The Role of microRNA in the Regulation of Cortisol Metabolism in the Adipose Tissue in the Course of Obesity.

The similarity of the clinical picture of metabolic syndrome and hypercortisolemia supports the hypothesis that obesity may be associated with impaired expression of genes related to cortisol action and metabolism in adipose tissue. The expression of genes encoding the glucocorticoid receptor alpha (GR), cortisol metabolizing enzymes (HSD11B1, HSD11B2, H6PDH), and adipokines, as well as selected microRNAs, was measured by real-time PCR in adipose tissue from 75 patients with obesity, 19 patients following metabolic surgery, and 25 normal-weight subjects. Cortisol levels were analyzed by LC-MS/MS in 30 pairs of tissues. The mRNA levels of all genes studied were significantly (p < 0.05) decreased in the visceral adipose tissue (VAT) of patients with obesity and normalized by weight loss. In the subcutaneous adipose tissue (SAT), GR and HSD11B2 were affected by this phenomenon. Negative correlations were observed between the mRNA levels of the investigated genes and selected miRNAs (hsa-miR-142-3p, hsa-miR-561, and hsa-miR-579). However, the observed changes did not translate into differences in tissue cortisol concentrations, although levels of this hormone in the SAT of patients with obesity correlated negatively with mRNA levels for adiponectin. In conclusion, although the expression of genes related to cortisol action and metabolism in adipose tissue is altered in obesity and miRNAs may be involved in this process, these changes do not affect tissue cortisol concentrations.

Tissue Inhibitors of Metalloproteinase 1 (TIMP-1) and 3 (TIMP-3) as New Markers of Acute Kidney Injury After Massive Burns.

BACKGROUND Acute kidney injury (AKI) is a common and serious complication after massive burn injury. One of the postulated etiologies is destruction of the extracellular matrix of nephrons, caused by a local imbalance between matrix metalloproteinases (MMPs) and specific inhibitors. The aim of this study was to analyze the dynamics of tissue inhibitors of metalloproteinases (TIMPs) during the first 5 days after massive thermal injury and the relationship with the risk of AKI. MATERIAL AND METHODS Thirty-three adults (22 men, 11 women) with severe burns were enrolled in the study. The values of TIMPs 1 to 4 were measured in blood serum and urine using the multiplex Luminex system. The associations between TIMPs and the risk of AKI were analyzed by using the generalized linear mixed models for repeated measurements. RESULTS Significant changes in serum and urine activities of TIMPs were confirmed, especially during the first 2 days after burn injury. Almost half of patients presented renal problems during the study. Significant differences between values of TIMPs in AKI and non-AKI status were also observed. However, a significant relationship between concentration of TIMPs and risk of AKI was confirmed only for urine TIMP-1 and serum TIMP-3. CONCLUSIONS The evaluation of TIMPs in the early stage after burn injury has potential benefits. The important roles of urine TIMP-1 and serum TIMP-3, as novel markers of the risk of AKI development, were confirmed. Other parameters require further analysis.

The Role of Pericytes in Lipopolysaccharide-Induced Murine Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is a heterogeneous clinical syndrome that is most commonly triggered by infection-related inflammation. Lung pericytes can respond to infection and act as immune and proangiogenic cells; moreover, these cells can differentiate into myofibroblasts in nonresolving ARDS and contribute to the development of pulmonary fibrosis. Here, we aimed to characterize the role of lung cells, which present characteristics of pericytes, such as peri-endothelial location and expression of a panel of specific markers. A murine model of lipopolysaccharide (LPS)-induced resolving ARDS was used to study their role in ARDS. The development of ARDS was confirmed after LPS instillation, which was resolved 14 days after onset. Immunofluorescence and flow cytometry showed early expansion of neural-glial antigen 2+ ß-type platelet-derived growth factor receptor+ pericytes in murine lungs with loss of CD31+ ß-type platelet-derived growth factor receptor+ endothelial cells. These changes were accompanied by specific changes in lung structure and loss of vascular integrity. On day 14 after ARDS onset, the composition of pericytes and endothelial cells returned to baseline values. LPS-induced ARDS activated NOTCH signaling in lung pericytes, the inhibition of which during LPS stimulation reduced the expression of its downstream target genes, pericyte markers, and angiogenic factors. Together, these data indicate that lung pericytes in response to inflammatory injury activate NOTCH signaling that supports their maintenance and in turn can contribute to recovery of the microvascular endothelium.

