, suggesting that a 'one size fits all' model may not be applicable. The results indicate that cerebrospinal fluid (CSF) can be used to detect a variety of xenobiotics, particularly amphetamines, synthetic cathinones and synthetic cannabinoids, in cases where conventional biological materials are not available. Additionally, using the results obtained in the future can lead to a better understanding of pharmacokinetic processes and the effect of post-mortem redistribution. Further research is needed to refine our understanding of these relationships.

A regional comparison of children's blood cadmium, lead, and mercury in rural, urban and industrial areas of six European countries, and China, Ecuador, and Morocco.

OBJECTIVES: The authors aimed to evaluate whether blood cadmium (B-Cd), lead (B-Pb) and mercury (B-Hg) in children differ regionally in 9 countries, and to identify factors correlating with exposure. MATERIAL AND METHODS: The authors performed a cross-sectional study of children aged 7-14 years, living in 2007-2008 in urban, rural, or potentially polluted ("hot spot") areas (ca. 50 children from each area, in total 1363 children) in 6 European and 3 non-European countries. The authors analyzed Cd, Pb, and total Hg in blood and collected information on potential determinants of exposure through questionnaires. Regional differences in exposure levels were assessed within each country. RESULTS: Children living near industrial "hot-spots" had B-Cd 1.6 (95% CI: 1.4-1.9) times higher in the Czech Republic and 2.1 (95% CI:1.6-2.8) times higher in Poland, as compared to urban children in the same countries (geometric means [GM]: 0.13 µg/l and 0.15 µg/l, respectively). Correspondingly, B-Pb in the "hot spot" areas was 1.8 (95% CI: 1.6-2.1) times higher than in urban areas in Slovakia and 2.3 (95% CI: 1.9-2.7) times higher in Poland (urban GM: 19.4 µg/l and 16.3 µg/l, respectively). In China and Morocco, rural children had significantly lower B-Pb than urban ones (urban GM: 64 µg/l and 71 µg/l, respectively), suggesting urban exposure from leaded petrol, water pipes and/or coal-burning. Hg "hot spot" areas in China had B-Hg 3.1 (95% CI: 2.7-3.5) times higher, and Ecuador 1.5 (95% CI: 1.2-1.9) times higher, as compared to urban areas (urban GM: 2.45 µg/l and 3.23 µg/l, respectively). Besides industrial exposure, traffic correlated with B-Cd; male sex, environmental tobacco smoke, and offal consumption with B-Pb; and fish consumption and amalgam fillings with B-Hg. However, these correlations could only marginally explain regional differences. CONCLUSIONS: These mainly European results indicate that some children experience about doubled exposures to toxic elements just because of where they live. These exposures are unsafe, identifiable, and preventable and therefore call for preventive actions. Int J Occup Med Environ Health. 2023;36(3):349-64.

A fatal case of poisoning with a cathinone derivative: α-PiHP and its postmortem distribution in body fluids and organ tissues.

New psychoactive substances continue to appear on the drug market, and alpha-pyrrolidinoisohexanophenone (α-PiHP) is one of the most popular cathinone derivatives. In this article, we report a case of death caused by α-PiHP. Based on the toxicological results of the studied case along with autopsy, histopathological findings and crime-scene information, fatal intoxication with α-PiHP was accepted as the final cause of death. α-PiHP and its metabolite (OH-α-PiHP) were detected and quantified in all postmortem materials (blood collected from the heart, the femoral vein and the dural venous sinuses; vitreous humor; cerebrospinal fluid; cerebral cortex; brainstem; cerebellum; bile; liver; kidney; heart; pancreas; spleen; thyroid gland; lung; adipose tissue; stomach and intestine). To date, this is the first case of determination of α-PiHP and its metabolite in postmortem specimens. In our opinion, α-PiHP and its metabolite concentration database can be helpful in the interpretation of fatal cases.

The Link between Iron Turnover and Pharmacotherapy in Transplant Patients.

