Fatty acid composition of adipose tissue changes with weight loss. Palmitoleic acid as a possible marker of endogenous lipogenesis or its functions as a lipokine are under debate. Objective was to assess the predictive role of adipose triglycerides fatty acids in weight maintenance in participants of the DIOGENES dietary intervention study. After an 8-week low calorie diet (LCD) subjects with > 8 % weight loss were randomized to 5 ad libitum weight maintenance diets for 6 months: low protein (P)/low glycemic index (GI) (LP/LGI), low P/high GI (LP/HGI), high P/low GI (HP/LGI), high P/high GI (HP/HGI), and a control diet. Fatty acid composition in adipose tissue triglycerides was determined by gas chromatography in 195 subjects before the LCD (baseline), after LCD and weight maintenance. Weight change after the maintenance phase was positively correlated with baseline adipose palmitoleic (16:1n-7), myristoleic (14:1n-5) and trans-palmitoleic acid (16:1n-7t). Negative correlation was found with baseline oleic acid (18:1n-9). Lower baseline monounsaturated fatty acids (14:1n-5, 16:1n-7 and trans 16:1n-7) in adipose tissue triglycerides predict better weight maintenance. Lower oleic acid predicts lower weight decrease. These findings suggest a specific role of monounsaturated fatty acids in weight management and as weight change predictors., M. Kunešová, ... [et al.]., and Obsahuje seznam literatury
Bariatric surgery is the most effective method in the treatment of obesity and type 2 diabetes (T2DM). The aim of this study was to evaluate the effects of different types of bariatric procedures on remission of T2DM and on the fatty acid composition in subcutaneous adipose tissue. Patients included obese diabetic women who underwent bariatric surgery: biliopancreatic diversion (BPD), n=8, laparoscopic gastric banding (LAGB), n=9 or laparoscopic greater curvature plication (LGCP), n=12. Anthropometric characteristics and fatty acid composition of adipose tissue (FA AT) were analyzed before surgery, then 6 months and 2 years after surgery. FA AT was analyzed by gas chromatography. Diabetes remission was estimated. BPD was most efficient in inducing a remission of diabetes (p=0.004). Significantly higher increases in lauric (12:0), myristoleic (14:1n-5) and palmitoleic (16:1n-7) acids and delta-9 desaturase were found two years after BPD, suggesting higher lipogenesis in adipose tissue. Docosatetraenoic acid (22:4n-6) increased significantly after BPD, while docosapentaenoic acid (22:5n-3) decreased 6 months after BPD and increased after 2 years. No changes were found after LAGB and LGCP after 2 years. Bariatric surgery led to significant changes in the fatty acid composition of subcutaneous adipose tissue in severely obese diabetic women after six months and two years, and was partly influenced by the type of surgery used., M. Kunešová, B. Sedláčková, O. Bradnová, E. Tvrzická, B. Staňková, P. Šrámková, K. Dolešalová, P. Kalousková, P. Hlavatý, M. Hill, B. Bendlová, M. Fried, V. Hainer, J. Vrbíková., and Obsahuje bibliografii
A common variant of the LHb subunit has a varying prevalence in various ethnic groups. The consequences of the presence of mutated luteinizing hormone (LH) concern borderline alterations in pituitary/gonadal function that could be mediated by an altered action of variant LH on gonadal steroidogenesis. A comparison of plasma concentrations of gonadal steroid sex hormones was completed in women heterozygous for variant LH and in women with the wild type of LH in three different age ranges. The sample was a randomly selected group of 177 normal women 16 to 72 years old. Variant LH was determined by immunofluorimetric methods using two combinations of monoclonal antibodies. The ratios of LH measured by the two assays indicated whether the subject was wild type homozygote, heterozygote or homozygote for the variant LHb allele. The carriers of the variant LH allele in the group of postmenopausal women showed higher serum testosterone levels than those with the wild type LH. This is in agreement with the clinical observations made previously showing a slightly higher androgenic action in the population with variant LH. No differences were detected in serum LH, FSH, epitestosterone and sex hormone binding globulin (SHBG)., M. Hill, I.T. Huhtaniemi, R. Hampl, L. Stárka., and Obsahuje bibliografii