AGER-1 Long Non-Coding RNA Levels Correlate with the Expression of the Advanced Glycosylation End-Product Receptor, a Regulator of the Inflammatory Response in Visceral Adipose Tissue of Women with Obesity and Type 2 Diabetes Mellitus.

The advanced glycosylation end-product receptor (AGER) is involved in the development of metabolic inflammation and related complications in type 2 diabetes mellitus (T2DM). Tissue expression of the AGER gene (AGER) is regulated by epigenetic mediators, including a long non-coding RNA AGER-1 (lncAGER-1). This study aimed to investigate whether human obesity and T2DM are associated with an altered expression of AGER and lncAGER-1 in adipose tissue and, if so, whether these changes affect the local inflammatory milieu. The expression of genes encoding AGER, selected adipokines, and lncAGER-1 was assessed using real-time PCR in visceral (VAT) and subcutaneous (SAT) adipose tissue. VAT and SAT samples were obtained from 62 obese (BMI > 40 kg/m2; N = 24 diabetic) and 20 normal weight (BMI = 20-24.9 kg/m2) women, while a further 15 SAT samples were obtained from patients who were 18 to 24 months post-bariatric surgery. Tissue concentrations of adipokines were measured at the protein level using an ELISA-based method. Obesity was associated with increased AGER mRNA levels in SAT compared to normal weight status (p = 0.04) and surgical weight loss led to their significant decrease compared to pre-surgery levels (p = 0.01). Stratification by diabetic status revealed that AGER mRNA levels in VAT were higher in diabetic compared to non-diabetic women (p = 0.018). Elevated AGER mRNA levels in VAT of obese diabetic patients correlated with lncAGER-1 (p = 0.04, rs = 0.487) and with interleukin 1ß (p = 0.008, rs = 0.525) and resistin (p = 0.004, rs = 0.6) mRNA concentrations. In conclusion, obesity in women is associated with increased expression of AGER in SAT, while T2DM is associated with increased AGER mRNA levels and pro-inflammatory adipokines in VAT.

Resistin Contribution to Cardiovascular Risk in Chronic Kidney Disease Male Patients.

BACKGROUND: Resistin is a molecule that belongs to the Resistin-Like Molecules family (RELMs), the group of proteins taking part in inflammatory processes. Increased resistin concentrations are observed in cardiovascular complications. Resistin contributes to the onset of atherosclerosis and intensifies the atherosclerotic processes. The aim of this study was to investigate the relationship between resistin and cardiovascular (CV) risk in men with chronic kidney disease (CKD) not treated with dialysis. MATERIALS AND METHODS: One hundred and forty-two men were included in the study: 99 men with eGFR lower than 60 mL/min/1.73 m2 and 43 men with eGFR ≥ 60 mL/min/1.73 m2. CV risk was assessed. Serum resistin, tumor necrosis factor-alpha (TNF-alpha) and plasminogen activator inhibitor-1 (PAI-1) were measured among other biochemical parameters. RESULTS: We observed that resistin concentrations were significantly higher in patients with CKD compared to individuals with eGFR ≥ 60 mL/min/1.73 m2 (p = 0.003). In CKD, after estimating the general linear model (GLM), we found that resistin is associated with CV risk (p = 0.026) and PAI-1 serum concentrations (0.012). The relationship of PAI-1 with resistin depends on the level of CV risk in CKD (p = 0.048). CONCLUSIONS: Resistin concentrations rise with the increase of CV risk in CKD patients and thus resistin may contribute to the progression of cardiovascular risk in this group of patients. The relationship between resistin and CV risk is modified by PAI-1 concentrations.

