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. To study their role in ARDS, we used a murine model of lipopolysaccharide (LPS)-induced resolving ARDS. We confirmed the development of ARDS after LPS instillation, which was resolved 14 days after onset. Using immunofluorescence and flow cytometry, we observed 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, 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.

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 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.

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.

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.

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.

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.

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.

Clinical utility of TSH receptor antibody levels in Graves' orbitopathy: a comparison of two TSH receptor antibody immunoassays.

INTRODUCTION: Thyroid stimulating hormone (TSH) receptor antibodies (TRAB) play a role in the development of Graves' orbitopathy (GO), and measurements of the TRAB level may be helpful in monitoring GO treatment. AIM OF THE STUDY: To assess the correlation of TRAB levels measured with two different assays: third-generation TRAB assay (TRAB Cobas) and novel Immulite assay (TRAB Immulite), in patients with moderate-to-severe GO treated with intravenous glucocorticoid pulse therapy (ivGCs). MATERIAL AND METHODS: Forty patients with active, moderate-to-severe GO underwent clinical and laboratory evaluation before, in the middle, and after ivGCs therapy. The correlation of TRAB levels with GO signs was evaluated. Laboratory and clinical findings were compared according to the response to ivGCs. TRAB concentration was measured with Immulite TSI assay and with Elecsys IMA. RESULTS: All patients were TRAB positive in both assays at the beginning of the treatment. The decrease of both TRAB Immulite and Cobas levels in serum during ivGCs was statistically significant. We observed strong correlation between both TRAB levels before and after ivGCs. There was no statistically significant difference in antibody levels between patients with good response and no response to the treatment. We did not find any correlation between antibody levels and GO features before the therapy, but measurements during ivGCs showed comparable correlation of both TRAB levels with GO activity. CONCLUSIONS: We found similarity between Immulite assay and third-generation TRAB assay in the assessment of patients with GO treated with ivGCs. Both TRAB levels showed comparable correlation with GO activity during ivGCs therapy.

Total testosterone to dihydrotestosterone ratio assessed by LC-MS/MS predicts a worse metabolic profile not only in PCOS patients.

OBJECTIVES: Total testosterone/dihydrotestosterone ratio (TT/DHT) was found to determine metabolic risk in polycystic ovary syndrome (PCOS). The aim of this study was to analyze whether (TT/DHT) may be helpful in predicting metabolic risk not only in PCOS patients but also in healthy women. MATERIAL AND METHODS: Total testosterone (TT), dihydrotestosterone (DHT), androstendione and dehydroepiandrosterone sulphate (DHEA-S) were measured by LC-MS/MS in 36 women with PCOS and in 29 age-matched controls without clinical hyperandrogenism. In all participants, anthropometric data, lipids, adipose tissue percent (%fat), HOMA-IR were also assessed. RESULTS: The studied groups were not different in terms of age, BMI, waist circumference, %fat and HOMA-IR. In the patients group, mean TT and androstendione levels were significantly higher as compared to controls (1.4 nmol/L vs. 1.0 nmol/L, P < 0.001) and (6.6 nmol/L vs. 4.9 nmol/L, P < 0.01), respectively. In the patients group, mean TT/DHT ratio was significantly higher compared to controls (3.6 vs. 2.7, P < 0.01) and correlated with BMI (r = 0.37, P < 0.05), waist circumference (r = 0.44, P < 0.01), %fat (r = 0.30, P < 0.05), as well as with insulin levels (r = 0.38, P < 0.05) and HOMA-IR (r = 0.44, P < 0.05). The association between TT/DHT ratio and unfavorable metabolic parameters was also seen in controls. CONCLUSION: Total testosterone/dihydrotestosterone ratio assessed by LC-MS/MS correlates with a worse metabolic profile not only in PCOS patients, but also in healthy women.

[The influence of hypothyroidism on the conversion and binding of thyroid hormones in patients with end-stage renal disease]. / Wplyw niedoczynnosci tarczycy u chorych ze schylkowa niewydolnoscia nerek na wspólczynniki konwersji i wiazania hormonów tarczycy.

