Increased homocysteine levels in serum are typical features of neurodegenerative brain diseases including hydrocephalus. The most frequent therapeutic approach consists of the insertion of a shunt, connecting the brain ventricles to an alternative drainage site. To decide whether the patient should undergo this, the lumbar drainage test is usually carried out to distinguish patients who can benefit from the shunt insertion. In searching for other potential biochemical markers for shunt indication we determined homocysteine levels in CSF during the lumbar drainage test. Homocysteine in CSF was measured during the 5-day lumbar drainage test in 27 patients with normal-pressure hydrocephalus (NPH) and in 25 patients with excluded hydrocephalus. A novelized gas chromatography method with flame ionization detection (GC-FID) was developed and evaluated. During the first two days of lumbar drainage, the levels of CSF homocysteine in NPH patients were significantly higher compared to the controls, while on the fifth day, the homocysteine levels in patients with hydrocephalus reached the level of controls. Determination of CSF homocysteine in patients with confirmed or suspected hydrocephalus may serve as an independent marker for deciding on their further treatment strategy., L. Sosvorová, J. Bešťák, M. Bičíková, M. Mohapl, M. Hill, J. Kubárová, R. Hampl., and Obsahuje bibliografii
To determine whether acutely-induced supraphysiological hyperinsulinemia influences brain metabolism in patients with type 1 diabetes (D) and healthy controls (C) as detected by MR Spectroscopy. Group D consisted of 4 patients with the average duration of diabetes for 7 years. They were matched according to age, sex and BMI to 4 healthy controls. 1H MR Spectroscopy was performed with a 1.5 Tesla. Spectra were obtained from parietooccipital white matter repeatedly during a 3-h hyperinsulinemic euglycemic clamp with 2 mU.kg-1.min-1. In group D, significantly lower basal concentrations of N-acetylaspartate (p=0.02), choline (p=0.03), creatine (p=0.002) and inositol (p=0.007) were detected compared to C. After the induction of hyperinsulinemia, concentrations of choline, creatine, GABA, inositol, lactate, NAA and composite signal glutamate + glutamine (Glx) stayed stable. The detection of glucose signal is less realiable at 1.5 Tesla but we registered the alteration in glucose concentration (p=0.003) in the whole group. Originally sightly elevated glucose concentration in D decreased on the contrary to the increase of originally lower glucose level in C. In conclusions, brain metabolism was altered in D. Short term supraphysiological euglycemic hyperinsulinemia induced changes in the concentration of brain glucose in both C and D., S. Kratochvílová, A. Škoch, M. Dezortová, E. Švehlíková, M. Hill, J. Brunová, M. Hájek, T. Pelikánová., and Obsahuje bibliografii
The aim of this study was to investigate the effect of 7-oxo-DHEA (dehydroepiandrosterone) on the serum levels of steroid sexual hormones, gonadotropins, lipids and lipoproteins in men. 7-oxo-DHEA was applied onto the skin as a gel to 10 volunteers aged 27 to 72 years for 5 consecutive days. The single dose contained 25 mg 7-oxo-DHEA. Serum concentrations of testosterone, estradiol, cortisol, androstenedione, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin (SHBG), total cholesterol, HDL- and LDL-cholesterol, triglycerides, apolipoprotein A-I and B and lipoprotein(a) were measured before the beginning and shortly after the end of the steroid application. After the treatment, we noted the following significant changes: a decline of testosterone and estradiol levels, increase of LH, HDL-cholesterol and apolipoprotein A-I levels. The decrease of total cholesterol levels was of the borderline significance. A slight but significant increase was found in apolipoprotein B and lipoprotein(a). The most expressive was the fall of the atherogenic index. We suggest that the gel containing 7-oxo-DHEA might be a suitable drug for improving the composition of the steroid and lipid parameters in elderly men., J. Šulcová, M. Hill, Z. Mašek, R. Češka, A.Nováček, R. Hampl, L. Stárka., and Obsahuje bibliografii
In order to ascertain the kinetics of absorption and metabolism of transdermally administered dehydroepiandrosterone (DHEA), 10 men 29-72 years old (mean 52.4±14.5) received 50 mg DHEA/day in a gel applied onto the skin of the abdomen for 5 consecutive days. The objective was to establish the extent to which DHEA influences the levels of gonadotropins, sex hormone-binding globulin and lipids. It was found that DHEA is well absorbed and rapidly metabolized to its sulfate (DHEAS), androstenedione, and consequently to testosterone and estradiol. The DHEA levels that markedly increased after the first doses gradually declined already during the application, and this decline proceeded even after it was discontinued, reaching levels significantly lower than the original ones. On the other hand, the levels of DHEA metabolites (with the exception of DHEAS) rose during the application and reached values significantly higher than the basal ones within 5 weeks. This effect was accompanied by significantly decreased levels of LH. The serum levels of lipids, namely of cholesterol (both HDL and LDL cholesterol), triglycerides, apolipoproteins A-I and B and lipoprotein(a) after DHEA application were not changed significantly, and the atherogenic index (AI) remained unaltered. However, some correlations between hormones and lipids were found. Negative correlations concerned the following indices: DHEA/Lp(a); DHEAS/cholesterol; DHEA, DHEAS, testosterone/TG; testosterone/AI. On the other hand, LH, FSH/cholesterol, FSH, SHBG/LDL cholesterol, FSH/Apo B, Lp(a) correlated positively. It can be concluded that transdermal short-time application of DHEA results in a decrease of endogenous DHEA after finishing the treatment, with a parallel marked increase in the levels of sex hormones. Using this application protocol, exogenous DHEA neither altered the lipid spectrum, nor did it influence the atherogenic index., J. Šulcová, M. Hill, R. Hampl, Z. Mašek, A. Nováček, R. Češka, L. Stárka., 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
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
Postpartum depression affects 10-15 % women after childbirth. There is no currently generally accepted theory about the causes and mechanisms of postpartum mental disorders. The principal hypothesis concerns the association with sudden changes in the production of hormones affecting the nervous system of the mother and, on the other hand, with the ability of receptor systems to adapt to these changes. We observed changes in steroidogenesis in the period ar ound spontaneous delivery. We collected three samples of maternal blood. The first sampling was 4 weeks prior to term; the second sampling was after the onset of uterine contractions (the beginning of spontaneous labour); the third sampling was during the third stage of labour (immediately after childbirth). Additionally, we collected mixed umbilical cord blood. The almost complete steroid metabolome was analyzed by gas chroma tography-mass spectrometry followed by RIA for some steroids. Mental changes in women in the peripartum period were observed using the Hamilton Depression Rating Scale. The local Ethics Committee approved the study. We found already th e changes in androgens levels correlating with postpartum mood disorders four weeks prior to childbirth. The strongest correlations between steroid and postpartum mood change were found in venous blood samples collected from mothers after childbirth and from umbilical cord blood. The main role played testosterone, possibly of maternal origin, and estrogens originating from the fetal compartment. These results suggest that change s in both maternal and fetal steroidogenesis are involved in the development of mental changes in the postpartum period. Descriptions of changes in steroidogenesis in relation to po stpartum depression could help clarify the causes of this disease, and changes in some steroid hormones are a promising marker of mental changes in the postpartum period., A. Pařízek, M. Mikešová, R: Jirák, M. Hill, M. Koucký, A. Pašková, M. Velíková, K. Adamcová, M. Šrámková, H. Jandíková, M. Dušková, L. Stárka., and Obsahuje bibliografii