Left Ventricular Diastolic Dysfunction in Chronic Kidney Disease Patients Not Treated with Dialysis.

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is observed in the early stages of chronic kidney disease (CKD) and may lead to heart failure with preserved ejection fraction (HFpEF). The purpose of our study was to investigate the association between metabolic, nutritional and inflammatory parameters and LVDD in CKD and non-CKD patients. METHODS: Two groups of patients were recruited to the study: 93 men with CKD and eGFR lower than 60 mL/min/1.73 m2 and 40 men without kidney function decrease with eGFR ≥ 60 mL/min/1.73 m2. Transthoracic echocardiography was performed to evaluate the diastolic function of the left ventricle. Bioimpedance spectroscopy (BIS) was used to measure overhydration and lean body mass. We also measured the serum concentrations of albumin, glucose, haemoglobin A1c (HgbA1c), fibrinogen, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha) and osteoprotegerin (OPG). RESULTS: We observed that elevated serum fibrinogen and glucose concentrations were associated with LVDD independently of CKD status. Serum fibrinogen concentrations increased with the advancement of LVDD. Low albumin concentrations in CKD were related with LVDD. In the control group, lower muscle mass presented as lean tissue index (LTI) and lean tissue mass (LTM), and overhydration were associated with LVDD. In the group of patients without kidney function decrease the OPG concentrations were significantly higher in those with LVDD, and they rose with the advancement of LVDD. CONCLUSIONS: Elevated inflammatory parameters, increased serum glucose concentrations and worse nutritional status are the states that may impair the diastolic function of the left ventricle in CKD and non-CKD patients. Serum OPG levels are elevated in patients without kidney function decrease and LVDD and its concentrations rise with the advancement of LVDD.

Serum Osteoprotegerin Is an Independent Marker of Left Ventricular Hypertrophy, Systolic and Diastolic Dysfunction of the Left Ventricle and the Presence of Pericardial Fluid in Chronic Kidney Disease Patients.

BACKGROUND: Osteoprotegerin (OPG) is a molecule which belongs to the tumor necrosis factor receptor superfamily. OPG concentration is elevated in patients with left ventricle hypertrophy, heart failure and acute myocardial infarction. OPG concentrations rise in chronic kidney disease (CKD). The aim of this study was to investigate the association between OPG concentrations and cardiovascular complications, such as left ventricle hypertrophy, systolic and diastolic dysfunction of left ventricle and dysfunction of right ventricle in chronic kidney disease patients not treated with dialysis. The relation between OPG and the amount of pericardial fluid was also examined. METHODS: One hundred and one men with CKD stage 3-5 not treated with dialysis were included in the study. Overhydration, body fat mass and lean body mass were measured using bioimpedance spectroscopy (BIS). Echocardiography was performed to evaluate the amount of pericardial fluid and to measure the thickness of the interventricular septum (IVS), systolic and diastolic function of left ventricle, as well as systolic function of right ventricle. RESULTS: We observed a significant positive association between OPG and the thickness of the interventricular septum, the size of the left atrium (LA) and the presence of pericardial fluid. A negative relationship was observed between OPG and ejection fraction (EF). CONCLUSIONS: Our results suggest that OPG can be an independent marker of left ventricular hypertrophy, systolic and diastolic dysfunction of left ventricle and the presence of pericardial fluid in chronic kidney disease patients.

The Influence of Time of Day of Vaccination with BNT162b2 on the Adverse Drug Reactions and Efficacy of Humoral Response against SARS-CoV-2 in an Observational Study of Young Adults.