Hypothyroidism in patients with renal failure (RF) causes many metabolic and clinical problems, and both these diseases can mutually exacerbate their disturbances. AIM: The aim of this study was to evaluate the effect of hypothyroidism, and end-stage renal disease (ESRD) on conversion of thyroid hormones (TH) in patients with ESRD treated with chronic hemodialysis (HD). MATERIALS AND METHODS: The study was performed in 74 patients, including 41 women (K) and 33 men (M) aged 28-83 y.o. in 4 groups: G1 - 12 people with ESRD treated with HD and with newly diagnosed hypothyroidism without substitution (6 K and M 6) aged 66,83±12,90 y.o., G2 - 26 patients with ESRD treated with HD without hypothyroidism (10 F, 16 M) aged 58,85±15,52 y.o., G3 - 11 hypothyroid patients without RF (9 K, 2 M) aged 54,73±21,26 y.o., G4 - 25-persons from control group of healthy subjects (16 M, 9 M) aged 51,24±12,58 y.o. In all subjects the concentration of TSH and TH (T4, T3, fT4, TSH, FT3, rT3) were measured and values of conversion factors (T3/T4, FT3/ fT4, rT3/fT4 and rT3/fT3) and binding TH to protein factors (fT4/T4 and fT3/T3) were calculated. RESULTS: Lower concentration of T3 (p=0.012), fT3 (p<0.001) i fT4 (p=0.014) was found in patients without hypothyroidism than in healthy subjects. Renal failure with concomitant hypothyroidism intensify the disturbances of T4 to T3 conversion (p=0.034) and hypothyroidism with concomitant renal failure disrupts binding of T3 to proteins (p=0.001). FT3 to fT4 ratio in renal failure with concomitant hypothyroidism group was significantly lower than in each other group. rT3 concentrations were the highest in healthy subjects. CONCLUSIONS: Concomitance of hypothyroidism and end-stage renal disease reduces the conversion of thyroxine to triiodothyronine, but does not increase the production of rT3. Hypothyroidism significantly increases the disorders of thyroid hormones in end-stage renal disease. There is decreased tendency to bind of thyroid hormone to protein in hypothyroidism in patients with end-stage renal disease.

The Associations Between Body Cell Mass and Nutritional and Inflammatory Markers in Patients With Chronic Kidney Disease and in Subjects Without Kidney Disease.

OBJECTIVES: Body cell mass (BCM), a component of lean tissue mass (LTM), is a metabolically active part of the body. Lean tissue loss is one of the diagnostic criteria of protein energy wasting. In patients with chronic kidney disease (CKD), a decrease of lean tissue, including BCM, may be replaced by an increase of extracellular water. Bioimpedance spectroscopy (BIS) enables the assessment of the amount of BCM, LTM, and fluid overload. The aim of our study was to assess the relationship between BCM measured by BIS and anthropometric measurements, biochemical markers of nutrition and also inflammatory markers. METHODS: Forty-eight patients treated with hemodialysis (HD; 32 males and 16 females) with a mean age 59.8 ± 15.5 (HD group), 61 patients with CKD Stage 4 to 5 (35 males and 26 females) with a mean age of 60.1 ± 17.7 (predialysis group) and 33 individuals with normal renal function (18 males and 15 women) with a mean age 58.7 ± 17.0 (control group) were included. Body mass index, handgrip strength (HGS), body composition measured by BIS, and biochemical analyses were performed on all of them. RESULTS: Positive correlations were observed between BCM and LTM, HGS, serum creatinine and insulin-like growth factor 1 concentrations in all groups. Serum prealbumin concentration correlated positively with BCM only in the predialysis group (r = 0.406; P = .001). The amount of lymphocytes also correlated passively with BCM in predialysis group (r = 0.314; P = .024). Negative correlations were noted between BCM and fat mass in all groups and between BCM and interleukin 6 concentrations only in the HD group. In this study, BCM neither correlated with body mass index and serum albumin nor with C-reactive protein. CONCLUSIONS: BCM is strongly associated with biochemical determinants of muscle mass (serum creatinine, insulin-like growth factor 1) and muscle function (HGS) in patients treated with HD, with CKD Stage 4 to 5 and in individuals without kidney disease. Its significance requires further investigation.

