Brain-derived neurotrophic factor and ciliary neurotrophic factor in maternal plasma and umbilical cord blood from pre-eclamptic and physiological pregnancies.

The aim of the study was to investigate the circulating levels of ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in maternal serum and umbilical cord blood from respective pregnancies in pre-eclampsia (PE) cases and a control cohort. A total of 12 pre-eclampsia cases and 34 healthy controls were enrolled and the maternal peripheral blood - umbilical cord blood duos, were examined for BDNF and CNTF levels. BNDF levels were significantly higher in umbilical cord blood from pre-eclamptic pregnancies; there was also significant difference between maternal plasma and umbilical cord blood levels of BDNF (p < 0.001) in the controls. The CNTF levels in umbilical cord blood (CNTF-UCB) were significantly higher in PE cases than in the controls (p = 0.03). Significant differences were observed in expression of BDNF and CNTF proteins in maternal peripheral blood and umbilical cord blood between pre-eclampsia cases and healthy controls.

Visfatin is secreted into the breast milk and is correlated with weight changes of the infant after the birth.

INTRODUCTION: Visfatin is a recently identified adipokine with numerous metabolic and immunoregulatory properties that has been implicated in the regulation of the white adipose tissue (WAT) and significant changes in visfatin levels were reported during pregnancy. The aim of the study was to investigate dynamics of visfatin levels in maternal serum and human breast milk during a 180-d period after the delivery. MATERIALS AND METHODS: : Breast milk and venous blood samples were obtained from 24 healthy lactating women with uncomplicated, physiological pregnancy and appropriate-for-gestational age neonates and serum-milk sample duos were collected at the time of birth, at the 1-3, 12-14, 28-30, 88-90 and 178-180 postpartum. RESULTS: Our study demonstrates that (1) visfatin is abundantly secreted into breast milk in humans, reaching approx. 100× higher concentrations compared to maternal serum; (2) visfatin concentrations in maternal serum show significant variations after the delivery and (3) visfatin concentration in colostrum could be used for prediction of the subsequent weight development (less/more severe weight loss during first 3 days after the birth) of the infant. DISCUSSION: Our data suggest that visfatin could play an important role in regulation of adiposity of the infant after the birth.

Circulating levels of B-cell activating factor in paediatric patients with malignancy with or without cancer-related cachexia.

BACKGROUND: Cancer-related cachexia is a multifactorial syndrome characterised by progressive loss of body weight and it affects a large proportion of patients with advanced cancer. Cachexia is associated with reduced treatment tolerance, response to therapy, quality of life and duration of survival, whereas some of its mechanisms are shared across the whole continuum of diseases in the population, either cancer-related or non-cancer related e.g. systemic inflammation, increased lipolysis, insulin resistance and reduced physical performance. However, so far there has been only little effort to utilise the integrative physiology of adipose tissue to achieve therapeutic gain. B cell-activating factor (BAFF) is a novel member of the TNF ligand superfamily, is mainly produced by myeloid cells and has recently been shown to participate in B-cell survival and B- and T-cell maturation, but also in adipogenesis. Therefore, it represents an elegant candidate molecule linking the immune system and adipose tissue metabolism, both being involved deeply in the pathogenesis of cachexia. Moreover, it has been described very recently that BAFF directly influences secretion of IL-6 and IL-10. MATERIAL AND METHODS: In this study, pre-treatment circulating levels of BAFF were investigated in a cohort of 83 paediatric patients with malignancy (0-18 y) with or without cancer-related cachexia using ELISA-based methodology. RESULTS: Apart from logical significant associations of BAFF circulating levels with disease severity in B-lineage malignancies (ALL or B-cell lymphomas), we observed significant elevation of BAFF in adolescent patients with Ewing sarcoma and rhabdomyosarcoma, compared to the circulating levels appropriate for given age. CONCLUSION: To the best of our knowledge, this is so far the first study focusing on BAFF in paediatric malignancies with or without cancer-related cachexia. More research into whether BAFF can represent a useful circulating biomarker for detection and monitoring of the cancer-related cachexia is imperative.

[Chronic pancreatitis and the skeleton]. / Chronická pankreatitida a skelet.

