Time course of urinary neopterin in a non-Hodgkin's lymphoma patient during chemotherapy and radiotherapy.

The objective of this study was to follow urinary neopterin in a patient affected by non-Hodgkin's lymphoma during the three months treatment from the onset of the disease. In the study a patient affected by non-Hodgkin's lymphoma in Stage IV (centrocyto-centroblastic type) was enrolled. He was treated with combined chemotherapy and local radiotherapy. Neopterin was measured by high performance liquid chromatography in the first morning urine specimens. The time course of urinary neopterin levels ranged from 110 to 524 micromol x mol(-1) creatinine (mean 261, SD 67.5 micromol x mol(-1) creatinine). Over 70 % of the received values were higher than the upper limit of normal excretion of healthy subjects. Longitudinal analysis showed a relatively big variance of urinary neopterin with a tendency of decrease during the treatment. The significant decrease of urinary neopterin was observed till after the radiotherapy period which followed the chemotherapy period. In conclusions, the response to the therapy was accompanied by a reversal tendency of neopterin excretion to physiological values. This study confirms neopterin as a suitable additional parameter for the control of non-Hodgkin's lymphoma therapy.

Homocysteine during the menstrual cycle in depressive women.

BACKGROUND: Two possible factors that may have a causal relation with both depressive disorder and cardiovascular disease are elevated homocysteine and steroid hormones. Our previous study found significant changes in the plasma homocysteine concentration during the menstrual cycle in healthy women. The purpose of this study therefore was to test homocysteine in depressive women treated with fluoxetine during the menstrual cycle. MATERIALS AND METHODS: Thirteen premenopausal women suffering from mixed anxiety-depressive disorder and a control group of 15 healthy women were enrolled in this study. The homocysteine concentration was determined by high-performance liquid chromatography with fluorescence detection, and estradiol, progesterone and cortisol by RIA methods. RESULTS: We found significantly higher plasma homocysteine concentrations in the follicular phase than in the luteal phase of the menstrual cycle in both the depressive group (P < 0.003) and the controls (P < 0.0009). Moreover, the patient values of total homocysteine were significantly higher in the follicular phase (P < 0.03) and also in the luteal phase (P < 0.007) than the values of the controls. Estradiol and cortisol were significantly higher in the follicular phase of the patients compared with the control group. CONCLUSION: According to our results, women suffering from mixed anxiety-depressive disorder have not only significantly different concentrations of homocysteine in the follicular and luteal phase of the menstrual cycle but also higher plasma homocysteine compared with healthy women. More elevated homocysteine in the depressive than in the healthy premenopausal women points to the notion that psychological factors might be important when considering the homocysteine concentration.

Homocysteine and steroids levels in metformin treated women with polycystic ovary syndrome.

UNLABELLED: Risk for atherosclerosis is increased in women with polycystic ovary syndrome (PCOS). Homocysteine (Hcy) is one of the independent risk factors for ischemic heart disease. We examined the effect of metformin (M) treatment on Hcy levels, steroids and glycide tolerance in PCOS. MATERIAL AND METHODS: 9 women with PCOS (defined as hyperandrogenemia and chronic anovulation); age 20 +/- 3.8 yrs, BMI 28.1 +/- 6.5 kg/m(2); examined in the follicular phase of spontaneous menstrual cycle before and after 27 +/- 4 weeks of treatment with M 1000 mg/day. The plasma concentrations of Hcy, DHEA, DHEA-S, cortisol (F), allopregnanolone (HPO), 17OHpregnenolone (17OHPl), insulin (I) and blood glucose (G) before and after the course of M were measured. RESULTS: After the course of M, Hcy significantly increased (10.1 +/- 2.6 to 13.4 +/- 5.1 micromol/l, p < 0.05.). There was no significant change in levels of I, HPO, F, DHEA-S and 17OHPl. DHEA levels increased significantly (from 26.9 +/- 15.7 to 44.4 +/- 24.6 nmol/l, p < 0.05). A borderline significant trend towards reduction in waist-hip ratio was seen (from 0.986 +/- 0.042 to 0.951 +/- 0.085; p < 0.06). CONCLUSIONS: Treatment with metformin in women with PCOS can lead to the increase in homocysteine levels--a risk factor for atherosclerosis.

Effect of treatment of hypothyroidism on the plasma concentrations of neuroactive steroids and homocysteine.

Autoimmune thyroiditis with hypothyroidism is frequently accompanied by symptoms of psychiatric disorders and atherogenic changes in lipid metabolism. Recent studies suggest that some neuroactive steroids and homocysteine are involved in the pathophysiology of both disorders. Homocysteine metabolism may be affected by some steroids. We were interested if the treatment of hypothyroidism would affect the above factors. We studied plasma concentrations of allopregnanolone, pregnenolone sulfate, dehydroepiandosterone and its sulfate, progesterone, estradiol and homocysteine in 14 patients (12 women, 2 men) during the 3-month treatment with levothyroxine. Steroids and thyroid function were monitored by measuring thyrotropin, free triiodothyronine, free thyroxine and levels of thyroid antimicrosomal antibodies and antibodies to thyroglobulin. We have found that with the restoration of the thyrotropin level, free triiodothyronine, free thyroxine and homocysteine levels decreased, but the levels of steroids were not significantly altered. Steroid concentrations correlated negatively with the level of thyroid antimicrosomal antibodies.

