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Martin Hill

Publications and source records attributed to Martin Hill.

At least 37 records · Page 2Linked to original sources
PubMed2004

Simultaneous determination of dehydroepiandrosterone, its 7-hydroxylated metabolites, and their sulfates in rat brain tissues.

A method is described for simultaneous assessment of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), and their 7-hydroxylated metabolites in cortex and subcortex of the rat brain. The procedure for determination of unconjugated steroids and DHEAS involved diethyl ether extraction of the homogenized tissue, solvent partition of the dry extract, and final quantification by specific radioimmunoassays. In addition, determination of 7-hydroxy-dehydroepiandrosterone sulfates required solvolysis, followed by high-performance liquid chromatography for separation of 7-hydroxylated metabolites from their precursor. The losses during this process were monitored by measurement of spiked radioactivity of [(3)H]testosterone or [(3)H]dehydroepiandrosterone sulfate. The content of dehydroepiandrosterone sulfate in both brain tissues was of the order of ten(s) nmol/g tissue irrespective its type (cortex or subcortex), while concentrations of other steroids were about 10 times lower in both tissues. In contrast to the ratio of sulfated/unconjugated DHEA, the levels of unconjugated 7-hydroxylated metabolites and their sulfates were close to each other. The reproducibility of the method with respect to coefficients of variation varied from 12 to 25%. An age-related decrease of sulfated dehydroepiandrosterone in the cortex of animals was also observed.

Age Factors↗
PubMed2004

Insulin sensitivity in women with polycystic ovary syndrome.

The aim of our study was to compare insulin sensitivity in lean and obese European polycystic ovary syndrome (PCOS) women with lean healthy women. We performed the euglycemic hyperinsulinemic clamp in 83 women with PCOS [53 lean with body mass index (BMI) of 21.5 +/- 1.8 kg/m2 and 30 obese with BMI of 29.6 +/- 3.7 kg/m2] and in 15 healthy women with BMI of 21.6 +/- 1.8 kg/m2 to determine glucose disposal (M) and the insulin sensitivity index (ISI). Statistical evaluation was done using Kruskal-Wallis ANOVA followed by Kruskal-Wallis multiple-comparison z-value test. The basal blood glucose was significantly higher in lean and obese PCOS women than in controls (P < 0.02). Fasting insulin was significantly higher in both lean and obese PCOS women than in controls (P < 0.000001). Obese PCOS women were more insulin resistant than controls (P < 0.02 for M and P < 0.0008 for ISI); lean PCOS women did not differ from controls in M or ISI. Posthepatic insulin delivery was significantly higher in both lean and obese PCOS women compared with controls (P < 0.000008). We conclude that lean PCOS women are not more insulin resistant than healthy controls. Insulin hypersecretion, on the other hand, is present even in lean PCOS women.

Adult↗
PubMed2004

New methodology of influential point detection in regression model building for the prediction of metabolic clearance rate of glucose.

Identifying outliers and high-leverage points is a fundamental step in the least-squares regression model building process. The examination of data quality involves the detection of influential points, outliers and high-leverages, which cause many problems in regression analysis. On the basis of a statistical analysis of the residuals (classical, normalized, standardized, jackknife, predicted and recursive) and diagonal elements of a projection matrix, diagnostic plots for influential points indication are formed. The identification of outliers and high leverage points are combined with graphs for the identification of influence type based on the likelihood distance. The powerful procedure for the computation of influential points characteristics written in S-Plus is demonstrated on the model predicting the metabolic clearance rate of glucose (MCRg) that represents the ratio of the amount of glucose supplied to maintain blood glucose levels during the euglycemic clamp and the blood glucose concentration from common laboratory and anthropometric indices. MCRg reflects insulin sensitivity filtering-off the effect of blood glucose. The prediction of clamp parameters should enable us to avoid the demanding clamp examination, which is connected with a higher load and risk for patients.

Algorithms↗
PubMed2004

Plasma levels of 7-hydroxylated dehydroepiandrosterone (DHEA) metabolites and selected amino-thiols as discriminatory tools of Alzheimer's disease and vascular dementia.

