Intraindividual variability of homocysteine and related thiols concentrations in follicular fluid.

PURPOSE: To determine intraindividual variability in concentrations of homocysteine and related thiols in follicular fluids of particular follicles after ovarian stimulation and assess the differences between follicles with/or without oocytes. METHODS: HPLC-FD analysis of plasma and follicular fluid cysteine, homocysteine, cysteinylglycine and glutathione in women undergoing IVF. RESULTS: In blood plasma, the homocysteine, cysteine, and cysteinylglycine concentrations decreased significantly during stimulation with rec FSH (p<0.001). We found significant differences in concentrations of cysteine and glutathione between follicles with or without retrieved oocytes. High intraindividual variability in concentrations of thiols was determined. CONCLUSIONS: The concentration variability of thiols between single follicles is very high and we recommend mean at least from 3 follicles with/or without oocytes for characterization of each woman. It is the best to examine individual follicles for further research and analysis of fertility outcomes.

Aminothiols in human brain tumors.

BACKGROUND: Aminothiols are sulfur-containing amino acids involved in methionine metabolism. Changes in their levels play negative roles in the genesis of many diseases. These mechanisms involve direct toxicity, either on glutamate neurotransmitter receptors or cerebrovascular endothelium, and have an indirect inhibitory effect on transmethylation reactions. Oxidative stress and excitotoxicity are factors that may rise as a consequence of increased homocysteine levels in brain tissues. We discovered new information concerning concentrations of the main aminothiols in human neoplastic brain tissues. METHODS: The cytosolic fractions of 73 tissue samples from human brain tumors were used for the determination of total homocysteine, total cysteine and methionine levels. Gas chromatography with flame ionization detection after reduction of disulfide bonds was the method used. RESULTS: Average concentrations of the aminothiols examined were as follows: total homocysteine, 0.58-1.51 nmol/mg; methionine, 1.16-2.07 nmol/mg; and total cysteine 5.08-7.82 nmol/mg of total protein. Significantly higher levels of total homocysteine were found in pituitary adenoma and glioblastoma multiforme compared with other types of tumors. Methionine and cysteine concentrations did not differ significantly according to diagnosis. CONCLUSIONS: This is the first work concerning the concentrations of aminothiols in brain tissues. The results obtained indicate the metabolic pathways that are involved in tumor formation and/or its progress, including the toxic effects of homocysteine.

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.

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.

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.

Levels of testosterone, allopregnanolone and homocysteine in severe hypothyroidism.

Hypothyroidism is very often associated with cardiovascular diseases and neurological complications. Recently, homocysteine has been studied as an independent risk factor for atherosclerosis which negatively affects vascular endothelial cells. Because homocysteine metabolism is related to thyroid and steroid hormones, we studied these relationships in severe hypothyroidism and in euthyroid state. Homocysteine, testosterone and allopregnanolone concentrations were measured in the fasting plasma from 16 women who underwent total thyroidectomy, and who were either hypothyroid or euthyroid. Although all women used oral contraceptives, they were not protected against hyperhomocysteinemia during hypothyroid state. With the normalization of thyroid hormone concentrations homocysteine levels decreased to normal levels. There was a positive correlation between testosterone and homocysteine in the euthyroid state which suggests that not only estrogens but also androgen state should be considered in future studies on homocysteine.