An increasing body of evidence from both academic and clinical studies shows that time-of-day exposure to antigens might significantly alter and modulate the development of adaptive immune responses. Considering the immense impact of the COVID-19 pandemic on global health and the diminished efficacy of vaccination in selected populations, such as older and immunocompromised patients, it is critical to search for the most optimal conditions for mounting immune responses against SARS-CoV-2. Hence, we conducted an observational study on 435 healthy young adults vaccinated with two doses of BNT162b2 (Pfizer-BioNTech) vaccine to determine whether time-of-day of vaccination influences either the magnitude of humoral response or number of adverse drug reactions (ADR) being reported. We found no significant differences between morning and afternoon vaccination in terms of both titers of anti-Spike antibodies and frequency of ADR in the studied population. In addition, our analysis of data on the occurrence of ADR in 1324 subjects demonstrated that the second administration of vaccine in those with previous SARS-CoV-2 infection was associated with lower incidence of ADR. In aggregate, vaccination against COVID-19 with two doses of BNT162b2 mRNA vaccine is presumed to generate an equally efficient anti-Spike humoral response.

Relationships between Sclerostin, Leptin and Metabolic Parameters in Non-Dialysis Chronic Kidney Disease Males.

Sclerostin is an inhibitor of the Wnt-beta-catenin pathway. The relationship between sclerostin and adipose tissue or between sclerostin and nutritional status has been the subject of research interest in the last decade. Sclerostin concentrations are elevated in patients with chronic kidney disease (CKD). Leptin is an adipocytokine which inhibits food intake by stimulating the satiety center in the hypothalamus. Leptin concentrations rise with the reduction of eGFR (glomerular filtration rate). The aim of this study was to investigate the possible association between sclerostin and leptin, between sclerostin and selected poor prognostic factors of CKD progression, and between sclerostin and nutritional parameters in non-dialysis CKD male patients. 101 men with non-dialysis CKD stage 3-5 were included in the study. Bioimpedance spectroscopy (BIS) was used to measure body composition. Blood samples were drawn to measure the serum concentrations of sclerostin, leptin, creatinine, hemoglobin (Hgb), parathormone (PTH), inflammatory markers, and markers of nutritional status. We also measured homeostatic model assessment of insulin resistance (HOMA-IR) as well as blood pressure. We observed a significant, positive relationship between sclerostin and age, leptin, and glycated hemoglobin (HgbA1c) concentrations. A significant, negative association was observed between sclerostin and eGFR. Sclerostin is associated with leptin in non-dialysis CKD male patients. Sclerostin is also related to metabolic disturbances such as hyperglycemia in this population.

Free testosterone levels and their association with body composition in women with chronic kidney disease.

Data concerning the influence of sex hormones on body composition in women with chronic kidney disease (CKD) is limited. AIM: The aim of our study was to define free testosterone levels and their association with body composition, biochemical markers of nutrition in females with CKD. MATERIALS AND METHODS: 47 women were included into the study. 13 females treated with hemodialysis formed the hemodialysis group (HD), 24 females with CKD stage IV/V (eGFR < 30 ml/min/1,73 m2) formed the predialysis group (PreD), and 10 females without kidney disease formed the control group (C). Lean tissue mass (LTM) and fat mass (Fat) were measured using bioimpedance spectroscopy. Free testosterone levels were assessed using ELISA (IBL International). Statistical analysis was performed using Statistica v 13.1. RESULTS: The median free testosterone (fT) levels were 0.7, 0.6, 0.85 pg/ml respectively for HD, PreD and C group. The median fT did not differ significantly between the groups (p=0.24). The mean LTM was 28.5 ±5.6, 27.3 ±4.9, 30.6 ±4.3 kg, mean Fat mass was 22.7 ±8.5, 31.3 ±9.8, 31.6 ±8.5 kg for the HD, PreD and C groups respectively. Positive correlations were observed between fT and LTM (r=0.306, p=0.035) in the whole study group. A negative correlation was observed between fT and age (r=-0.284) but was on the border of statistical significance (p=0.052). CONCLUSIONS: In women with advanced CKD, median testosterone levels did not differ significantly from those observed in women without kidney failure. Free testosterone levels were associated with the amount of muscle mass in the whole study population.

Serum Osteoprotegerin Is an Independent Marker of Metabolic Complications in Non-DialysisDependent Chronic Kidney Disease Patients.