OBJECTIVE: The early differential diagnosis of Alzheimer's disease (AD) remains still problematic. We developed a laboratory test enabling us to distinguish patients with AD from those with vascular dementia (VD) and healthy subjects. METHODS: The AD group consisted of 22 women and 18 men. The VD group consisted of 16 women and 8 men. Age-matched controls consisted of 12 women and 9 men. Plasma pregnenolone sulfate (PregS), dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) were determined by radioimmunoassay. 17-Hydroxypregnenolone (17Preg) and 7-hydroxylated metabolites of DHEA (7alphaDHEA, 7betaDHEA) were determined by radioimmunoassay after separation by high performance liquid chromatography (HPLC). Homocysteine (Hcy), cysteine (Cys), cysteinylglycine (Cysgly) and glutathione (GSH) were measured by HPLC. RESULTS: The ANOVA results of significant between-group differences were as follows: The PregS and the 17-Preg and DHEAS levels were independent from the diagnosis. The 7alphaDHEA levels significantly depended on the sex (p < 0.05) and diagnosis (p < 0.01). Amino-thiols were influenced by the diagnosis (p < 0.01, p = 0.0541, p < 0.01 and p = 0.0536 for Cys, Hcy, Cysgly and GSH, respectively). Using a stepwise backward regression analysis, the following parameters were obtained: X = 11.5 + 4.03 x sex +1.09 x Hcy + 0.190 x PregS - 4.76 x DHEAS + 3.00 x DHEA - 34.3 x 77alphaDHEA - 0.885 x Cysgly from which P-value as a discriminator was calculated according to the formula: P = 1/(1 + e(-x)). Then, for P > 0.5, a subject was considered as AD-positive (with 89% correct prediction). DISCUSSION: The opportunity of early differential diagnosis of AD should help physicians to use suitable treatment for retardation of pathological processes.

17-alpha-Hydroxypregnenolone↗
PubMed2003

Synthesis of two new haptens of 16alpha-hydroxydehydroepiandrosterone (3beta,16alpha-dihydroxyandrost-5-en-17-one).

Synthetic routes leading to 19E and 7Z O-(carboxymethyl)oximes derived from 16alpha-hydroxydehydroepiandrosterone were developed using two independent methods for introduction of the 16alpha-hydroxy group. Firstly, the oxime moiety was built, and then, either epoxidation of the enol acetate followed by the boron trifluoride mediated rearrangement or alkaline hydrolysis of the corresponding alpha-bromide in aqueous N,N-dimethylformamide were employed. The last step in both methods was removal of the protecting groups, which consisted of acid deprotection of the acetates and gentle alkaline hydrolysis of the methyl ester. Final haptens were designed as components for immunoanalytical kits.

Dehydroepiandrosterone↗
PubMed2003

Immunomodulatory cytokines in human seminal plasma correlate with immunomodulatory steroids.

7alpha-Hydroxy-dehydroepiandrosterone and its 7beta-hydroxyepimer, which act as local immunomodulatory agents, dehydroepiandrosterone, cortisol, and major androgens, together with four cytokines-interleukins 2, 4, 10, and IFN-gamma, reflecting the activity of TH1 or TH2 cells present in semen, were measured in seminal plasma from 35 male donors. Cortisol, dehydroepiandrosterone, its sulfate, 7-hydroxy-dehydroepiandrosterone epimers, testosterone, and estradiol were also measured in their blood serum. Steroids and interleukins in semen as well as serum steroids and seminal interleukins were mutually correlated to find out whether a relationship between immunomodulatory steroids and cytokines influencing the immune environment does exist. A highly significant (P<0.001) positive correlation was found between seminal 7beta-hydroxy-dehydroepiandrosterone and IFN-gamma, while a negative correlation was found between cortisol and IL-10. Highly significant positive correlations were also found between serum 7alpha-hydroxy-dehydroepiandrosterone and seminal IFN-gamma and between serum 7beta-hydroxy-dehydroepiandrosterone and seminal IL-2, while a negative correlation was found between serum dehydroepiandrosterone and seminal IL-10. Different and in some instances, even contradictory findings concerning the influence of dehydroepiandrosterone and cortisol on TH1 and TH2 cytokines were observed in seminal plasma as compared to those found by others in serum. The differences can be ascribed to the different environments of mucosal and systemic immunity. Correlations between the levels of steroids and cytokines in seminal plasma did not always correspond to the correlations between given cytokines and hormones in sera. The results, however, are in agreement with our recent finding of an autonomous production of these steroids in the male reproductive tract.