Iron is a transition metal that plays a crucial role in several physiological processes. It can also exhibit toxic effects on cells, due to its role in the formation of free radicals. Iron deficiency and anemia, as well as iron overload, are the result of impaired iron metabolism, in which a number of proteins, such as hepcidin, hemojuvelin and transferrin, take part. Iron deficiency is common in individuals with renal and cardiac transplants, while iron overload is more common in patients with hepatic transplantation. The current knowledge about iron metabolism in lung graft recipients and donors is limited. The problem is even more complex when we consider the fact that iron metabolism may be also driven by certain drugs used by graft recipients and donors. In this work, we overview the available literature reports on iron turnover in the human body, with particular emphasis on transplant patients, and we also attempt to assess the drugs' impact on iron metabolism, which may be useful in perioperative treatment in transplantology.

Assessing the applicability of cerebrospinal fluid collected from the spinal cord for the determination of ethyl alcohol in post-mortem toxicology.

This paper presents the results of a study on the applicability of cerebrospinal fluid (CSF) collected from the spinal canal in the post-mortem determination of ethyl alcohol. The present study reviewed data of autopsy cases (n = 45), in which ethyl alcohol was detected in CSF using gas chromatography with a flame ionization detector (HS-GC-FID), to investigate ethyl alcohol concentrations in CSF, compared with blood. As a result of statistical analysis of the obtained data, a high positive correlation was found between blood ethanol concentration and cerebrospinal fluid collected from the spinal canal ethanol concentration. The Pearson correlation coefficient was statistically highly significant (p < 0.001) (r = 0.9503). The data obtained allowed us to conclude that cerebrospinal fluid collected from the spinal canal can be collected during an autopsy as an alternative biological specimen to assess the ethanol content. Cerebrospinal fluid collected from the spinal canal can corroborate and lend credibility to the results obtained for blood and, in special cases, when blood is drawn from putrefied bodies and may even be a superior specimen to blood for assessing ethyl alcohol intoxication status.

A network meta-analysis on the comparative effect of nutraceuticals on lipid profile in adults.

It is estimated that 2.6 million deaths worldwide can be attributed to hypercholesterolemia. The main reason for non-adherence to statin therapy are the statin-associated muscle symptoms (including nocebo/drucebo effect). In this case, apart from ezetimibe, nutraceuticals are prescribed. We aimed to assess the comparative efficacy of different nutraceuticals in terms of lowering low density lipoprotein cholesterol (LDL-C) and improving lipid profile. Electronic and hand searches were performed until February 2021. The inclusion criteria were the following: (1) randomized trial with any of the reportedly LDL-C lowering nutraceutical: artichoke, berberine, bergamot, garlic, green tea extract, plant sterols/stanols, policosanols, red yeast rice (RYR), silymarin or spirulina. (2) outcome either LDL-C (primary outcome), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) or serum triglycerides (TG). Random effects network meta-analysis (NMA) was performed to rank the effect of each intervention using frequentist approach. Finally, a total of 131 trials enrolling 13,062 participants were included. All analysed nutraceuticals except for policosanols were more effective in lowering LDL-C (-1.21 [-46.8 mg/dL] to -0.17 [-6.6 mg/dL] mmol/l reduction) and TC (-1.75 [-67.7 mg/dL] to -0.18 [7 mg/dL] mmol/l reduction) than placebo/no intervention. The most effective approaches in terms of LDL-C- and TC-lowering were bergamot and RYR (-1.21 [-46.8 mg/dl] and -0.94 [-36.4 mg/dl] mmol/l) reduction respectively. In conclusion, bergamot and RYR appear to be the most effective nutraceuticals in terms of LDL-C and TC reduction. Evidence for bergamot effect was based on relatively small study group and may require further investigations. Policosanols have no effect on the lipid profile.

Association of Metabolically Healthy and Unhealthy Obesity Phenotype with Markers Related to Obesity, Diabetes among Young, Healthy Adult Men. Analysis of MAGNETIC Study.