Multiple sclerosis (MS) is one of the most common neurological diseases. This neurodegenerative autoimmune disease manifests as inflammatory and demyelinating impairment of the central nervous system (CNS). Although some studies demonstrated associations between altered steroidogenesis and pathophysiology of MS as well as the importance of steroids in the pathophysiology of MS, the knowledge concerning the steroid metabolome in female patients is limited. Hence, 51 steroids and steroid polar conjugates were measured in the serum of 12 women with MS, untreated with steroids and 6 agecorresponding female controls with the use of gas chromatography - mass spectrometry (GC-MS). The data were processed using age adjusted ANCOVA, receiver operating characteristics (ROC) analysis and orthogonal projections to latent structures (OPLS). Our data show higher levels of circulating C21 steroids including steroid modulators of ionotropic type A γ-aminobutyric acid (GABA A) receptors and glutamate receptors. Furthermore, the levels of GABAergic androsterone and 5-androsten-3β,7α,17β-triol were also higher in the female MS patients. In conclusion, the data demonstrate higher levels of circulating C21 steroids and their polar conjugates and some bioactive C19 steroids in women with MS, which may influence neuronal activity and affect the balance between neuroprotection and excitotoxicity., R. Kanceva, L. Stárka, L. Kancheva, M. Hill, M. Veliková, E. Havrdová., and Obsahuje bibliografii
Glucocorticoid (GC) therapy is one of the methods of choices for treatment of autoimmune diseases (ADs). In addition, adrenal androgens are known as immunoprotective GC-antagonists. Adrenal steroids preferentially influence the Th1-components over the Th2 ones. We investigated steroid metabolome (using gas chromatography-mass spectrometry) in healthy controls (H), GC-untreated patients with ADs different from IgA nephropathy (U), GC-treated patients with ADs different from IgA nephropathy (T) and in patients with IgA nephropathy (IgAN), which were monitored on the beginning (N0), after one week (N1) and after one month (N2) of prednisolone therapy (60 mg of prednisolone/day/m2 of body surface). Between-group differences were assessed by one-way ANOVA, while the changes during the therapy were evaluated by repeated measures ANOVA. The ANOVA testing was followed by Duncan’s multiple comparisons. IgAN patients and patients with other ADs exhibited lack of adrenal androgens due to attenuated activity of adrenal zona reticularis (ZR). Androgen levels including their 7α-, 7β-, and 16α-hydroxy-metabolites were further restrained by GC-therapy. Based on these results and data from the literature, we addressed the question, whether a combination of GCs with Δ5-steroids or their more stable synthetic derivatives may be optimal for the treatment of antibodies-mediated ADs., I. Šterzl, M. Hill, L. Stárka, M. Velíková, R. Kančeva, J. Jemelková, L. Czerneková, P. Kosztyu, J. Zadražil, K. Matoušovic, K. Vondrák, M. Raška., and Obsahuje bibliografii
Our aim was to analyze the correlation of early postoperative cortisol levels in patients after transsphenoidal pituitary adenoma surgery compared to the standard dose ACTH test and Insulin tolerance test (ITT) several months later. We retrospectively reviewed data from 94 patients operated for pituitary adenoma in years 2009-2012. The comparison of day 7 (median) postoperative basal cortisol levels and 3.6 months (median) after pituitary adenoma surgery stimulation test - standard dose 250 μg 1-24ACTH test in 83 patients or ITT in 11 patients were performed. All 16 patients with early postoperative cortisol levels >500 nmol/l proved a sufficient response in the stimulation tests. At basal cortisol levels of 370-500 nmol/l the sufficient response was found in 96 % (27/28) of patients. In the postoperative basal cortisol levels 200-370 nmol/l we found a preserved corticotroph axis later on in 88 % (28/32) of cases. Patients with basal cortisol levels 100-200 nmol/l had a maintained corticotroph axis function in 8/11 cases - 73 %. All patients with an early postoperative basal cortisol level above 500 nmol/l proved in the stimulation tests a preserved corticotroph axis function. The interval 370-500 nmol/l showed a minimal risk of postoperative adrenal insufficiency., V. Hána Jr., J. Ježková, M. Kosák, M. Kršek, J. Marek, D. Netuka, M. Hil, V. Hána., and Obsahuje bibliografii
Steroids are important components in the pathophysiology of Alzheimer’s disease (AD). Although their role has been studied, the corresponding metabolomic data is limited. In the present study we evaluate the role of steroid sulfotransferase SULT2A1 in the pathophysiology of AD on the basis of circulating steroids (measured by GC-MS), in which the sulfation catalyzed by SULT2A1 dominates over glucuronidation (pregnenolone/sulfate, DHEA/sulfate, androstenediol/sulfate and 5α-reduced pregnane and androstane catabolites). To estimate a general trend of SUL2A1 activity in AD patients we compared the ratios of steroid conjugates to their unconjugated counterparts (C/U) in controls (11 men and 22 women) and AD patients (18 men and 16 women) for individual circulating steroids after adjustment for age and BMI using ANCOVA model including the factors AD status and gender. Decreased C/U ratio for the C19 steroids demonstrate an association between attenuated sulfation of C19 steroids in adrenal zona reticularis and the pathophysiology of AD., M. Vaňková, M. hill, M. Velíková, J. Včelák, G. Vacínová, P. Lukášová, D. Vejražková, K. Dvořáková, R. Rusina, I. Holmerová, E. Jarolímová, H. Vaňková, B. Bendlová., and Obsahuje bibliografii