Homocysteine in breast cyst fluid.

BACKGROUND: Elevated plasma homocysteine concentrations have been reported in a variety of carcinoma, including those of the breast. The risk of breast cancer is higher in patients suffering from gross cystic disease. The breast cyst fluid contains unusual amounts of low- and high- molecular substances, including steroid hormones and their conjugates. The present study was undertaken to find out the presence of homocysteine in the fluid filling the cysts and have its concentration compared with other thiols, levels of Na+/K+ ratio and steroid hormones. Materials and methods Fourteen women suffering from gross cystic disease were enrolled in this study. Cystic concentrations of homocysteine (Hcy), cysteine (Cys), cysteinylglycine (Cys-Gly) and glutathione (GSH) were determined by high performance liquid chromatography, with fluorescence detection; estradiol (E2), progesterone, allopregnanolone and pregnenolone sulfate (PregS) by RIA methods. RESULTS: Mean levels of Hcy, Cys, Cys-Gly, Na+/K+, E2 and PregS in the fluid filling the breast cysts were significantly higher than the corresponding plasma concentrations. In addition, a negative correlation was found between cystic Hcy and the Na+/K+ ratio (Rs = -0.72, P = 0.003) and positive correlations between cyst Hcy and estradiol (Rs = 0.64, P = 0.018) and Hcy and PregS (Rs = 0.60, P = 0.025). Conclusion The study provides the first evidence of thiol concentrations in the breast cyst fluid. The finding of a negative correlation between homocysteine and the Na+/K+ ratio support the idea that the homocysteine concentration in breast cysts might be used clinically as a marker for the development of breast cancer disease.

Allopregnanolone, pregnenolone sulfate, and epitestosterone in breast cyst fluid.

The risk of breast cancer is 2 to 5 times higher in patients suffering from gross cystic disease. Breast cysts are categorized into two groups (type I and type II) according to the concentration of electrolytes in the cyst fluid. The two types also differ with respect to accumulation of steroids and steroidogenic enzyme activity. In type I cysts a higher risk of breast carcinoma could be expected. Here, we studied a possible relationship between the type of cyst and levels of epitestosterone (an endogenous antiandrogen), allopregnanolone (a product of 5alpha-reductase activity), and pregnenolone-sulfate (an activator of N-methyl-D-asparate receptors). We have found five times higher levels of epitestosterone in BCF in comparison with the circulation. Allopregnanolone levels were similar to those in plasma of women in the luteal phase of the menstrual cycle. Pregnenolone-sulfate levels in BCF were about two orders of magnitude higher when compared with the circulation. No differences were found in concentrations of the steroids studied between the types of cysts.

Changes of plasma total homocysteine levels during the menstrual cycle.

BACKGROUND: It is known that plasma total homocysteine (tHcy) levels are lower in premenopausal and pregnant women compared with postmenopausal women. To confirm the suggestion that sex steroid hormones are nongenetic factors affecting homocysteine metabolism, we investigated the effect of natural steroid hormone levels on the fasting plasma tHcy in healthy women during the menstrual cycle. MATERIALS AND METHODS: Fifteen premenopausal women were enrolled in this study. Plasma tHcy, estradiol, progesterone and cortisol concentrations were measured in the luteal and follicular phase. The plasma tHcy concentration was determined by high performance liquid chromatography with fluorescence detection, and the steroid hormones by RIA methods. RESULTS: Mean homocysteine values increased from 7.8 micromol L-1 in the luteal phase to 8.9 micromol L-1 in the follicular phase (P < 0.000005, Student's paired t-test). We also found slight negative but insignificant correlations of homocysteine levels with estradiol in both phases of the menstrual cycle. In the case of cortisol and progesterone, no significant correlations with plasma homocysteine were found. CONCLUSION: The study provides the first evidence of significant differences in plasma homocysteine concentration during the menstrual cycle. From our observed findings it is necessary to account for the phase of the menstrual cycle when determining homocysteine in premenopausal women.

Effect of 4-cholesten-3-one on steroidogenesis and morphology of rat adrenal cortex.

The production of corticosteroids from endogenous precursors was decreased in adrenal glands of male rats fed a diet containing one per cent of 4-cholesten-3-one for 3 and 7 days. In contrast, the conversion of labelled progesterone into corticosteroids was only slightly affected as shown by the increased aldosterone to 18-hydroxydeoxycorticosterone ratio. Morphological method revealed lipoid adrenal hyperplasia developing progressively during the observation period. In the adrenal gland, the content of 4-cholesten-3-one rose slightly and, as shown in the experiment with labelled 4-cholesten-3-one, it can serve only as a weakly effective precursor of corticosteroid biosynthesis. Cholesterol content in the adrenals decreased and lipoid hyperplasia could not be explained therefore by cholesterol accumulation.