BACKGROUND: Osteoprotegerin (OPG) belongs to the tumour necrosis factor superfamily and is known to accelerate endothelial dysfunction and vascular calcification. OPG concentrations are elevated in patients with chronic kidney disease. The aim of this study was to investigate the association between OPG levels and frequent complications of chronic kidney disease (CKD) such as anaemia, protein energy wasting (PEW), inflammation, overhydration, hyperglycaemia and hypertension. METHODS: One hundred non-dialysis-dependent men with CKD stage 3-5 were included in the study. Bioimpedance spectroscopy (BIS) was used to measure overhydration, fat amount and lean body mass. We also measured the serum concentrations of haemoglobin, albumin, total cholesterol, C-reactive protein (CRP), fibrinogen and glycated haemoglobin (HgbA1c), as well as blood pressure. RESULTS: We observed a significant, positive correlation between OPG and age, serum creatinine, CRP, fibrinogen, HgbA1c concentrations, systolic blood pressure and overhydration. Negative correlations were observed between OPG and glomerular filtration rate (eGFR), serum albumin concentrations and serum haemoglobin level. Logistic regression models revealed that OPG is an independent marker of metabolic complications such as anaemia, PEW, inflammation and poor renal prognosis (including overhydration, uncontrolled diabetes and hypertension) in the studied population. CONCLUSION: Our results suggest that OPG can be an independent marker of PEW, inflammation and vascular metabolic disturbances in patients with chronic kidney disease.

Maternal and neonatal serum expression of the vascular growth factors in hyperglycemia in pregnancy.

INTRODUCTION: Hyperglycemia in pregnancy (HIP) occurs in up to 8-17% of pregnancies. Unfavorable impact of the pregnancy induced hyperglycemia on both maternal and fetal tissues is associated with adverse pregnancy outcomes. Vascular growth factors, especially in the early phase of gestation, are considered as one of the most significant molecules that regulate pregnancy course and their serum expression may be altered in patients affected with HIP. MATERIAL AND METHODS: Fifty-five consecutive pregnant patients who underwent elective cesarean section were incorporated into this study. During the surgery, maternal and cord blood samples were collected. Serum expression levels of vascular growth factors: PlGF, VEGF, THBS-2 and Ang-2 were compared among non-HIP and pregnancies affected by gestational diabetes. Subsequently, laboratory results were correlated with obstetric outcomes. RESULTS: There were no statistical differences in maternal characteristics, neonatal outcomes and maternal or neonatal serum levels between study and control groups. However, our results revealed significant differences between fetal and maternal levels of VEGF (p = .028 and .0001), THBS-2 (p = .013 and .0014) and Ang-2 (p = .035 and .048) for HIP and non-HIP group, respectively. CONCLUSIONS: Similar serum expressions of vascular growth factors in and non-HIP and HIP pregnancies point that normal glycemia due to thorough prenatal surveillance may result in normal angio- and vasculogenesis associated with good pregnancy outcomes.

Adrenocorticotropin/cortisol ratio - a marker of psoriasis severity.

INTRODUCTION: The hypothalamic-pituitary-adrenal (HPA) axis plays a crucial role in systemic homeostasis and hormonal regulation of metabolic and immune functions. A similar HPA axis analog exists in the skin, where it regulates inflammation, cell proliferation and differentiation. Data regarding central HPA axis dysregulation in psoriasis are interesting but so far inconclusive. AIM: In the study we attempted to determine whether central HPA axis serum components correlate with psoriasis severity. MATERIAL AND METHODS: Forty-two patients (10 women and 32 men) hospitalized at the Department of Dermatology participated in the study. None of our patients received any systemic treatment. Venous blood samples were collected at 6.00 AM. The relationship between quantitative variables and psoriasis severity based on the Psoriasis Area and Severity Index (PASI) was assessed with proc logistic in SAS 9.4. RESULTS: The effect of adrenocorticotropin/cortisol ratio on the PASI group was OR 3.621 (95% confidence limits 1.217-10.775) for a 0.1 change in ratio (p = 0.02), meaning ACTH/cortisol ratio positively correlates with psoriasis severity. The effect of ACTH and cortisol on the PASI group was not statistically significant, with p-values of 0.30 and 0.23 respectively. Other inflammatory markers such as high-sensitivity C-reactive protein, neutrophils level, LDL, and total cholesterol did not show a significant correlation with PASI score. CONCLUSIONS: Our results support the role of HPA axis dysfunction in the complex pathogenesis of psoriasis, showing a positive correlation between morning ACTH/cortisol ratio and disease severity. ACTH/cortisol ratio can be regarded as a new biochemical marker of psoriasis severity worth further studies.