Determination of response of cortisol and its metabolites to different stimuli may be important for adrenal gland disorders. To date, only one metabolite, cortisone, has been followed in stimulation tests of the adrenal gland. We aimed to describe a response of cortisol metabolites to the standard short Synacthen test (HDST), insulin tolerance test (ITT), low dose Synacthen test (LDST) and medium dose Synacthen test (MDST). Sixty healthy subjects were investigated: 30 men and 30 women. Plasma for measurements of cortisol and its metabolites was obtained before and 30th and 60th min after Synacthen and insulin administration. The cut-off 500 nmol/l of cortisol was reached after stimulation in all of tests, the maximal stimulation level was reached in 60th min in all of the tests except for LDST. The response of cortisol and its metabolites at 30th and 60th min strongly correlated in all of the tests except for LDST. Cortisol and its metabolites increased after stimulation; in contrast, cortisone and its metabolites decreased. We showed that the response of the cortisol metabolites during the Synacthen tests and ITT well correlated, and the MDST showed similar response compared to HDST. The decrease in cortisone metabolites may correspond to the regeneration of cortisol from cortisone in response to stimulation test., K. Simunkova, M. Duskova, M. Kosak, M. Krsek, V. Hana, M. Hill, H. Jandikova, H. Pospisilova, M. Sramkova, E. Bifulco, L. Starka., and Obsahuje bibliografii
Salivary cortisol reflects the free fraction of serum cortisol. Monitoring salivary cortisol may be a promising alternative method for assessing serum cortisol in some clinical situations. We aimed to compare the reliability of salivary vs. serum cortisol during ACTH test. 84 subjects (mean age 63.2; 24-89 years; n=66 males) suspected for adrenocortical insufficiency underwent an ACTH test. Patients were divided based on peak serum cortisol into hypocortical group with cortisol <500 nmol/l and to reference group cortisol >500 nmol/l. Median serum cortisol levels in reference gr oup were 445, 766, and 902 nmol/l at 0, 30, and 60 minutes, respecti vely, and in hypocortical group were 256, 394, and 453 nmol/l. Median salivary cortisol levels were 19.02, 40.02, and 62.1 nmol/l in reference group, and 9.60, 14.08, and 13.28 nmol/l in hypoco rtical group. Obtained values showed good correlation between serum and salivary cortisol (p<0.0001). The percentage of explained variability R 2 (coefficient of determination for linear model) representing a measure of agreement betwee n experimental values and predictions for repeated measur es ANOVA, was significantly higher (p=0.021) for serum cortisol (R 2 =93.4 %) when compared to the salivary cortisol (R 2 =89.3 %). A stronger discriminating power of serum versus salivary cortisol suggests that it seems to be slightly, but statistically significantly more appropriate marker of adrenocortical reserve in ACTH test., M. Kosák ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Normal pressure hydrocephalus (NPH) is one of a few treatable conditions of cognitive decline affecting predominately elderly people. Treatment, commonly based on the ventriculoperitoneal shunt insertion, leads to a partial or complete correction of patient's state, although its effect does not unfortunately always last. The aim of our study was to observe the changes of homocysteine and selected steroids and neurosteroids and follow-up the patients with respect to the duration of the NPH-related dementia improvement. The cerebrospinal fluid and plasma levels of cortisol, cortisone, dehydroepiandrosterone (DHEA), 7α-hydroxy-DHEA, 7β-hydroxy-DHEA, 7-oxo-DHEA, 16α-hydroxy-DHEA (all LC-MS/MS), DHEA-sulphate (DHEAS) (radioimmunoassay) and homocysteine (gas chromatography) were determined in NPH-diagnosed subjects before, during and 6, 12 and 24 months after shunt insertion. The cognitive functions ameliorated after shunt insertion and remain improved within 2 years. Changes in cerebrospinal fluid DHEAS, DHEA and its ratio, cortisone/cortisol and 16α-hydroxy-DHEA and plasma DHEAS, 7β-hydroxy-DHEA, cortisone/cortisol and homocysteine were found. Mentioned changes may contribute to the clarification of NPH pathogenesis. Altered neurosteroids levels are possible indicators to be utilized in the follow-up of NPH subjects. Moreover, plasma homocysteine may serve as an early indicator of NPH-related dementia., L. Sosvorova, M. Mohapl, M. Hill, L. Starka, M. Bicikova, J. Vitku, R. Kanceva, J. Bestak, R. Hampl., and Obsahuje bibliografii