Estradiol, obesity and hypogonadism.

Obesity increases the incidence of hypogonadism in men, and hypogonadism in turn plays a role in obesity. One of the first mechanisms proposed to explain this was a hypothesis based on the principle that obese men have higher estrogen levels, and that increased estrogens provide feedback to the hypothalamic-pituitary-testicular axis, reducing the secretion of gonadotropins and leading to a decrease of overall testosterone levels. This concept has since been questioned, though never completely disproven. In this study we compared hormone levels in three groups of men with differing BMI levels (between 18-25, 25-29, and 30-39), and found correlations between lowering overall testosterone, SHBG and increased BMI. At the same time, there were no significant changes to levels of free androgens, estradiol or the gonadotropins LH and FSH. These findings are in line with the idea that estrogen production in overweight and obese men with BMI up to 39 kg/m(2) does not significantly influence endocrine testicular function.

Are there sex differences in the reaction of undercarboxylated osteocalcin to hypoglycemia?

There has been increasing evidence in recent years for the hypothesis of bones as endocrine organs. Osteocalcin, long considered just a marker of new bone formation, is now seen as the first hormone produced by bones, and seems to be associated with regulating glucose metabolism and reproduction. The aim of this work was to monitor changes of osteocalcin in reaction to hypoglycemia, and determine if there are differences in such reactions between the sexes. The study included 61 healthy probands with physiological calciophosphate metabolism (30 men and 31 women). We applied to each of them an insulin tolerance test, and then monitored levels of undercarboxylated osteocalcin and reactions to hypoglycemia at regular time intervals. We found differences in the reaction to hypoglycemia between the sexes. In men there was a significant decline in undercarboxylated osteocalcin between the 30 and 40 min (p<0.0015), which reflects a reaction to a glycemic decline between 25-30 min, followed by reversal. Low undercarboxylated osteocalcin in men lasted up to 90 min, after which they returned to levels before the test. In women we did not find any significant changes in undercarboxylated osteocalcin levels. Changes in undercarboxylated osteocalcin induced by hypoglycemia indicate a relationship between bones and glucose metabolism. There was an interesting difference between the sexes. However, a definitive conclusion about the role of osteocalcin in human metabolism will require numerous future studies.

Can the gold standard be beaten? How reliable are various modifications of the Synacthen test compared to the insulin tolerance test.

Criteria for the evaluation of the insulin tolerance test (ITT) and Synacthen test are still a matter of debate. The objective of the study was to make a comparison of serum and salivary cortisol during four stimulation tests. Sixty four healthy volunteers underwent the ITT, the Synacthen test with 1 (LDST), 10 (MDST) and 250 (HDST) microg dose of ACTH. Maximum serum cortisol response was observed at the 90 min of the ITT (49 %), HDST (89 %) and MDST (56 %) and at the 40 min of the LDST (44 %). Results expressed as 95 % confidence intervals: 408.0-843.6 and 289.5-868.1 nmol/l in the IIT at 60 and 90 min. In the HDST and the MDST serum cortisol reached the maximum at 90 min 542.6-1245.5 and 444.2-871.3 nmol/l. Levels of salivary cortisol followed the same pattern as serum cortisol. Salivary cortisol reached the maximum response in the HDST and the MDST at 90 min and at 40 min in the LDST. We confirmed good reliability of all tests with respect to timing of response and maximum response compared to the ITT. We proved that the MDST test can provide the similar response in serum cortisol to the HDST. Measuring either salivary cortisol or ACTH levels did not provide any additional benefit then measuring serum cortisol by itself.

Response of cortisol metabolites in the insulin tolerance test and Synacthen tests.

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.

Effects of smoking cessation on hormonal levels in men.

Chronic smoking can cause imbalance in endocrine homeostasis and impairment of fertility in both sexes. The male reproductive system is more resilient, still the literature provides conflicting results about the influence of smoking on the steroid hormone levels. The data about smoking cessation are limited; there has not yet been a study primarily focused on changes in steroids levels. In our study, we analyzed levels of testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), cortisol and sex hormone-binding globulin (SHBG) in male smokers and during smoking cessation. Monitored analytes were determined by RIA. The free testosterone index was calculated. Basal samples of men successful and unsuccessful in smoking cessation did not differ and monitored hormones could hardly predict success of smoking cessation. After one year without smoking, a significant BMI increase and SHBG decrease in former smokers was observed. The decrease in total testosterone was non-significant. Changes in SHBG and testosterone did not correlate with BMI, presumably due to the direct effect of smoking cessation.

