Małgorzata Wrzosek

Vitamin D and the central nervous system.

Vitamin D is formed in human epithelial cells via photochemical synthesis and is also acquired from dietary sources. The so-called classical effect of this vitamin involves the regulation of calcium homeostasis and bone metabolism. Apart from this, non-classical effects of vitamin D have recently gained renewed attention. One important yet little known of the numerous functions of vitamin D is the regulation of nervous system development and function. The neuroprotective effect of vitamin D is associated with its influence on neurotrophin production and release, neuromediator synthesis, intracellular calcium homeostasis, and prevention of oxidative damage to nervous tissue. Clinical studies suggest that vitamin D deficiency may lead to an increased risk of disease of the central nervous system (CNS), particularly schizophrenia and multiple sclerosis. Adequate intake of vitamin D during pregnancy and the neonatal period seems to be crucial in terms of prevention of these diseases.

The CC genotype in HTR2A T102C polymorphism is associated with behavioral impulsivity in alcohol-dependent patients

High levels of impulsivity can increase the vulnerability for development of alcohol dependence. Moreover, impulsivity is considered to be a predictor of poor treatment outcomes. Few studies, however, have directly examined the genetics of impulsivity in alcohol-dependent patients. We analyzed the relationships between a well-recognized genetic marker of serotonin activity and levels of impulsivity as measured by both the Barratt Impulsiveness Scale (BIS-11) and the stop-signal task among 304 alcohol-dependent patients. The stop-signal task was used as an independent, objective method of estimating the level of behavioral impulsivity, and the BIS-11 as a self-report measure of global impulsivity. Blood was collected and analyzed for the T102C (rs6313) polymorphism in the serotonin type 2A receptor gene (HTR2A). Our results indicate a significant association between high levels of behavioral impulsivity and the C/C genotype of rs6313 in alcohol-dependent patients. The CC genotype has been previously found to be associated with a reduction in 5HT2A receptors in the central nervous system. These results support the hypothesis that genetic factors are important determinants of behavioral impulsivity in alcohol-dependent patients, and that the serotonin system plays an important role in establishing its level.

Association of polymorphisms in HTR2A, HTR1A and TPH2 genes with suicide attempts in alcohol dependence: A preliminary report

We investigated a relationship between selected polymorphisms: rs6313 in HTR2A, rs6295 in HTR1A and rs1386494 in TPH2, and suicidal behaviour in 150 alcohol-dependent patients. There was a significant association between more frequent C102C genotype in HTR2A and suicide attempts in alcoholic females. No differences in genotype distribution in HTR1A and TPH2 SNPs were found between patients with and without suicide attempts.

Vitamin D Receptor Gene BsmI Polymorphism in Polish Patients with Systemic Lupus Erythematosus

The hormonally active form of vitamin D3, 1,25(OH)2D3 (calcitriol), exerts actions through VDR receptor, which acts as a transcriptional factor. Calcitriol is an immunomodulator that affects various immune cells, and several studies link it to many autoimmune diseases. BsmI polymorphism affects the level of VDR gene transcription, transcript stability, and posttranscriptional modifications. It seems to be related to the systemic lupus erythematosus (SLE). Our study examined the characteristics of VDR gene BsmI polymorphism in Polish SLE patients and their relationship with clinical manifestations of the disease. We genotyped 62 patients with SLE and 100 healthy controls using the real-time PCR. There were no differences observed in the frequency of BsmI genotypes in SLE patients and in the control group. There was no significant correlation between BsmI genotypes and clinical symptoms of SLE, but the AA genotype correlates with higher levels of antinuclear antibodies (ANA) in this group (r = 0.438; P = 0.002). A larger study examining BsmI and other VDR gene polymorphisms is needed. It may allow explaining differences in the clinical picture of the disease and choosing a personalized therapy.