Adipose tissue secretes many regulatory factors called adipokines. Adipokines affect the metabolism of lipids and carbohydrates. They also influence the regulation of the immune system and inflammation. The current study aimed to evaluate the association between markers related to obesity, diabesity and adipokines and metabolically healthy and unhealthy obesity in young men. The study included 98 healthy participants. We divided participants into three subgroups based on body mass index and metabolic health definition: 49 metabolically healthy normal-weight patients, 27 metabolically healthy obese patients and 22 metabolically unhealthy obese patients. The 14 metabolic markers selected were measured in serum or plasma. The analysis showed associations between markers related to obesity, diabesity and adipokines in metabolically healthy and unhealthy obese participants. The decreased level of adipsin (p < 0.05) was only associated with metabolically healthy obesity, not with metabolically unhealthy obesity. The decreased level of ghrelin (p < 0.001) and increased level of plasminogen activator inhibitor-1 (p < 0.01) were only associated with metabolically unhealthy obesity, not with metabolically healthy obesity. The decreased level of adiponectin and increased levels of leptin, c-peptide, insulin and angiopoietin-like 3 protein were associated with metabolically healthy and unhealthy obesity. In conclusion, our data show that metabolically healthy obesity was more similar to metabolically unhealthy obesity in terms of the analyzed markers related to obesity and diabesity.

Pathogenesis and Clinical Significance of In-Stent Restenosis in Patients with Diabetes.

Diabetes mellitus (DM) is a strong risk factor for the development of cardiovascular diseases such as coronary heart disease, cerebrovascular disease, and peripheral arterial disease (PAD). In the population of people living with DM, PAD is characterised by multi-level atherosclerotic lesions as well as greater involvement of the arteries below the knee. DM is also a factor that significantly increases the risk of lower limb amputation. Percutaneous balloon angioplasty with or without stent implantation is an important method of the treatment for atherosclerotic cardiovascular diseases, but restenosis is a factor limiting its long-term effectiveness. The pathogenesis of atherosclerosis in the course of DM differs slightly from that in the general population. In the population of people living with DM, more attention is drawn to such factors as inflammation, endothelial dysfunction, platelet dysfunction, blood rheological properties, hypercoagulability, and additional factors stimulating vascular smooth muscle cell proliferation. DM is a risk factor for restenosis. The purpose of this paper is to provide a review of the literature and to present the most important information on the current state of knowledge on mechanisms and the clinical significance of restenosis and in-stent restenosis in patients with DM, especially in association with the endovascular treatment of PAD. The role of such processes as inflammation, neointimal hyperplasia and neoatherosclerosis, allergy, resistance to antimitotic drugs used for coating stents and balloons, genetic factors, and technical and mechanical factors are discussed. The information on restenosis collected in this publication may be helpful in planning further research in this field, which may contribute to the formulation of more and more precise recommendations for the clinical practice.

Cerebrospinal fluid in forensic toxicology: Current status and future perspectives.

In forensic toxicology, alternative biological materials are very useful and important, e.g. in the case of lack of basic body fluids. One alternative biological material is cerebrospinal fluid (CSF). The procedures of the collection of biological material during the autopsy are performed in accordance with local, usually national recommendations, which most often require updating. It is very difficult to assess the possibility of using CSF as an alternative biological material for toxicological studies for the presence of drugs, intoxicants, including new psychoactive substances (commonly known as designer drugs), psychotropic substances, and ethyl alcohol, based on current data. Previous research suggests that CSF may be useful in toxicological studies, but these aspects need to be investigated more carefully because studies have collected CSF from different sites and often the results of different authors are not comparable. It would be necessary to prepare guidelines, e.g. the site of CSF collection that may influence the results of quantitative analysis. It would also be necessary to replicate some studies with a different collection site or a more recent analytical technique, e.g. for comparative testing of blood ethanol and cerebrospinal fluid. Cerebrospinal fluid can be a valuable information carrier in the absence of classic biological material from an autopsy. Investigating these aspects in more detail could allow the future use of this alternative material for routine toxicology analyzes in a forensic laboratory.

Oxidative Stress in Association with Metabolic Health and Obesity in Young Adults.