The morning and late-night salivary cortisol ranges for healthy women may be used in pregnancy.

OBJECTIVES: The diagnosis of adrenal dysfunction in pregnancy and in women taking oral contraceptives remains a diagnostic challenge. Salivary cortisol seems to be a useful tool for the diagnosis of Cushing's syndrome and adrenal insufficiency. However, the changes in salivary cortisol concentration in healthy pregnancy are not clearly defined. DESIGN: The aim of our study was to compare diurnal changes in salivary cortisol in healthy pregnant women, healthy controls and women on oral contraceptives. PATIENTS: The study groups consisted of (i) 41 healthy pregnant women, (ii) 42 healthy women and (iii) 12 healthy women on oral contraceptives. MEASUREMENTS: Serum and salivary cortisol in the morning and salivary late-night cortisol were measured with Roche ECLIA cortisol test (Elecsys 2010) in each trimester and postpartum. RESULTS: Despite the elevation of morning serum cortisol in the second and third trimesters of pregnancy, the morning salivary values as well as late-night salivary cortisol throughout all trimesters were not significantly different from control values (P > 0·5). In the postpartum period, the morning and late-night salivary cortisol values were significantly lower than in late pregnancy. The morning and late-night salivary cortisol values in women on contraceptives were also not different from those in the healthy women group. CONCLUSION: The results of our study suggest that reference values for salivary cortisol established for a healthy adult population can be used for pregnant women and women on oral contraceptives in the initial diagnostic testing for Cushing's syndrome and adrenal insufficiency.

HLA DQ2 HAPLOTYPE, EARLY ONSET OF GRAVES DISEASE, AND POSITIVE FAMILY HISTORY OF AUTOIMMUNE DISORDERS ARE RISK FACTORS FOR DEVELOPING CELIAC DISEASE IN PATIENTS WITH GRAVES DISEASE.

OBJECTIVE: The diagnosis of celiac disease (CD) in patients with different autoimmune diseases including Graves disease (GD) remains a challenge. The aims of our study were to: (1) assess the prevalence of CD in Polish patients with GD and (2) evaluate the prevalence of CD in the subgroups of patients with GD divided on the basis of clinical and human leukocyte antigen (HLA) typing criteria. METHODS: The prospective study was conducted at an academic referral center. The study groups consisted of consecutive, euthyroid patients with GD (n = 232) and healthy volunteers without autoimmune thyroid diseases (n = 122). The diagnosis of CD was based on elevated immunoglobulin A autoantibodies to the enzyme tissue transglutaminase (IgA-TTG) and small intestine biopsy findings. RESULTS: CD was diagnosed in 8 patients with GD (3.4%) and 1 healthy volunteer (0.8%). The development of CD in patients with GD was strongly associated with HLA-DQ2 haplotype (as predicted from linkage disequilibria, 14.6% vs. 1.5%, P = .009; odds ratio [OR] = 11.3; 95% confidence interval [CI] 1.3-252.7): 6 patients with CD carried HLA-DRB1(*)03, 1 carried an HLA-DRB1(*)04 allele, and 1 had an HLA-DRB1(*)07/(*)11 genotype. Multivariate analysis showed independent associations between CD and early GD onset (P = .014, OR = 9.6), autoimmunity in family (P = .029, OR = 6.3) and gastroenterologic symptoms (P = .031, OR = 8.1). CONCLUSIONS: The results of our study suggest that serologic screening for CD may be considered in GD patients (1) with the HLA alleles typical for CD, (2) with an early onset of GD, or (3) a family history of autoimmunity. Moreover, the diagnosis of CD should be explored in euthyroid GD patients with nonspecific gastrointestinal symptoms.

Is Free Testosterone Concentration a Prognostic Factor of Survival in Chronic Renal Failure (CRF)?