Serum cortisol concentration in patients with major depression after treatment with clomipramine.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and elevated cortisol (CORT) levels are characteristics of the pathophysiology of major depressive disorder. The aim of this study was to determine whether increased plasma CORT levels appear in patients with major depression and if effective antidepressant treatment by clomipramine (CLO) leads to regulation of CORT level. Plasma CORT levels were measured using high performance liquid chromatography (HPLC) methods in patients with major depression at time zero (before therapy) and after 3 h, 24 h, 4, 6 and 8 weeks of CLO administration. The study included 17 patients (12 women, 5 men; mean age 54.5 years, SD =12.3) and 21 healthy comparison subjects. The patients had a mean score on the 21-item Hamilton Depression Rating Scale (HDRS) of 26.8 (range 22-35). Eight of the patients with major depression recruited for the study showed a 46% increase in CORT concentration compared to the established standard. In 13 patients treated with CLO, serum CLO levels reached a therapeutic range. In recovered depressed patients, antidepressant treatment significantly reduced HDRS scores from the 6th week of treatment. A drop in plasma CORT levels in recovered depressed subjects occurred 0 to 6 weeks after CLO treatment (n = 5, p < 0.046). However, neither subject group exhibited any definitive markers of CORT secretion. In the population studied, patients had distinct profiles of HPA axis dysregulation. Finding a linear correlation between lower CORT secretion and therapeutic plasma CLO levels is the first aim of monitored therapy and may be important for understanding the pathophysiology of major depressive disorder.

New indexes of body fat distribution, visceral adiposity index, body adiposity index, waist-to-height ratio, and metabolic disturbances in the obese

BACKGROUND AND AIM The aim of this study was to examine the relationship between new obesity-related indexes, anthropometric and biochemical parameters, and body composition in individuals with obesity. METHODS The study group consisted of 72 women and 34 men, aged 39.0 ± 5.9 years, with a mean body mass index (BMI) of 32.6 ± 2.4 kg/m², admitted for body weight reduction. In all participants body weight (BW), height, waist circumference (WC), hip circumference (HC), BMI, waist-to-hip-ratio (WHR), visceral adiposity index (VAI), body adiposity index (BAI), and waist-to-height ratio (WHtR) were assessed. Using bioelectrical impedance (BIA, TANITA MC 180M) the following parameters were obtained: the level of visceral adipose tissue (VAT) and body fat percentage (FM%). Serum concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglycerides (TG), glucose, insulin, and insulin resistance (HOMA-IR) were determined. RESULTS It was observed that almost all the studied indicators: WC, WHtR, BAI, VAI, and BMI, positively correlated with VAT estimated by bioimpedance, but only VAI, WC, and WHtR were strongly associated with glucose and lipid disturbances in the obese. BAI and BMI correlated with total FM%, while WC, WHtR, and VAI correlated with total body weight. CONCLUSIONS The results indicate that VAI, WC, and WHtR can be useful in the assessment of increased VAT accumulation associated with disturbances in glucose and lipid metabolism. BAI should be calculated separately for each sex, then it could be also useful for the prediction of disturbances in glucose metabolism. However, further studies are needed to recognise cut-off values for BAI, as a marker of body fatness, associated with adverse health effects.

Oleacein enhances anti-inflammatory activity of human macrophages by increasing CD163 receptor expression.

BACKGROUND Oleacein (dialdehydic form of decarboxymethyl elenolic acid linked to hydroxytyrosol; 3,4-DHPEA-EDA) have been proven to possess antioxidant and anti-inflammatory activity. PURPOSE In this study, we examined whether oleacein could increase CD163 and IL-10 receptor expression as well as HO-1 intracellular secretion in human macrophages. METHODS Effect of oleacein (10 and 20 μmol/l) or oleacein together with complexes of haemoglobin (Hb) and haptoglobin 1-1 (Hp11) or haptoglobin 2-2 (Hp22) on expression of IL-10 and CD163 receptor was determined by Flow Cytometry. Expression of CD163mRNA was measured by real-time quantitative RT-PCR. Heme oxygenase 1 (HO-1) intracellular secretion in macrophages was investigated by enzyme-linked immunosorbent assay (ELISA). RESULTS Oleacein (OC) together with complexes HbHp11 or HbHp22 stimulated the expression of CD163 (30-100-fold), IL-10 (170-300-fold) and HO-1 secretion (60-130-fold) after 5 days of coincubation. The 2-fold (24 h), 4-fold (48 h) increase of CD163 mRNA level and its final (72 h) decrease was also observed. CONCLUSION Our results suggested that oleacein enhances anti-inflammatory activity of complexes haemoglobin with haptoglobin 1-1 and 2-2 and could play a potential role in the prevention of inflammatory disease related to atherosclerosis.