The aim of our work was to determine the incidence of bone demineralization in patients with chronic pancreatitis, following the relation between the funcionality of the pancreatic tissue and etiological factors in the development of osteopathy and calciophosphate metabolism. Prospectivelly, during 1 year we followed 55 patients with chronic pancreatitis of different etiology verified by endoultrasound. Patients with other possible cause of osteopathy were not included in the group. In the following of calciophosphate metabolism we determined different biochemical parameters and we measured the bone mass with densitometry in standard locations. In the patients that we followed we managed to show high proportion (43.7%) of bone demineralization, however, no relation between the bone demineralization and the grade of chronic pancreatitis or the operation of pancreas was proved. Vitamin D deficiency has a significantly negative impact on bone metabolism, which is potentiated by pancreatic insufficiency and long-time alcohol abuse.

[Is there circadian variation of big endothelin and NT-proBNP in patients with severe congestive heart failure?]. / Existuje diurnální variabilita big endotelinu a NT-proBNP u nemorných s tezkým chronickým srdecním selháním?

INTRODUCTION: Circadian rhytmus have long been recognized to occur in many biologic phenomena, including secretion of hormones as well as autonomic nervous system. There is increasing evidence that circadian rhythms have been also found in cardiovascular events, for example, myocardial infarction, sudden cardiac death as well as stroke have shown a circadian pattern of the distribution. The pathophysiology and the mechanism underlying these variations are the focus of much investigation, while i tis not full understood up to date. Heart rate, blood pressure, neurohumoral vasoactive factors, such as plasma norepinephrine levels and renin activity, and probably also contractility are increased in the morning hours. THE AIM OF OUR STUDY: To evaluate the circadian variability of plasma big endothelin and NT-proBNP level in patients with severe heart failure. PATIENTS: 13 patients with severe heart failure, stable for at least one month, male/female--8/5, NYHA III/IV--11/2, mean left ventricle ejection fraction 23 +/- 5%, mean cardiothoracic ratio 59 +/- 7%, all treated with RAAS blocade (11 x ACE-I, 2x ARB), all treated with diuretics, 12 patients treated with beta-blockers, 7 with digoxin. The cause of heart failure was ischemic heart disease (9) or dilated cardiomyopathy (4). METHODS: Blood samples for big endothelin and NT-proBNP were taken every two hours during a standartised daily regime. RESULTS: Mean plasma level of big endothelin (ranging from 1.25 to 1.71 pmol/l) had significant diurnal variability (upper limit of normal values 0.7 pmol/l). Mean plasma level of NT-proBNP (ranging from 782 to 934 pmol/l) had no diurnal variability (upper limit of normal values of 350 pmo/l). SUMMARY: Plasma level of NT-proBNP is stable during 24 hours and shows no circadian variability. Plasma big endothelin showed a morning peak after a systematic increase during bed rest. NT-proBNP could be evaluated any time during the day, big endothelin sample should be taken during standartised condition.

Occurrence of metabolic osteopathy in patients with chronic pancreatitis.

INTRODUCTION: Chronic pancreatitis is an inflammatory disease manifested by maldigestion and, in an advanced stage, by malabsorption. The aim of our research was to monitor the occurrence of metabolic osteopathies (osteopenia, osteoporosis and osteomalacia) in patients with chronic pancreatitis. PATIENTS AND METHODS: The group consisted of 73 patients (17 women and 56 men) in different stages of chronic pancreatitis. In all patients we determined serum concentrations of Ca, P, 25-OH vitamin D, 1,25-(OH)(2) vitamin D, alkaline phosphatase and its bone isoenzyme. Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA) in the lumbar spine (L(1)-L(4)) and in the proximal femur. When bone pathology was identified by DXA, we determined the other to exclude other causes of secondary osteopathy and the 24-hour loss of calcium and phosphorus in the urine. RESULTS: Osteopathy was found in 39% of patients, i.e. osteopenia in 26%, osteoporosis in 5% and osteomalacia in 8% of cases. CONCLUSION: The occurrence of relatively high percentages of metabolic osteopathies in patients with chronic pancreatitis may correlate, namely in advanced stages of the disease, with the malabsorption of vitamin D to the enterohepatic circulation. In initial forms of pancreatitis, it is not possible to exclude progression of osteopathy due to changes of the intestinal flora, with disturbance of vitamin D absorption to the intestinal mucosa.

Genetics of humoral and cytokine activation in heart failure and its importance for risk stratification of patients.