Adult↗
PubMed2003

Assessment of the mean-value of 17-hydroxypregnenolone in the umbilical blood of newborns by the exploratory analysis of biochemical data.

The main aim of data analysis in biochemical metrology is the extraction of relevant information from biochemical data measurements. A system of extended exploratory data analysis (EDA) based on the concept of graphical tools for sample data summarization and exploration is proposed and the original EDA algorithm in S-Plus is available on the Internet at http://www.trilobyte.cz/EDA. To check basic assumptions about biochemical and medical data is to examine the independence of sample elements, sample normality and homogeneity. The exact assessment of the mean-value and the variance of steroid levels in controls is necessary for the correct assessment of the samples from patients. Data examination procedures are illustrated by a determination of the mean-value of 17-hydroxypregnenolone in the umbilical blood of newborns. For an asymmetric, strongly skewed sample distribution corrupted with outliers the best estimate of location seems to be the median. The Box-Cox transformation improves a sample symmetry. The proposed procedure gives reliable estimates of a mean-value for an asymmetric distribution of 17-hydroxypregnenolone when the arithmetic mean can not be used.

17-alpha-Hydroxypregnenolone↗
PubMed2003

Division of lymphatic vessels at varicocelectomy leads to testicular oedema and decline in testicular function according to the LH-RH analogue stimulation test.

OBJECTIVES: To study the andrological outcome of the division of testicular lymphatic vessels at varicocelectomy in children and adolescents. METHODS: Testicular size and basal and stimulated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) values were determined prospectively in 86 patients with left unilateral varicocele grades II-III. 22 patients underwent lymphatic non-sparing surgery (LNS group), 10 of them with artery sparing (LNS/AS) and 12 without artery sparing (LNS/ANS), 23 patients underwent lymphatic sparing repair (LS group) and 41 patients were treated conservatively (NT group). RESULTS: The LNS group demonstrated significantly greater left testicular enlargement at six weeks and one year following repair, left testicular hypertrophy developed in 31.8% and hydrocele in 22.7% of patients. Marked oedema of intertubular tissue and a varying degree of tubular injury was observed in boys surgically treated for hydrocele. In the LS group, neither hypertrophy nor hydrocele developed postoperatively, the LH stimulated values were lower than in LNS/ANS group (p<0.05) and the NT group (p<0.04), the FSH stimulated values were lower than in the LNS/ANS group (p<0.001). CONCLUSIONS: Division of lymphatic vessels at varicocelectomy is associated with an excessive increase in testicular volume due to oedema, and with a reduced testicular function according to higher LH and FSH stimulated values. Preservation of lymphatics is strongly advised in varicocelectomy in adolescents to ensure better andrological outcome.

Adolescent↗
PubMed2003

The content of four immunomodulatory steroids and major androgens in human semen.