INTRODUCTION: Obesity is one of the most important public health problems in the world. Among obese people, there are those who, apart from excessive body weight, do not exhibit other metabolic dysfunctions, have a lower risk of developing cardiovascular diseases (CVDs), and show lower mortality. According to the theory, they are referred as metabolically healthy obese (MHO), in contrast to metabolically unhealthy obese (MUO). Metabolic disturbances occurring with obesity have been well established to be associated with oxidative stress. AIM: The purpose of this study was to analyse the association between selected anthropometric and biochemical parameters with oxidative stress in MHO, MUO, and normal weight young adults. Material and Methods. Individuals with age between 18 and 36 years with no history of chronic diseases and use of medicaments, with or without obesity, participated in the study. Complete blood counts, biochemical measurements, and parameters of oxidative stress such as total antioxidant capacity (TAC), total oxidative status (TOS), oxidative stress index (OSI), serum concentration of malondialdehyde (MDA), ceruloplasmin, thiol groups and lipid hydroperoxides (LPH), concentration of lipofuscin (LPS) in erythrocytes, and the activity of superoxide dismutase (SOD) were measured. RESULTS: 422 patients who met the inclusion criteria were enrolled in the study. Among the study participants, 208 people (49.29%) were offspring of patients with angiographically confirmed coronary artery disease. Among the participants, 16 patients have been included in the group of metabolically healthy obese (MHO) people and 61 patients in the group of metabolically unhealthy obese (MUO) people and 345 patients had normal body weight. Significant differences between metabolically unhealthy obese and normal weight patients, as well as between women and men, have been found. CONCLUSIONS: We showed significant differences in the selected parameters of oxidative stress between metabolically unhealthy obese (MUO) individuals and young volunteers with normal body weight as well as without significant medical history.

Association of Metabolically Healthy and Unhealthy Obesity Phenotypes with Oxidative Stress Parameters and Telomere Length in Healthy Young Adult Men. Analysis of the MAGNETIC Study.

Obesity is a significant factor related to metabolic disturbances that can lead to metabolic syndrome (MetS). Metabolic dysregulation causes oxidative stress, which affects telomere structure. The current study aimed to evaluate the relationships between telomere length, oxidative stress and the metabolically healthy and unhealthy phenotypes in healthy young men. Ninety-eight participants were included in the study (49 healthy slim and 49 obese patients). Study participants were divided into three subgroups according to body mass index and metabolic health. Selected oxidative stress markers were measured in serum. Relative telomere length (rTL) was measured using quantitative polymerase chain reaction. The analysis showed associations between laboratory markers, oxidative stress markers and rTL in metabolically healthy and unhealthy participants. Total oxidation status (TOS), total antioxidant capacity (TAC) and rTL were significantly connected with metabolically unhealthy obesity. TAC was associated with metabolically healthy obesity. Telomeres shorten in patients with metabolic dysregulation related to oxidative stress and obesity linked to MetS. Further studies among young metabolically healthy and unhealthy individuals are needed to determine the pathways related to metabolic disturbances that cause oxidative stress that leads to MetS.

"Obesity and Insulin Resistance" Is the Component of the Metabolic Syndrome Most Strongly Associated with Oxidative Stress.

Metabolic syndrome (MS) is not a homogeneous entity, but this term refers to the coexistence of factors that increase the risk for the development of type 2 diabetes and cardiovascular disease. There are different versions of the criteria for the diagnosis of MS, which makes the population of patients diagnosed with MS heterogeneous. Research to date shows that MS is associated with oxidative stress (OS), but it is unclear which MS component is most strongly associated with OS. The purpose of the study was to investigate the relationship between the parameters of OS and the presence of individual elements of MS in young adults, as well as to identify the components of MS by means of principal components analysis (PCA) and to investigate how the parameters of OS correlate with the presence of individual components. The study included 724 young adults with or without a family history of coronary heart disease (population of the MAGNETIC study). Blood samples were taken from the participants of the study to determine peripheral blood counts, biochemical parameters, and selected parameters of OS. In addition, blood pressure and anthropometric parameters were measured. In subjects with MS, significantly lower activity of superoxide dismutase (SOD), copper- and zinc-containing SOD (CuZnSOD), and manganese-containing SOD (MnSOD) were found, along with significantly higher total antioxidant capacity (TAC) and significantly lower concentration of thiol groups per gram of protein (PSH). We identified three components of MS by means of PCA: "Obesity and insulin resistance", "Dyslipidemia", and "Blood pressure", and showed the component "Obesity and insulin resistance" to have the strongest relationship with OS. In conclusion, we documented significant differences in some parameters of OS between young adults with and without MS. We showed that "Obesity and insulin resistance" is the most important component of MS in terms of relationship with OS.

Chronic Lower Extremity Ischemia and Its Association with the Frailty Syndrome in Patients with Diabetes.