Role of Transforming Growth Factor β in Uterine Fibroid Biology

Uterine fibroids (UFs) are benign tumors of the female genital tract made of the smooth muscle of the uterus. UF growth depends mostly on the influence of the steroid hormones and selected growth factors. Transforming growth factor β (TGF-βs) is a polypeptide that consists of three isoforms: TGF-β1, TGF-β2, and TGF-β3. At present, TGF-β is considered to be one of the key factors in the pathophysiology of UFs. It plays a major role in cellular migration within the tumor, stimulates tumor growth, and enhances tumor metabolism. As a consequence of various dependencies, the synthesis and release of TGF-β in a UF tumor is increased, which results in excessive extracellular matrix production and storage. High concentrations or overexpression of TGF-β mediators may be responsible for clinically symptomatic UFs. The aim of this review was to check the available evidence for the influence of the TGF-β family on UF biology. We conducted their search in PubMed of the National Library of Medicine with the use of the following selected keywords: “uterine fibroid”, “leiomyoma”, and “transforming growth factor β”. After reviewing the titles and abstracts, more than 115 full articles were evaluated. We focused on the TGF-β-related molecular aspects and their influence on the most common symptoms that are associated with UFs. Also, we described how the available data might implicate the current medical management of UFs.

Association between rs9930506 polymorphism of the fat mass & obesity-associated (FTO) gene & onset of obesity in Polish adults

Background & objectives: The fat mass and obesity-associated (FTO) gene is known to be associated with obesity. However, no data are available on the relation between FTO rs9930506 polymorphism and obesity in Polish population. The aim of this study was to evaluate an association between rs9930506 variants of the FTO gene and obesity in Polish adults. Methods: The study group consisted of 442 adults, aged 33.9 ±12.7 yr, with mean BMI 27.2 ± 5.4 kg/m2. The following variables were determined for each subject: fasting blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides. Real-time PCR was used to detect the A/G alleles of the rs9939506 polymorphism in the FTO gene. An association between the rs9930506 polymorphism and obesity was determined using codominant, dominant, and recessive models. The odds ratio (OR) was calculated to determine the risk of obesity associated with this polymorphism. Results: It was observed that the presence of FTO rs9939506 G allele was associated with increased risk for obesity and this association was found significant in both recessive (OR = 1.72, P = 0.014) and co-dominant (OR = 1.36, P = 0.031) models of inheritance. The FTO rs9939506 GG homozygotes had a significantly higher BMI than those with other genotypes. Interpretation & conclusions: This study shows that FTO rs9939506 GG genotype is related to higher BMI and is associated with obesity in Polish adults.

Age at onset of obesity, transcription factor 7-like 2 (TCF7L2) rs7903146 polymorphism, adiponectin levels and the risk of type 2 diabetes in obese patients

Introduction Interaction between obesity and genetic factors involved in the regulatory pathways of glucose homeostasis may play a significant role in diabetes development in the obese. The aim of this study was to investigate the associations between the TCF7L2 rs7903146 polymorphism, adiponectin levels, age at onset of obesity and the occurrence of type 2 diabetes (T2D) in a sample of obese Polish adults. Material and methods A total of 474 unrelated obese subjects were included in this study. Real-time PCR was used to detect the TCF7L2 rs7903146 polymorphism. Serum level of adiponectin was determined by the ELISA method. Standard assays were used to measure total cholesterol, HDL cholesterol, triglycerides, glucose and HbA1c concentrations. We used multiple logistic regression to identify factors associated with type 2 diabetes. Results We found that the T allele of rs7903146 was significantly associated with T2D risk (odds ratio of 1.59 for T allele, p = 0.005). This association persisted after adjusting for confounders in the recessive model (odds ratio of 3.54 for TT genotype, p = 0.011). Serum adiponectin levels were significantly lower in diabetic subjects than in nondiabetic individuals (3.6 vs. 5.6 µg/ml, p < 0.001). Participants who were obese at age ≥ 20 years had significantly higher odds of having T2D (OR = 4.94) than those with the onset of obesity before 20 years (p < 0.001). Conclusions Our study highlights the significance of the relationship between the TCF7L2 polymorphism, a person’s age at onset of obesity and the prevalence of T2D, and confirms lower adiponectin levels in obese diabetics in comparison to obese nondiabetics.