Seminal fluid fulfils a dual role: it provides optimal conditions for fertilization and protects male germ cells from infections. Besides both major sexual hormones and cortisol it contains a considerable amounts of dehydroepiandrosterone (DHEA), known to counteract the excessive actions of glucocorticoids. From this point of view of importance may be our recent finding of both 7-hydroxy-dehydroepiandrosterone epimers (7-OH-DHEA) in semen, believed to be in some instances the locally active immunoprotective agents. The concentrations of these steroids were of the same range or even higher than in blood. Here further data on 7-OH-DHEA in semen, along with other relevant steroid hormones, are given in 79 samples, either from healthy males or from patients with various sexual disorders. A method has been developed enabling us a simultaneous determination of DHEA, 7-OH-DHEA epimers, testosterone, dihydrotestosterone and cortisol in seminal fluid. It was based on ether extraction, solvent partition and HPLC separation, followed by specific radioimmunoassays in the respective fractions. In addition, the steroids were measured in serum and the concentrations in both fluids were compared. The concentrations of 7-OH-DHEA in seminal fluid varied from 1.8 to 15.7 nmol/l, while those of DHEA were about five times higher.

Adult↗
PubMed2003

Interpretation of sex hormone-binding globulin levels in thyroid disorders.

Sex hormone-binding globulin (SHBG) levels were followed in three groups of female subjects to evaluate interrelationships between its levels and parameters characterizing thyroid function. In the first part of the study the data from 201 patients with thyroid and other endocrine dysfunctions were grouped according to SHBG or basic laboratory parameters of thyroid function (thyrotropin, free thyroxine). Particular attention was paid to the presence of antithyroid antibodies (against thyroglobulin or thyroid peroxidase). Analysis of covariance revealed that SHBG changes were significant only in hyperthyroidism, and were not influenced by the presence of antibodies. Age was a minor factor influencing SHBG levels, in contrast to thyroid status. In a well-defined group of 16 females with severe hypothyroidism after total thyroidectomy because of thyroid cancer the low SHBG levels increased significantly to physiologic values after reaching normal thyroid function, irrespective of contraceptive use. In the final part of the study SHBG levels were correlated with the basic laboratory data, reflecting thyroid function in a sample of normal female population (129 subjects) screened for iodine deficiency in one region of the Czech Republic. After adjustment for age, the only significant positive correlation was between SHBG and free triiodothyronine.

Adolescent↗
PubMed2003

Neurosteroids: Cerebrospinal fluid levels for Alzheimer's disease and vascular dementia diagnostics.

A neurodegenerative disease such as Alzheimer's disease (AD) is associated with significantly higher dehydroepiandrosterone (DHEA) levels in cerebrospinal fluid (CSF). Because the human brain is known to transform DHEA into DHEA sulfate (DHEAS), 7 alpha-hydroxy-DHEA, 7 beta-hydroxy-DHEA, and 16 alpha-hydroxy-DHEA, it is possible that DHEA accumulation in the brain results from a decreased production of such metabolites. To test this hypothesis, we have measured and compared CSF levels of DHEA, DHEAS, 7 alpha-hydroxy-DHEA, 7 beta-hydroxy-DHEA, and 16 alpha-hydroxy-DHEA in 14 patients with AD, 12 controls, and eight patients with another common dementia, vascular dementia (VD). Results indicated that DHEAS CSF levels were significantly decreased in AD and VD (P < 0.007), whereas other metabolite levels were not significantly changed. Use of steroid level ratios, such as DHEA/(7 alpha-hydroxy-DHEA + 7 beta-hydroxy-DHEA), 7 beta-hydroxy-DHEA/DHEA, and DHEAS/DHEA ratios, resulted in significant differences between diseased and control patients (P < 0.0003, P < 0.002, and P < 0.002, respectively). In addition, the 7 alpha-hydroxy-DHEA/7 beta-hydroxy-DHEA ratio was significantly different between AD and VD (P < 0.0001) and could be used for differentiating AD from VD. These results indicate that, in AD and VD, increased DHEA levels are not neuroprotective and are neither better sulfated nor better hydroxylated at the 7 alpha, 7 beta, and 16 alpha positions than in controls. The results also suggest that, in AD and VD brains, the sulfotransferase and the cytochromes P450 responsible for the 7 alpha-, 7 beta-, and 16 alpha-hydroxylations of DHEA are either present at lower levels or transformed through natural polymorphism into less-efficient enzymes.

Aged↗
PubMed2003

Novel and traditional biomarkers of bone turnover in postmenopausal women.