Diabetes mellitus is an important risk factor for the development of cardiovascular diseases. Peripheral arterial disease affecting lower limb arteries is one of the clinical manifestations of atherosclerosis. The frailty syndrome (Frailty) is a problem associated with diminution of physiological reserves. The ankle-brachial index is a commonly used tool for diagnosing peripheral arterial disease (PAD). The usefulness of the ankle-brachial index (ABI) is limited in people with diabetes because of calcification of the middle layer of arteries. In this population, toe-brachial index should be measured. Frailty may be associated with worse prognosis for patients undergoing revascularization. Amputation may be an important factor leading to the development of Frailty. The risk of amputation and the prognosis after revascularization may be modified by some medications and blood glucose levels. The purpose of this paper is to review the literature about the association between PAD, especially in patients living with diabetes and Frailty.

Comparative effect of nutraceuticals on lipid profile: a protocol for systematic review and network meta-analysis.

INTRODUCTION: According to the common definition, nutraceuticals are components found in food that can act as therapeutic substances. Recently, the International Lipid Expert Panel published two position papers covering the topic of lipid-lowering nutraceuticals and their potential use as a complementary treatment in addition to statins or as an alternative treatment in statin-intolerant patients. The aim of this study was to compare the effect of different nutraceuticals on lipid profiles in a systematic review with pairwise and network meta-analyses. METHODS AND ANALYSIS: Three databases, including PubMed, Embase and the Cochrane Central Register of Controlled Trials, will be searched without time or publication language restrictions. The estimated end date for the searches will be 29 March 2020. Each stage of the review, including the study section, data extraction, and risk of bias and quality of evidence assessments, will be performed in duplicate. Randomised controlled trials meeting the following criteria will be eligible for inclusion: (1) participants aged ≥18 years, (2) intervention with a selected nutraceutical (artichoke, berberine, bergamot, soluble fibres, green tea, garlic, lupin, plant sterols and stanols, red yeast rice, soybean, spirulina or a combination of the aforementioned nutraceuticals), (3) administration of the treatment in the form of capsules, pills, powders, solutions, tablets or enriched food items, (4) comparison with another nutraceutical or placebo, (5) intervention period ≥3 weeks and (6) lipid profile (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol, triglycerides) as an outcome. Random-effect pairwise and network meta-analyses will be used to summarise the relative effect of each nutraceutical in comparison to the effect of every other nutraceutical. Subgroup analyses will be stratified by age, sex, ethnicity, sample size, length of trial follow-up, baseline cholesterol level and presence of other comorbidities. ETHICS AND DISSEMINATION: This review will summarise findings from primary studies, and therefore no ethics approval is required. The results will be presented at conferences as well as published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42019132877.

Genetic and environmental factors associated with homocysteine concentrations in a population of healthy young adults. Analysis of the MAGNETIC study.

BACKGROUND AND AIMS: Elevated homocysteine concentration is associated with a higher risk of cardiovascular disease. The aim of our study was to determine the environmental and genetic factors associated with serum homocysteine concentration in healthy young adults. Moreover, we aimed to determine the cutoff value of homocysteine concentration for predicting unfavorable MTHFR genotype and to investigate whether this association is modified by dietary patterns and serum folate status. METHODS AND RESULTS: A total of 744 healthy individuals, aged 18-35 years, were included in the study. Diet quality was assessed by establishing diet quality scores and adherence to the pro-Healthy Diet Index (pHDI) and non-Healthy Diet Index (nHDI). Genotyping was performed using the TaqMan method. Multivariate analysis showed that pHDI, creatinine, folate concentrations, and the T/T genotype of the C677T polymorphism in MTHFR, as well as the interaction between the T/T genotype of MTHFR (C677T polymorphism) and folate level, were most strongly related to homocysteine concentrations. The specificity of a homocysteine >13.1 µmol/l in predicting T/T homozygous status was 76% (area under the curve 0.68). CONCLUSION: Healthy dietary patterns, folate, and creatinine levels, as well as the C677T polymorphism, proved to be the strongest predictors of homocysteine concentrations. T/T genotype of MTHFR modifies the relationship between folate and homocysteine.