The differences between aromatizable and non-aromatizable androgens in relation to body composition and metabolic syndrome risk factors in men.

The relationships between the parameters of metabolic syndrome and non-aromatizable metabolites of testosterone have been discussed in literature. Some papers describe these metabolites as one of the possible causes of male-type obesity. On the contrary, other studies show a protective influence of dihydrotestosterone on visceral obesity. The aim of this study to analyse the relationship between anthropometric parameters, lipid spectrum, glycemia and the level of endogenous testosterone and dihydrotestosterone, and to compare the effects of these androgens. Our population-based study involved 232 healthy men ranging from 20 to 78 years with BMI 18 to 39 kg/m(2). Serum testosterone, dihydrotestosterone and sex hormone binding globulin SHBG levels, lipid spectrum, glucose metabolism parameters were measured and the oral glucose tolerance test was carried out in all subjects. Their anthropometric parameters (weight, height, waist, hips, waist-to-hip ratio, 14 skin folds) and body composition parameters were determined and calculated by the Antropo program. Multiple regression analysis showed a correlation between hormonal levels, esp. of testosterone and dihydrotestosterone, and the anthropometric data, lipid spectrum and parameters of glucose regulation. Low testosterone and/or dihydrotestosterone was correlated to a higher body-mass index, fat content, waist diameter, total-, HDL-, LDL-cholesterol and triglycerides, fasting glucose, insulin resistance and lower muscle and bone mass. In addition, statistical analysis using multivariate regression with reduction in dimensionality did not discover any striking difference between aromatizable and non-aromatizable androgens in their association to lipid and glucose metabolism parameters in healthy, normosthenic men. In conclusion, the association of endogenous testosterone and dihydrotestosterone to anthropometric data, lipid spectrum and insulin sensitivity are of the same quality; however, the effect of the circulating levels of dihydrotestosterone is quantitatively smaller.

Chronic cigarette smoking alters circulating sex hormones and neuroactive steroids in premenopausal women.

Chronic smoking alters the circulating levels of sex hormones and possibly also the neuroactive steroids. However, the data available is limited. Therefore, a broad spectrum of free and conjugated steroids and related substances was quantified by GC-MS and RIA in premenopausal smokers and in age-matched (38.9+/-7.3 years of age) non-smokers in the follicular (FP) and luteal phases (LP) of menstrual cycle (10 non-smokers and 10 smokers, in the FP, and 10 non-smokers and 8 smokers in the LP). Smokers in both phases of the menstrual cycle showed higher levels of conjugated 17-hydroxypregnenolone, 5alpha-dihydroprogesterone, conjugated isopregnanolone, conjugated 5alpha-pregnane-3beta,20alpha-diol, conjugated androstenediol, androstenedione, testosterone, free testosterone, conjugated 5alpha-androstane-3alpha/beta,17beta-diols, and higher free testosterone index. In the FP, the smokers exhibited higher levels of conjugated pregnenolone, progesterone, conjugated pregnanolone, lutropin, and a higher lutropin/follitropin ratio, but lower levels of cortisol, allopregnanolone, and pregnanolone. In the LP, the smokers exhibited higher levels of free and conjugated 20alpha-dihydropregnenolone, free and conjugated dehydroepiandrosterone, free androstenediol, 5alpha-dihydrotestosterone, free and conjugated androsterone, free and conjugated epiandrosterone, free and conjugated etiocholanolone, 7alpha/beta-hydroxy-dehydroepiandrosterone isomers, and follitropin but lower levels of estradiol and sex hormone binding globulin (SHBG) and lower values of the lutropin/follitropin ratio. In conclusion, chronic cigarette smoking augments serum androgens and their 5alpha/beta-reduced metabolites (including GABAergic substances) but suppresses the levels of estradiol in the LP and SHBG and may induce hyperandrogenism in female smokers. The female smokers had pronouncedly increased serum progestogens but paradoxically suppressed levels of their GABA-ergic metabolites. Further investigation is needed concerning these effects.