BACKGROUND: Lowered testosterone level in CRF patients is associated with elevated risk of death due to cardiovascular reasons, and is influenced by many factors, including acid-base balance disorders. AIMS: evaluation of testoste-rone concentration (TT) and free testosterone concentration (fT) in pre-dialysis and dialysis patients; assessment of TT and fT relationships with biochemical parameters; evaluation of prognostic importance of TT and fT in predicting patient survival. MATERIAL AND METHODS: 4 groups of men: 14 - on hemodialysis (HD), 13 - on peritoneal dialysis (PD), 9 - with chronic renal failure (CRF) and 8 - healthy (CG), aged 56±17, 53±15, 68±12, 43±10 years, respectively. TT and biochemical para-meters were measured; fT was calculated. RESULTS: The lowest TT and fT were observed in HD and CRF, the highest - in CG (p=0.035 for TT; p=0.007 for fT). fT in CRF and CG were different (p=0.031). TT and age was associated in HD (p=0.026). Age and fT was strongly associated in PD (p<0.001). After adjustment for age, TT was negatively associated with BMI (p=0.013) and fT was positively associated with HCO3 level (p=0.007). fT was lower in those who died during 5 years of observation than in survivors (p=0.009). We have found that, opposite to TT, fT appeared to be a better predictor of 5-year survival than age. After combining pH and HCO3 levels into a single variable - no acidosis, acidosis with HCO3 normal serum level, acidosis with low concentrations of HCO3 and adjustment for age and the study group - a trend toward the lowest values of free testosterone in decompensated acidosis was observed (ptrend=0.027). Such a trend was not seen for testosterone concentrations (ptrend=0.107). CONCLUSIONS: Total and free testosterone levels were lower in HD and pre-dialysis than in healthy patients. Free testost-erone level may predict long-term survival better than age. Total and free testosterone levels are lower in metabolic acidosis and total and free testosterone levels were positively associated with HCO3 level.

Visceral adipose tissue is associated with insulin resistance in hemodialyzed patients.

BACKGROUND: It has not been definitively established which factors affect insulin resistance (IR) and whether dialysis decreases IR. The aim of this study was to investigate factors that may have an influence on homeostasis model assessment (HOMA-IR) in hemodialyzed patients (HDpts) and to compare IR between HDpts and healthy subjects. MATERIAL AND METHODS: We examined 33 HDpts and paired 33 subjects of the control group, matched for sex, age, and BMI. We analyzed concentrations of insulin, glucose, leptin, resistin, and total and high-molecular-weight adiponectin (HMWad) in serum. Using computed tomography in HDpts, we evaluated visceral adipose tissue (VAT), concentrations of visfatin, CRP, and IL-6. RESULTS: HOMA-IR (median, 1.3 vs. 1.4, P=0.19), insulin (median 6.8 vs. 6.0 µIU/mL, P=0.7), glucose (79 mg/dL vs. 93 mg/dL, P=0.001). IR in HDpts is dependent on VAT (r=0.36, P=0.04) and this relationship is stronger than the relationship of BMI and IR (r=0.3, P=0.1). In HDpts we found higher concentrations of leptin (P=0.001) and resistin (P<0.001), with no relation to IR. HMWad and its percentage in relation to total adiponectin are higher in HDpts (P=0.03 and P<0.001, respectively). CONCLUSIONS: HOMA-IR in HDpts does not differ from the control group. In HDpts it depends on the quantity of VAT and this relationship is stronger than with BMI. In HDpts leptin and resistin do not influence IR. HMWad and its percentage in total adiponectin are significantly higher in HDpts.

LC-MS/MS improves screening towards 21-hydroxylase deficiency.