Calcium and Phosphate Levels are Among Other Factors Associated with Metabolic Syndrome in Patients with Normal Weight.

BACKGROUND AND PURPOSE: We aimed to assess the association between calcium and phosphorous and metabolic syndrome (MetS) in normal-weight individuals. PATIENTS AND METHODS: The study sample comprised 460 normal-weight (body mass index <25kg/m2) adults aged 18-35 years. The diagnosis of MetS was based on the presence of at least two of the following: 1) systolic blood pressure (SBP) ≥130 mmHg or diastolic blood pressure (DBP) ≥85 mmHg, 2) triglycerides (TG) >150 mg/dl, 3) high-density lipoprotein cholesterol (HDL-C) <1 mmol/in men and <1.2 mmol/l in women, 4) total cholesterol (TC) >5.2 mmol/l, and 5) fasting glucose (FBG) >5.55 mmol/l. RESULTS: Patients with MetS were more often male and slightly older and they had a higher body mass index (BMI) and waist circumference. By definition, patients with MetS had higher levels of BP, GLC, glycated hemoglobin A1c, TC, low-density lipoprotein cholesterol (LDL-C), TG, and apolipoprotein B but significantly lower concentrations of HDL-C and apolipoprotein A. Moreover, subjects with MetS had higher activity of the liver enzymes alanine aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase (GGTP). Higher concentrations of uric acid, creatinine and albumin (ALB) were also observed in subjects with MetS. The factors associated with MetS in the multivariate analysis were higher GGTP activity (OR per 5 unit increase - 1.23 (1.11-1.37); p<0.0001), a higher BMI (OR - 1.28 (1.1-1.52); p=0.003), a higher concentration of calcium (OR per 0.1 mmol/l increase - 1.79 (1.21-2.7); p=0.004), higher ALB levels (OR per 5 g/l increase - 1.76 (1.11-2.95), p=0.02); higher phosphorous levels (OR per 0.1 mmol/l increase - 0.82 (0.67-0.99); p=0.04), and a good household situation (odds ratio (OR) - 0.58 95% confidence interval (CI) (0.31-1.07); p=0.08). CONCLUSION: Calcium and phosphorus levels are significantly associated with MetS in normal-weight individuals.

Metabolically healthy obese and metabolic syndrome of the lean: the importance of diet quality. Analysis of MAGNETIC cohort.

BACKGROUND: Obesity is considered as an indispensable component of metabolic health assessment and metabolic syndrome diagnosis. The associations between diet quality and metabolic health in lean, young adults have not been yet established whilst data addressing this issue in overweight and obese subjects is scarce. Our analysis aimed to establish the link between diet quality (measured with data-driven dietary patterns and diet quality scores) and metabolic syndrome (MS) in young adults, regardless of their adiposity status. METHODS: A total of 797 participants aged 18-35 years old were included in the study. Participants were assigned into metabolic syndrome (MS) group if at least two abnormalities within the following parameters were present: blood pressure, triglycerides, total cholesterol, HDL cholesterol, blood glucose. Participants with one or none abnormalities were considered as metabolically healthy subjects (MH), Diet quality was assessed with two approaches: 1) a posteriori by drawing dietary patterns (DPs) with principal component analysis (PCA) and 2) a priori by establishing diet quality scores and the adherence to pro-Healthy-Diet-Index (pHDI) and non-Healthy-Diet-Index (nHDI). Logistic regression with backward selection based on Akaike information criterion was carried out, to identify factors independently associated with metabolic health. RESULTS: Within the MS group, 31% were of normal weight. Three PCA-driven DPs were identified, in total explaining 30.0% of the variance: "Western" (11.8%), "Prudent" (11.2%) and "Dairy, breakfast cereals & treats" (7.0%). In the multivariate models which included PCA-driven DPs, higher adherence to middle and upper tertiles of "Western" DP (Odds Ratios [OR] and 95% Confidence Intervals [95% CI]: 1.72, 1.07-2.79 and 1.74, 1.07-2.84, respectively), was associated with MS independently of clinical characteristics including BMI and waist-hip ratio (WHR). Similar results were obtained in the multivariate model with diet quality scores - MS was independently associated with higher scores within nHDI (2.2, 0.92-5.28). CONCLUSIONS: Individuals with MS were more likely to adhere to the western dietary pattern and have a poor diet quality in comparison to metabolically healthy peers, independently of BMI and WHR. It may imply that diet composition, as independent factor, plays a pivotal role in increasing metabolic risk. Professional dietary advice should be offered to all metabolically unhealthy patients, regardless of their body mass status.