Plasma growth differentiation factor 15 levels for predicting serious adverse events and bleeding in acute pulmonary embolism: a prospective observational study.

INTRODUCTION: Growth differentiation factor 15 (GDF­15), a cytokine induced in the myocardium by pressure overload and ischemia, has a well­established prognostic role for diseases of the left ventricle. Plasma GDF­15 concentrations were shown to predict bleeding events in patients with atrial fibrillation on anticoagulation. OBJECTIVES: To investigate the prognostic value of GDF­15 in acute pulmonary embolism (PE). PATIENTS AND METHODS: This was a prospective observational study of 77 patients hospitalized for PE. The median length of hospital stay and follow-up was 9 days. Plasma GDF­15 levels were measured using an automated sandwich electrochemiluminescence immunoassay. The outcome measures were: 1) in­hospital serious adverse events (SAE; death, cardiopulmonary resuscitation, need for urgent reperfusion therapy, catecholamine administration), and 2) major bleeding or nonmajor clinically relevant bleeding. RESULTS: There were 12 SAE and 5 bleeding events. The median (interquartile range) GDF­15 concentration at admission was 2354 ng/l (1151-4750 ng/l). GDF­15 concentrations increased according to risk subgroup. Patients with serious adverse events or bleeding events had higher baseline concentrations of GDF­15 (median [interquartile range], 3460 ng/l [2 531-12 363 ng/l] vs 2034 ng/l [1121-4449 ng/l]; P = 0.01). The area under the curve for GDF­15, high­sensitivity cardiac troponin T, and N­terminal pro-brain natriuretic peptide concentrations for predicting SAE was similar, the area under the curve of GDF­15 levels for predicting bleeding was 0.783 (95% CI, 0.62-0.946; P = 0.001) and 0.71 (95% CI, 0.567-0.853; P = 0.004) for predicting any adverse event. In the multivariable analysis, GDF­15 greater than 1680 ng/l emerged as an independent predictor of adverse outcomes (odds ratio, 8.9; P = 0.047). CONCLUSIONS: Plasma GDF­15 concentrations may be a promising biomarker for predicting hemodynamic destabilization and bleeding complications in PE.

Can aminopeptidase N determined in the meconium be a candidate for biomarker of fetal intrauterine environment?

AIM: To investigate possible association of aminopeptidase N/CD13 with other parameters of possible homeostatic mechanisms in meconium for potential use in identifying intrauterine environmental stress factors during fetal and perinatal life. METHODS: Aminopeptidase N/CD13 (APN/CD13), calprotectin (CAL), myeloperoxidase (MPO), ceruloplasmin (CER), lactoferrin (LF) and interleukin-8 (IL-8) were determined using ELISA kits in 115 meconium samples collected from 30 healthy full term neonates. RESULTS: Significant correlations were established between meconium APN/CD13 [µg/g] (mean ± SD, median, range: 2.88 ± 9.90, 0.94, 0.09-91.54) and MPO (r = 0.77, p = .0000), CER (r = 0.48, p = .0000), LF (r = 0.26, p = .005), IL-8 (r = 0.44, p = .00012) but no correlation of APN/CD13 vs CAL (r = 0.15, p > .05). With increased APN/CD13 concentrations there were increases (p < .05) in concentrations of MPO, CER, LF and L-8. CONCLUSIONS: Meconium APN/CD13 demonstrates characteristic associations with other proteins involved in the regulation of metabolic processes. The panel of APN/CD13, MPO, CER and LF may be candidate biomarker for disorders developing in utero which may have impact on health in later life.