The role of non-aromatizable testosterone metabolite in metabolic pathways.

Dihydrotestosterone (DHT) originates via irreversible reduction of testosterone by catalytic activity of 5alpha-reductase enzyme and it is demonstratively the most effective androgen. Androgens influence adipose tissue in men either directly by stimulation of the androgen receptor or indirectly, after aromatization, by acting at the estrogen receptor. DHT as a non-aromatizable androgen could be responsible for a male type fat distribution. The theory of non-aromatizable androgens as a potential cause of a male type obesity development has been studied intensively. However, physiological levels of DHT inhibit growth of mature adipocytes. In animal models, substitution of DHT in males after gonadectomy has a positive effect on body composition as a testosterone therapy. Thus, DHT within physiological range positively influences body composition. However, there are pathological conditions with an abundance of DHT, e.g. androgenic alopecia and benign prostatic hyperplasia. These diseases are considered as risk factors for development of metabolic syndrome or atherosclerosis. In obese people, DHT metabolism in adipose tissue is altered. Local abundance of non-aromatizable androgen has a negative effect on adipose tissue and it could be involved in pathogenesis of metabolic and cardiovascular diseases. Increased DHT levels, compared to physiological levels, have negative effect on development of cardiovascular diseases. Difference between the effect of physiological and increased level brings about certain paradox.

[Midterm results aortic valve replacement with allograft]. / Strednedobé výsledky implantací aortálního alograftu.

INTRODUCTION: Aortic allograft implantation into the aortic position in adults is standard procedure with some controversary. The most popular indication is bacterial endocarditis. We would like to present our midterm results. RESULTS: We implanted 61 allografts in 60 patients (between 10/2002 and 04/2008). Men were 46 (76.8%) and average age was 57 +/- 10.76 year. 30 days mortality was 9 people (15.0%, all with bacterial endocarditis). Late mortality 1 man (1.6%). Follow up 1-66 months, average 39.18 SD +/- 14.3 months, median 42 months. CONCLUSION: Implantation of aortic allograft into the aortic position is standard procedure with good midterm results. Relative high early mortality is dependent on preoperative status in patiens with acute bacterial endocarditis--all early death people were people with acute bacterial endocarditis and minimally one vital organ severe dysfunction.

[Aortic allograft (homograft) for the treatment of valvular disorders in adults with focus on treatment of infective aortic valve endocarditis]. / Aortální alograft (homograft) v lécbe chlopennich srdecních vad dospelých s durazem na lécbu infekiní endokarditidy aortální chlopne.

Still after 40 years of heart valve prostheses intensive development ideal valve substitute still does not exist. Aortic allograft represents one alternative which could be used for aortic and/or pulmonary valve replacement. This type of biological heart valve prosthesis is being currently discussed from the point of view of Tissue Banking, as well as from clinical aspects--e.g. surgical implantation technique and long term results. Live issue remains particularly the aortic allograft implantation into the aortic position. The authors discuss the aortic allograft role in the aortic valve infectious endocarditis treatment, which was widespread worldwide and accepted. Aortic allograft implantation is considered as a method of choice in that particular indication, especially in prosthetic aortic valve endocarditis and in left ventricle outlet tract destruction cases. The method is considered to be more technically demanding than routine heart valve surgery (heart valve replacement by means of mechanical or commercial biological prostheses), but literary and authors own experience in that particular group of patients looks encouraging. Aortic allografts permanent supply in our country is secured.

[Principle and importance of using the array CGH in hematooncology]. / Princip a význam metody arrayCGH v hemato-onkologii.