Urinary markers of bone collagen degradation such as N-terminal telopeptide, deoxypyridinoline, hydroxyproline and proline-hydroxyproline dipeptide as a novel marker were measured in both morning and daily urine samples collected from 40 postmenopausal women on 10 consecutive days. In addition, osteocalcin, bone alkaline phosphatase and procollagen C-terminal propeptide were analyzed in one serum sample from each of the women. DXA densitometry was employed to differentiate between osteopenic and osteoporotic women. Spearman rank correlation, factor analysis and receiver-operating characteristics were computed to evaluate the results. The highest correlation with a single common factor was found between telopeptide assayed in daily urine, followed by the dipeptide and hydroxyproline assayed in morning urine. These markers also showed high sensitivity for the diagnosis of osteoporosis, while osteocalcin had a high sensitivity for the diagnosis of bone disease. The concentrations of telopeptide, dipeptide and osteocalcin differed significantly between the osteopenic and osteoporotic subjects. Because of the ease of non-hydrolyzed urine processing, the speed of chromatographic analysis and the negligible costs, the dipeptide assay opens new possibilities in the field.

Absorptiometry, Photon↗
PubMed2003

Plasma thiols and androgen levels in polycystic ovary syndrome.

Homocysteine is a risk factor for ischemic heart disease; similarly as is hyperlipidemia or insulin resistance, which frequently occur in women with polycystic ovary syndrome. We examined the relationships between thiols and hormonal status or insulin resistance in 40 women (aged 25.8 +/- 7 years) with polycystic ovary syndrome and in 11 controls (33 +/- 5 years). Blood levels of homocysteine, glutathione, total and high density lipoprotein (HDL)-cholesterol, triglycerides, insulin, sex hormone-binding globulin, testosterone, androstenedione, dehydroepiandrosterone sulfate, and estradiol were determined. Student's t test and Spearman correlations were computed after adjustment for body mass index (BMI) and age. Homocysteine was significantly higher in polycystic ovary syndrome patients than in the control group (10.3 +/- 2.87 vs. 8.78 +/- 2.75 micromol/l; p < 0.05). In women with polycystic ovary syndrome, there were significant positive correlations between homocysteine and androstenedione (r = 0.329; p < 0.05) and glutathione and dehydroepiandrosterone sulfate (DHEA-S) (r = 0.469; p < 0.05). We conclude that homocysteine is increased in women with polycystic ovary syndrome and is probably linked to androgen levels but not to markers of insulin resistance or with lipid metabolism.

Adolescent↗
PubMed2003

Steroids, sex hormone-binding globulin, homocysteine, selected hormones and markers of lipid and carbohydrate metabolism in patients with severe hypothyroidism and their changes following thyroid hormone supplementation.

Laboratory markers of thyroid function, selected steroid hormones, sex hormone-binding globulin (SHBG), homocysteine, prolactin, major markers of lipid- and glucose metabolism and of insular-growth hormone axes were investigated in fasting sera from 16 female patients with severe hypothyroidism after thyroidectomy because of thyroid cancer. The results obtained in severe hypothyroidism within 5-6 weeks after withdrawal of thyroid substitution therapy before control scintigraphy were compared with those obtained after correction of thyroid function. Elevated levels of homocysteine and prolactin in hypothyroidism significantly decreased after correction, while SHBG concentration increased. Correction of thyroid function led to significant changes of growth hormone and immunoglobulin F1 (decrease and increase, respectively), while insulin and proinsulin increased only insignificantly. Elevated levels of total cholesterol and triglycerides in hypothyroidism were normalized, along with a significant increase in high density lipoprotein (HDL)-cholesterol. As revealed by correlation and factor analyses, different relationships characterizing both states were found in hypothyroidism and after correction of thyroid function. A strong inverse relationship between homocysteine and free thyroid hormones confirms the effect of thyroid hormones on homocysteine metabolism. No such inverse relation was found in euthyroid state, however. Similarly, in hypothyroidism only, dehydroepiandrosterone sulfate correlated positively with immunoglobulin F1 and homocysteine and negatively with thyroid hormones and SHBG.