Stereotypical and Actual Associations of Breast Size with Mating-Relevant Traits.

Breast size varies substantially among women and influences perception of the woman by other people with regard to her attractiveness and other characteristics that are important in social contexts, including mating. The theory of sexual selection predicts that physical criteria of partner selection should be markers of the candidate's desirable properties, mainly biological quality. Few studies, however, have examined whether breast size really signals biological quality or its components and whether observers accurately interpret these signals. Our first study encompassed 163 young women and aimed to establish actual correlates of breast size. The aim of the second study was to determine preferences and stereotypes related to breast size: 252-265 women and men evaluated female digital figures varying in, among other characteristics, breast size. Breast size (breast circumference minus chest circumference) was negatively associated with body asymmetry and positively associated with infections of the respiratory system, but did not correlate with infections of the digestive system, openness to casual sex, and testosterone and estradiol level. Women and men perceived breasts in a similar way to each other: the bigger the breasts the higher the reproductive efficiency, lactational efficiency, sexual desire, and promiscuity attributed to the woman. Nevertheless, large breasts were not regarded more attractive than average ones, though small breasts were the least attractive. In addition, big-breasted women were perceived as less faithful and less intelligent than women with average or small breasts. We discuss our results from the perspectives of evolutionary psychology, perceptual biases, and social stereotypes.

Vitamin D Receptor Gene Expression in Adipose Tissue of Obese Individuals is Regulated by miRNA and Correlates with the Pro-Inflammatory Cytokine Level.

Background: Given the role that vitamin D (VD) plays in the regulation of the inflammatory activity of adipocytes, we aimed to assess whether obesity changes the expression of VD-related genes in adipose tissue and, if so, to investigate whether this phenomenon depends on microRNA interference and how it may influence the local inflammatory milieu. Methods: The expression of genes encoding VD 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1) and receptor (VDR), selected interleukins and microRNAs was evaluated by real-time PCR in visceral (VAT) and in subcutaneous (SAT) adipose tissues of 55 obese (BMI > 40 kg/m2) and 31 normal-weight (BMI 20-24.9 kg/m2) individuals. Results: VDR mRNA levels were higher, while CYP27B1 levels were lower in adipose tissues of obese patients than in those of normal-weight controls (VAT: P = 0.04, SAT: P < 0.0001 and VAT: P = 0.004, SAT: P = 0.016, respectively). The expression of VDR in VAT of obese subjects correlated negatively with levels of miR-125a-5p (P = 0.0006, rs = -0.525), miR-125b-5p (P = 0.001, rs = -0.495), and miR-214-3p (P = 0.009, rs = -0.379). Additionally, VDR mRNA concentrations in visceral adipose tissues of obese subjects correlated positively with mRNA levels of interleukins: 1ß, 6 and 8. Conclusions: We observed obesity-associated up-regulation of VDR and down-regulation of CYP27B mRNA levels in adipose tissue. VDR expression correlates with the expression of pro-inflammatory cytokines and may be regulated by miRNAs.

The effect of biotin interference on the results of blood hormone assays.

Approximately 70% of medical decisions are made based on results of laboratory investigations. Immunochemical methods are used most commonly in routine laboratory diagnostics of endocrine disorders. Those methods are limited by susceptibility of the immunochemical reaction to various interferences. Interference may be caused by the presence of autologous antibodies, heterophilic antibodies, or paraproteins in the blood serum, by cross-reactions with similar reagents, haemolysis, significant lipidaemia, or hyperbilirubinaemia. Some recent reports have indicated a significant effect of biotin on the reliability of laboratory investigations. Biotin is a water-soluble vitamin belonging to the B group. It is present in popular dietary supplements - alone or as a component of multi-vitamin formulas - and it is advertised as a remedy to falling out and fragility of hair and nails. Due to its low molecular weight and a strong affinity to streptavidin, biotin is used in many immunochemical tests. Due to a strong and stable bond of streptavidin and biotin, analytical methods using the streptavidin (avidin)-biotin system are characterised by superior sensitivity, and they allow determination of very low levels of the tested substance in biological material. The presence of exogenous biotin in a sample may cause interference when using tests that utilise the streptavidin (avidin)-biotin system. Interference of biotin with immunochemical tests depends on several factors: the construction of the immunochemical test, the dose used by the patient, the biotin concentration in the sample, and most of all - the time from the last dose to the collection of biological material for laboratory testing. In this paper we present some practical recommendations and a procedure to be followed in the case of suspected interference of biotin in immunochemical assays, for clinicians and laboratory diagnosticians.