The study objective is to prove an association among plasma concentration of big endothelin and endothelin-1, other clinical parameters and two frequent polymorphisms - G8002A and -3A/-4A - in the endothelin-1 (EDN-1) coding gene (6p21-23), and among plasma concentration of TNF alpha and gene polymorphisms TNF alpha -308 A/G, -238 A/G, TNF beta Ncol and 3'TACE (tumour necrosis factor alpha converting enzyme) in patients with chronic heart failure (CHF). The second objective is to find an association between polymorphisms G8002A and -3A/4A EDN-1 with diabetes mellitus (DM), peripheral artery disease (PAD) and myocardial infarction (MI) in patients with chronic heart failure (CHF). The study population included 266 patients with symptomatic CHF and proven dysfunction of the left ventricle (LV). Genotyping and plasma concentrations of humoral substances were examined in 224 patients with ejection fraction (EF) below 40%. No associations between plasma concentrations of endothelin-1 and big endothelin and polymorphisms G8002A (p=0.87, p=0.81) and -3A/-4A (p=0.871, p=0.749) in the gene coding endothelin-1 were found. No associations were observed between plasma concentration of TNF alpha and genotypes in four polymorphisms in TNF alpha, beta and TACE genes. A significant correlation was seen between plasma concentration of big endothelin and pulmonary congestion. Patients with ischemic heart disease (IHD) and previous MI showed a difference in the distribution of genotype G8002A for endothelin-1: allele G 0.718 and A 0.282 vs those without MI: allele G 0.882 and A 0.118, (p<0.05). Patients with IHD and DM had allele G in 0.67 and A 0.33, while those without DM had allele G in 0.790 and A in 0.209 (p<0.03). Patients with IHD and concomitant PAD had allele G in 0.718 and A in 0.282 vs those without PAD allele G in 0.882 and A in 0.118 (p<0.0004). Patients with dilative cardiomyopathy (DCMP) showed no differences in genotype G8002A and presence of DM or PAD. It might be speculated that in the case of endothelin-1 and TNF alpha in CHF the genetic determination is not important, and plasma concentrations are influenced more by the disease severity. Ischemics with previous MI, concomitant DM or PAD showed more frequently allele A and less often allele G than those without these diseases. A genotype with allele A is associated with higher risk of concomitant diseases.

Effect of methamphetamine on cytochrome P450 activity.

Amphetamine-based drugs, including methamphetamine, are some of the most widely used illegal drugs in the world. Methamphetamine is metabolized by the cytochrome P450s, the latter also being involved in the metabolism of many drugs and other xenobiotics. The effect of methamphetamine pretreatment (10 mg kg-1, intraperitoneally once daily for 6 days) on the activity of the P450 enzymes was assessed both in the rat isolated perfused liver and in vivo. The rate of 4-hydroxydiclofenac production was significantly enhanced in vivo, indicating a possible stimulatory effect on P4502C6. Similarly, the kinetics of tolbutamide and dextromethorphan in isolated perfused rat liver indicate a significant increase in both P4502C6 and the P4502D subfamily. No significant changes in midazolam kinetic in the isolated perfused rat liver were observed. The potential for methamphetamine to cause drug interactions is of clinical relevance and, therefore, it warrants further investigation. Until further drug interaction experiments are accomplished, the co-administration of drugs with methamphetamine should be conducted with caution.

Increased activity of superoxide dismutase in advanced stages of head and neck squamous cell carcinoma with locoregional metastases.

The aim of the study was to investigate relationship between activity of superoxide dismutase (SOD), malondialdehyde (MDA) and tumor necrosis factor alpha (TNFalpha) and between Ala-9Val polymorphism in the gene encoding MnSOD (SOD2) and the initial stage and prognosis of the head and neck squamous cell carcinoma (HNSCC). Prospective study cohort comprised 88 patients who underwent surgical treatment for the diagnosis of HNSCC (53 patients were diagnosed with locoregional metastatic spread (N+) at the time of diagnosis). After the initial surgery subjects were followed for the subsequent period of 26 months during which 14 manifested relapse. Genotypes were detected by the PCR-based methodology. Activity of p-SOD, ery-SOD and TNFalpha were determined by ELISA, and the concentration of MDA by high performance liquid chromatography. Genotype and allele frequencies of the Ala-9Val differed neither between groups defined according to the stage of primary disease (TNM), nor between relapse vs. remission groups after the follow-up (p>0.05). Activity of p-SOD was significantly higher in T3/4 stage compared to T1/2 (p=0.01) and was also higher in N+ compared to N0 patients (p=0.002). Carriers of the Ala/Ala genotype had higher p-SOD activity (p=0.04). There was no significant difference in DFI between SOD2 genotype groups (p>0.05), however, the Ala/Ala group exhibited the shortest median DFI. In conclusion, our results suggest that increased p-SOD at the time of the initial treatment for HNSCC is connected with greater extent and nodal metastatic spread of the initial disease and with an earlier relapse of the disease. Progression of the disease might be further modified by the presence of Ala/Ala genotype of the SOD2. Activity of p-SOD could thus offer diagnostic as well as prognostic value.