Total antioxidant status reduction conditioned by a serum selenium concentration decrease as a mechanism of the ultrasonographically measured brachial artery dilatation impairment in patients with arterial hypertension.

The objective of the study was to determine the relationship between serum concentrations of selenium (SeS) and zinc (ZnS), total antioxidant status (TAS) and endothelial function assessed by ultrasonographic method of dilatation of the brachial artery in 141 hypertensive patients. Patients with SeS < median were characterized by a statistically significantly lower flow-mediated dilation (FMD) than patients with SeS ≥ median. Patients with TAS < median were characterized by a significantly lower FMD than patients with TAS ≥ median. Older age, higher BMI, male gender, higher blood total cholesterol, ischemic heart disease, smoking and lower SeS constitute independent predictors of inferior endothelial function, expressed in lower FMD values. Smoking is an independent predictor of lower TAS, and the use of ß-blockers and higher serum selenium levels are independent predictors of higher TAS. In summary, a decrease in TAS should be considered as a mechanism of inferior endothelial function in hypertensive patients conditioned by a decrease in SeS.

Alleviating Effect of α-Lipoic Acid and Magnesium on Cadmium-Induced Inflammatory Processes, Oxidative Stress and Bone Metabolism Disorders in Wistar Rats.

Cadmium exposure contributes to internal organ dysfunction and the development of chronic diseases. The aim of the study was to assess the alleviating effect of α-lipoic acid and/or magnesium on cadmium-induced oxidative stress and disorders in bone metabolism, kidney and liver function, and hematological and biochemical parameters changes. Male rats were exposed to cadmium (30 mg Cd/kg of feed) for three months. Some animals exposed to Cd were supplemented with magnesium (150 mg Mg/kg of feed) and/or with α-lipoic acid (100 mg/kg body weight, four times a week). Cd intake inhibited body weight gain and lowered hemoglobin concentration, whereas it increased the activities of liver enzymes, as well as the level of oxidative stress, CTX-1 (C-terminal telopeptide of type I collagen, bone resorption marker), and CRP (C-reactive protein, marker of inflammation); it decreased vitamin D3, GSH (reduced glutathione), and the serum urea nitrogen/creatinine index. Mg and/or α-lipoic acid supplementation increased the antioxidant potential, and partially normalized the studied biochemical parameters. The obtained results show that both magnesium and α-lipoic acid decrease oxidative stress and the level of inflammatory marker, as well as normalize bone metabolism and liver and kidney function. Combined intake of α-lipoic acid and magnesium results in reinforcement of the protective effect; especially, it increases antioxidant defense.

Genetically determined metabolism of nicotine and its clinical significance.

Enzymes of the cytochrome P-450 (CYP 450) which belong to the family of oxidase enzymes, are present in cells of all organisms and play a major role in the first phase of xenobiotic metabolism. There are several isoenzymes of CYP 450 that show differences in the speed of metabolism: poor-, extensive- and ultra-rapid. Nicotine undergoes biotransformation in the liver mainly by the CYP2A6 isoform of CYP 450. There are many polymorphic isoforms of CYP2A6 affecting the metabolism of nicotine. There are also several CYP2A6 activity inhibitors and inducers among commonly used drugs. The ability of CYP2A6 isozymes to activate certain procancerogenic substances present in cigarette smoke makes their polymorphism more significant. Moreover, some isoforms may have also influence on the risk of lung cancer development by affecting the enzymatic activation of tobacco-specific nitrosamines. Metabolism of nicotine, mainly through CYP2A6, has also many clinical implications, such as efficacy and safety of the nicotine replacement therapy (NRT) or occurrence of several diseases. In summary, type of the nicotine metabolism may be a potential predictor of the clinical outcomes in patients with cardiovascular disease, addicted to nicotine and in those using NRT. The purpose of this work is to summarize current knowledge on variation in genetically determined metabolism of nicotine and its clinical significance.