Adult↗
PubMed2003

Relationship of dehydroepiandrosterone and its 7-hydroxylated metabolites to thyroid parameters and sex hormone-binding globulin (SHBG) in healthy subjects.

The concentrations of four immunomodulatory steroids, namely dehydroepiandrosterone (DHEA), its sulfate and its 7-hydroxylated metabolites, and sex hormone-binding globulin (SHBG) and major laboratory parameters of thyroid function were determined in sera from 104 healthy females and 48 males, screened for iodine deficiency in one region of the Czech Republic. The mutual relationships of the laboratory parameters were investigated by using four statistical approaches: correlation analysis, principal component analysis, canonical correlation and linear model relationship. In addition to expected correlations among thyroid parameters and substrate-product relationships among the steroids, several new relationships were revealed: The only thyroid parameter tightly correlating with SHBG was free triiodothyronine. The latter hormone was also associated with one of the 7-OH-DHEA epimers, namely with 7beta-OH-DHEA. Thyroid hormones are known to possess thermogenic properties, as does another 7-oxygenated DHEA metabolite, 7-oxo-DHEA, the major metabolite of which is 7beta-OH-DHEA. It may indicate a link between the two thermogenic factors. The results should serve for further investigation of changes in the thyroid hormone concentrations, together with SHBG and dehydroepiandrosterone metabolites, under various pathological situations.

Adolescent↗
PubMed2002

Two neuroactive steroids in midpregnancy as measured in maternal and fetal sera and in amniotic fluid.

Allopregnanolone and pregnenolone sulfate, which are neuroactive steroids that differentially modulate the sensitivity of GABA(A) and NMDA receptors, were measured simultaneously in maternal and fetal sera and in amniotic fluid for the first time during the second trimester of gravidity. The study included 33 pregnant women, who underwent cordocentesis due to suspicion of fetal abnormality or alloimmunization. Allopregnanolone concentrations in maternal and fetal sera were similar and close to the previously found levels in healthy controls at 20 weeks of gestation The levels of pregnenolone sulfate in maternal serum were 2-3 times higher and in fetal serum, as much as 10-25 times higher than those found by others in the serum of healthy, non-pregnant women. A positive correlation between maternal and fetal allopregnanolone indicate similar 5alpha-reductase activities or the efficient transport of allopregnanolone between the two subjects. No correlation of pregnenolone sulfate levels between mother and fetus was found. This finding suggests the autonomous production of pregnenolone sulfate in mother and fetus.

Amniotic Fluid↗
PubMed2002

Is a Pro12Ala polymorphism of the PPARgamma2 gene related to obesity and type 2 diabetes mellitus in the Czech population?

UNLABELLED: The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor subfamily of transcription factors. PPARgamma2 plays a key role in regulation of adipocyte differentiation and energy homeostasis. Recent studies provide evidence that the Pro12Ala polymorphism is linked to obesity and type 2 diabetes mellitus, but the results are controversial and depend on ethnicity. The aim of this study was to determine allele frequencies and to study the influence of the polymorphism on biochemical and anthropometric parameters in a Czech healthy adult population, in type 2 diabetics, and in a group of obese women. RESULTS: The frequency of the Pro12Ala PPARgamma2 gene polymorphism in Czech probands is similar to other central European populations. Frequency of the Pro12Ala substitution tends to be higher in obese women and diabetics compared with controls. The fasting insulin levels in the 12Ala carriers were significantly lower within the group of diabetics even after adjustment for age, BMI, and the length of diabetes duration. In obese women, higher WHR was found in subjects with the 12Ala allele. CONCLUSIONS: This study indicates that the substitution Pro12Ala is not associated with a decreased obesity or diabetes risk in the Czech population. However, the present data show that fasting insulin concentrations are lower in diabetics with the 12Ala allele than in those without it. This finding provides evidence that the polymorphism may influence glucose homeostasis.

Adult↗