Neurohumoral activity, heart failure and prognosis in patients with end-stage renal disease treated by hemodialysis.

BACKGROUND: Chronic renal failure treated by regular hemodialysis is frequently accompanied by chronic heart failure; the mortality of both is high. AIM: To evaluate the role of markers of neurohumoral activation for the prognosis of patients treated with regular dialysis. PATIENTS: 99 patients with end-stage renal disease were followed up for 3 years. METHODS: Clinical evaluation, echocardiography, biochemistry including NT-proBNP and big endothelin (Big-ET). RESULTS: The incidence of heart failure was 97% and the 3-year mortality was 50%. The sensitivity of NT-proBNP and Big-ET level for the prediction of death was 0.712 and 0.824, respectively, and specificity 0.642 and 0.695, respectively. The cut-off points were NT-proBNP > or = 2,000 pg/ml and Big-ET > or = 1.55 pmol/l. Neither NT-proBNP nor Big-ET could be incorporated in the multivariate model for overall survival, which means that although both parameters significantly influenced overall survival as single risk factors, they were not effective in competition with the other significant predictors. CONCLUSION: Overall survival seems to be influenced namely by age, hemoglobin, left atrium diameter or pulmonary congestion class on chest X-ray, while probability of early risk was associated with Big-ET, history of diabetes mellitus, C-reactive protein, uric acid and hemoglobin. The only intersection of the models is hemoglobin as a thoroughly significant predictor.

[The importance of determination of Nt-proBNP and big endothelin in diagnosing chronic heart failure in patients on regular haemodialysis treatment]. / Význam stanovení Nt-proBNP a big endotelinu pro diagnostiku chronického srdecního selhání u nemorných v pravidelném hemodialyzacním programu.

We have followed 99 patients with end stage renal failure, treated by regular haemodialysis. Chronic renal failure is frequently accompanied by chronic heart failure (over 50%), especially by heart failure with preserved ejection fraction. Patients treated by regular haemodialysis had a tendency to cardiomegaly (51%), mild systolic dysfunction of the left ventricle (mean LVEF 53%) and diastolic dysfunction (88%) of the hypertrophic left ventricle. They had also activated endothelin and neurohumoral system. Only 3% of the patients had normal values of Nt-proBNP and big endothelin. The plasma level of Nt-proBNP in haemodialysed patients correlated with cardiothoracic ratio and with ejection fraction. The plasma level of big endothelin correlated only with cardiothoracic ratio.

[Variability of plasmatic levels of big endothelin and NT-proBNP in patients with heart failure in a chronic haemodialysis programme]. / Variabilita plazmatických hladin big endotelinu a NT-proBNP u nemocných se srdecním selháním v chronickém hemodialyzacním programu.

Inter-dialysis variability in levels of big endothelin and NT-proBNP in plasma were studied in 22 patients with established systolic and/or diastolic dysfunction of the left cardiac ventricle assigned to a chronic haemodialysis programme. The plasmatic level of NT-proBNP in all patients was practically unchanged. There was a falling trended between haemodialysis treatments but this was not statistically significant and in absolute values clinically insignificant. Fluctuations were found between individuals but on average all values were stable and high in the pathological range. No significant changes in the plasmatic level of big endothelin were found either. The average levels were again stable and insignificant and the indicated trend did not achieve clinical or statistical significance. The values were once again high in the pathological range. Plasmatic levels of NT-proBNP and big endothelin do not vary according to the phase of the dialysis cycle and mainly reflect the long-term condition of endothelium failure and long-term stress in the left ventricle. Concentrations are not affected by changes in volume or uraemia between dialysis treatments and the suggested trend towards a fall in NT-proBNP and a rise in big endothelin does not have a clear explanation. In any case, this trend remained within the pathological range and is probably not clinically significant.

Effect of methamphetamine on the pharmacokinetics of dextromethorphan and midazolam in rats.