Simple platelet markers: Mean platelet volume and congestive heart failure coexistent with periodontal disease. Pilot studies.

BACKGROUND: Conducted pilot study concerning mean platelet volume (MPV) parameter among patients suffering from congestive heart failure and periodontal disease. METHODS: Examination of dynamic changes of platelet and periodontal markers in group of 50 patients before and an average of 6 months subsequent to professional periodontal treatment. RESULTS: Both platelet and periodontal parameters decreased after periodontal treatment, what is more, the decrease of MPV value due to periodontal disease/mm improvement was shown to be statistically significant (p = 0.05). CONCLUSIONS: Improvement of periodontal status may influence decrease of MPV value and increase of congestive heart failure treatment efficacy and effect patient comfort. It is a new, not frequently used pattern of chronic disease treatment optimalization.

The influence of hypothyroidism and substitution treatment on thyroid hormone conversion ratios and rT3 concentration in patients with end-stage renal failure.

INTRODUCTION: The increasing number of patients with end-stage renal disease (ESRD) requires seeking new opportunities to improve their quality of life, not only because of kidney disease but also due to other disturbances, such as thyroid hormone disorders. The objective of the study was to evaluate the influence of coexisting hypothyroidism and thyroid hormone therapy in patients with ESRD on thyroid hormone conversion ratios and rT3 concentration. MATERIAL AND METHODS: The study involved 85 patients aged 26 to 87 years, with a mean age of 59.62 ± 15.45 years. Four groups of patients were examined: G1 group - 25 persons without RF and hypothyroidism, G2 - 26 patients with ESRD treated with haemodialysis (HD), G3 - 12 patients with ESRD treated with HD and newly diagnosed hypothyroidism, and G4 - 22 HD patients with hypothyroidism treated with thyroid hormones substitution. The concentrations of TSH, T4, T3, fT4, fT3, and rT3 were measured and the fT3/fT4, T3/T4, and rT3/T4 conversion ratios and rT3/T3 ratio were calculated. Concentrations of protein, hsCRP, Hg, and blood gases were also checked; the anion gap was calculated. RESULTS: Patients from group G1 through G2 to G3 were older (ptrend = 0.002), with lower Hb level (ptrend < 0.001), with lower pH (ptrend < 0.001), with increased anion gap (ptrend < 0.013) and CRP concentrations (ptrend < 0.001), and decreased total protein level (ptrend < 0.001). There were increased TSH values (ptrend < 0.001) and lower T4 (ptrend = 0.024), fT3 (ptrend < 0.001), T3 (ptrend < 0.001), and rT3 (ptrend = 0.008) levels. rT3/T3 ratio did not change, the rT3/T4 ratio tended to decrease (ptrend = 0.065) similarly to T3/T4 ratio (ptrend = 0.063), and the fT3/fT4 ratio also decreased (ptrend = 0.005). It seems that the treatment of thyroid disease in patients with renal failure, treated with haemodialysis, is not associated with change of rT3 and conversion factor levels. CONCLUSIONS: The concentration of rT3 in HD patients in relation to healthy persons tends to decrease, and hypothyroidism increases this tendency in these patients. Hormone substitution treatment does not eliminate the influence of RF on inhibition of rT3 production. In patients with ESRD, hypothyroidism additionally reduces the conversion of thyroid hormones examined by fT3/fT4 and to a lesser extent T3/T4 ratios.