Identification of chromosomal changes and variation in DNA copy number allows us to understand pathogenesis of tumors. To the frequently diagnosed chromosomal changes belong acquired gains and losses of chromosomal regions carring genes involved in cellular proliferation and differentiation as well as oncogenes and tumor suppressor genes. The determination of gene changes is limited by techniques used for their identification. The introduction of genom-wide microarray technology, resolution has rapidly increased. Array comparative genomic hybridization (arrayCGH) offers higher resolution for genome-wide detection of chromosomal alteration and it is able to analyze hundreds to thousands of genes presented on microarray in one experiment. The aim of this study was to perform arrayCGH technology and to stress its value for the identification of chromosomal imbalances in hematological malignancies.

High incidence of unbalanced chromosomal changes in mantle cell lymphoma detected by comparative genomic hybridization.

Comparative genomic hybridization (CGH) was carried out in 30 mantle cell lymphoma (MCL) patients at the time of diagnosis. CGH results were supported by conventional cytogenetics (CC), FISH, molecular genetic PCR methods and 2 patients were examined by array CGH. Using all cytogenetic, molecular cytogenetic and PCR methods, chromosomal changes were detected in 28 (93%) patients. Using CGH, unbalanced chromosomal changes were detected in 24 (80%) cases. The most frequent aberrations were losses of 1p (8 cases), 8p (10 cases), 9q (6 cases), 11q (11 cases), 13q (10 cases) and 17p (9 cases), and gains of chromosome 3 and 3q (12 cases) and 8q (7 cases). Total number of 60 gains and 116 losses were detected. The primary chromosomal change t(11;14) was detected using FISH and/or PCR in 20 (66.6%) patients, and in 9 of them, the breakpoint was determined using PCR in the major translocation cluster (MTC). The evaluation of the frequencies of CGH changes in groups of patients with and without t(11;14) revealed the differences only in losses 6q and 9q, which were only found in patient with t(11;14). An important result was obtained using array CGH method. In a patient without the primary t(11;14), the gain of CCND1 gene was found. Our results show high heterogeneity of the additional chromosomal changes in MCL cases, which involved specific chromosomal subregions. We did not confirm the importance of subdividing of MCL cases with and without t(11;14). Also, statistical significance in survival rates between both subgroups was not confirmed.

Assessment of occupational doses from internal contamination with 241Am.

A group of workers with occupational intakes of 241Am, which occurred a long time ago, has been followed for some time. Results of in vivo measurement and bioassay of excreta are compared with the values predicted by the ICRP Publication 78 model. The observed skeletal content is, as a rule, higher than the predicted one. The ratio of excreted activity in urine to that in faeces is in very good agreement with the model prediction. Another group of workers from a waste management department, who were internally contaminated in July 2001, has also been followed. In some cases, there is quite a large difference in calculated intake between excretion by urine and that by faeces. The contaminant was presumably the same as that in the group of workers with old intakes, but its physical and chemical form could be influenced by a fixating lacquer used to prevent the spread of contamination.

[Is a bioprosthesis with a rigid stent a good choice for aortic valve replacement in elderly patients?]. / Je bioprotéza s rigidním stentem dobrou volbou pro náhradu aortální chlopne u starsích pacientu?

BACKGROUND: Either stented or stentless bioprostheses can be used for aortic valve replacement (AVR) in aged patients. However the choice of the valve type remains controversial. The implantation technique of the stentless valves is more complex but the haemodynamic performance supposed to be superficial to the stented ones. The aim of the study was to review our experience with stented bioprostheses implanted in the last year. MATERIAL AND METHODS: The study reviews retrospectively 35 patients who underwent AVR with Biocor fy St Jude Medical from May 2000 to May 2001. The mean age was 73 years (65-81). Associated procedures were CABG in 17, aortoplasty in 3 and Bentall procedure in 1. Thirty-two patients had aortic stenosis, the mean preoperative gradient was 44.2 mmHg. Nineteen implanted valves were 23 mm and smaller in diameter. All patients were examined by a cardiologist (including ECHO) one month after surgery. RESULTS: There was no early mortality (30 days) and no sign of structural valve deterioration or valve thrombosis. Mean hospital stay was 10.2 days (5-30). Mean postoperative gradient one month after surgery was 14.1 mmHg (6-24). CONCLUSIONS: The AVR with a stented bioprosthesis is a standard procedure with excellent results, the postoperative gradient is comparable to the gradient of the stentless valves.