Methamphetamine is the fourth most frequently reported compound associated with drug abuse on admission of patients to treatment centres after cocaine, heroin and marijuana. It is metabolized in the organism with a reaction that is catalyzed by cytochrome P450, mainly by the CYP2D and CYP3A subfamily, 4-hydroxyamphetamine and amphetamine being dominant metabolites. The present pharmacokinetic study was undertaken to investigate the possible influence of methamphetamine (10 mg/kg, i.p., once daily for six days) on the pharmacokinetics of dextromethorphane as a model substrate for rat cytochrome P-4502D2 and midazolam as a model substrate for CYP3A1/2. Animals received a single injection of dextromethorphane (10 mg/kg) or midazolam (5 mg/kg) in the tail vein 24 h after the last dose of methamphetamine or administration of placebo. The results of pharmacokinetic analysis showed a significantly increased rate of dextrorphane and 3-hydroxymorphinan formation, and a marked stimulatory effect of methamphetamine on CYP2D2 metabolic activity. Similarly, the kinetics of midazolam's metabolic conversion to hydroxy derivates of midazolam indicated a significant increase in CYP3A1/2 activity. The results showed that the administration of methamphetamine significantly stimulated the metabolic activity of CYP2D2 as well as that of CYP3A1/2. With regard to the high level of homology between human and rat CYP isoforms studied, the results may have a clinical impact on future pharmacotherapy for methamphetamine abuse.

Effect of St John's wort (Hypericum perforatum) on cytochrome P-450 activity in perfused rat liver.

St. John's wort (Hypericum perforatum) is a popular over-the-counter dietary supplement and a herbal antidepressant that has been implicated in drug interactions with substrates of several cytochrome P-450 (CYP) isozymes. The effects of the St. John's wort extract (100 mg/kg, i.p., once daily for 10 days) on metabolic activity of CYP450 were assessed in the system of isolated perfused rat liver. The substrates used in this study were tolbutamide (CYP2C6), dextromethorphan (CYP2D2) and midazolam (CYP3A2). Validated HPLC method was used to quantify all compounds of interest. St. John's wort administration affected CYP activity, causing a significant decline in AUC of dextromethorphan [F(4,31)=1511, p<0.001; PLSD, p<0.001] and AUC of midazolam [F(3,25)=221, p<0.001; PLSD, p=0.035] and a significant increase in AUC of tolbutamide [F(3,26)=200, p<0.001; PLSD, p<0.001]. St. John's wort administration resulted in a significant induction of CYP2D2 and CYP3A2, and in a significant inhibition of CYP2C6 metabolic activities.

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.

Big endothelin in chronic heart failure: marker of disease severity or genetic determination?

The first objective of the study was to compare the levels of big endothelin and endothelin-1 and other noninvasive parameters used for evaluation of disease severity in patients with stable chronic heart failure (CHF). Endothelin-1 and big endothelin plasma concentrations were measured in 124 chronic heart failure patients. The second objective of the study was to prove an association between endothelin-1 and big endothelin plasma levels and two frequent polymorphisms in the endothelin-1 coding gene (6p21-23) -3A/-4A and G (8002) A in patients with chronic heart failure. Thirdly, we tried to associate other noninvasive parameters of CHF, especially cardiothoracic index (CTI), NYHA classification, signs of pulmonary congestion (PC) and ejection fraction (EF) with determined genotypes of the two ET-1 polymorphic variants. There were significant differences between big endothelin levels in NYHA II versus IV (P<0.001) and NYHA III versus IV (P<0.001) and endothelin-1 in NYHA II versus IV (P<0.001) and NYHA III versus IV (P<0.001). No associations between plasma levels of endothelin-1 and big endothelin and polymorphisms G (8002) A and -3A/-4A in gene coding endothelin-1 were found. In patients with CHF with CTI above 60% the number of carriers of genotypes with ET-1 8002A (AA and AG genotypes) increases. Concerning on the -3A/-4A ET-1 polymorphism, we observed a significant difference in genotype distribution as well as in allelic frequency in the group of patients with CTI above 60% between patients without and with pulmonary congestion. The allelic frequency of 3A allele is twice elevated in the patients with pulmonary congestion (37.8 vs. 78.1%, respectively).

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.

[Big endothelin and chronic heart failure]. / Big endotelin a chronické srdecní selhání.

In a group of 124 patients the authors investigated the importance of assessment of plasma levels of big endothelin and endothelin 1 in patients with chronic heart failure as compared with other currently used non-invasive parameters. A six fold increase of plasma levels of both substances was found in patients in functional class NYHA IV as compared with patients in class NYHA II-III. But even patients in the milder stage of NYHA had twice as high values as compared with the standard of the healthy population. Similarly patients with interstitial pulmonary oedema had a twice as high level of both parameters as compared with patients who had a normal finding on X-ray or merely a redistribution of the pulmonary vascularization. The sensitivity of assessment of plasma levels is such that this examination could become part of the basic diagnosis.

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.