Basal serum 17OHP measurement remains the first screening step for nonclassic congenital adrenal hyperplasia (NCCAH) and the accuracy of the test is of high value. The aim of this study was to compare the accuracy of immunoassays to LC-MS/MS in the assessment of serum 17OHP and androgens concentration in women with hyperandrogenism and controls. 17OHP, total testosterone, androstendione and DHEA-S were measured in 39 women with clinically and/or biochemically evident hyperandrogenism and in 29 age-matched controls without clinical hyperandrogenism. 17OHP and androgens were measured by immunoassays and by LC-MS/MS. In patients group median 17OHP level measured by immunoassays was significantly higher compared to LC-MS/MS (5.49 nmol/l-ELISA NovaTec® and 3.57 nmol/l-ELISA DRG® versus 1.56 nmol/l-LC-MS/MS p < 0.0001) as well as in the control group (2.58 nmol/l-ELISA DRG® versus 1.14 nmol/l-LC-MS/MS p < 0.0001). Additional, unnecessary diagnostic procedures explaining elevated 17OHP level were undertaken in 85% of patients when NovaTec® test was used, in 50% when ELISA DRG® and in none when LC-MS/MS method was applied. Total testosterone, androstendione and DHEA-S concentrations in the patients and the controls assessed by the immunoassays were also significantly higher compared to LC-MS/MS. LC-MS/MS is more reliable diagnostic tool in the measurement of serum 17OHP and androgens concentrations compared to immunoassays in women with hyperandrogenism.

Interleukins 6 and 15 Levels Are Higher in Subcutaneous Adipose Tissue, but Obesity Is Associated with Their Increased Content in Visceral Fat Depots.

Excess adiposity is associated with chronic inflammation, which takes part in the development of obesity-related complications. The aim of this study was to establish whether subcutaneous (SAT) or visceral (VAT) adipose tissue plays a major role in synthesis of pro-inflammatory cytokines. Concentrations of interleukins (IL): 1ß, 6, 8 and 15 were measured at the protein level by an ELISA-based method and on the mRNA level by real-time PCR in VAT and SAT samples obtained from 49 obese (BMI > 40 kg/m²) and 16 normal-weight (BMI 20-24.9 kg/m²) controls. IL-6 and IL-15 protein concentrations were higher in SAT than in VAT for both obese (p = 0.003 and p < 0.0001, respectively) and control individuals (p = 0.004 and p = 0.001, respectively), while for IL-1ß this was observed only in obese subjects (p = 0.047). What characterized obese individuals was the higher expression of IL-6 and IL-15 at the protein level in VAT compared to normal-weight controls (p = 0.047 and p = 0.016, respectively). Additionally, obese individuals with metabolic syndrome had higher IL-1ß levels in VAT than did obese individuals without this syndrome (p = 0.003). In conclusion, concentrations of some pro-inflammatory cytokines were higher in SAT than in VAT, but it was the increased pro-inflammatory activity of VAT that was associated with obesity and metabolic syndrome.

Long-term cholecalciferol administration in hemodialysis patients: a single-center randomized pilot study.

BACKGROUND: Data on the potent pleiotropic extraskeletal effects of vitamin D have renewed interest in its use in selected populations, including patients with chronic kidney disease, but the available data are still insufficient to make recommendations. This study assessed the long-term effect of small cholecalciferol doses on serum vitamin D, parathormone (PTH), and bone mineral density (BMD) in hemodialysis patients. MATERIAL/METHODS: Nineteen patients with serum 25(OH)D <20 ng/mL were randomized into cholecalciferol (2000 IU 3×/week) and no-treatment groups, then observed for 1 year. Patients with hypercalcemia, hyperphosphatemia, and receiving vitamin D/calcimimetics were excluded. Serum 25(OH)D, 1,25(OH)2D, PTH, and alkaline phosphatase activity were examined every 2 months and BMD was measured before and after the study. RESULTS: We observed normalization of serum 25(OH)D with an increase in medians from 11.3 to 44.9 ng/mL (P=0.02) in the cholecalciferol group and no change in the controls (P<0.001). Simultaneously, median serum 1,25(OH)2D increased from 18.2 to 43.1 pmol/L (P=0.02) in the cholecalciferol group and from 10.6 to 21.2 pmol/L (P=0.02) in controls (P=0.013). The treatment was associated with a small increase in serum calcium, but serum phosphate, PTH, alkaline phosphatase, and BMD remained unchanged in both groups. CONCLUSIONS: Oral cholecalciferol at a dose of 2000 IU/3×/week is an effective and safe way to treat vitamin D deficiency in hemodialysis patients, leading to a significant increase in serum 1,25(OH)2D. However, it was insufficient to suppress the activity of parathyroid glands or to significantly change BMD.