Urine selenium changes during pregnancy do not correlate with thyroid autoantibodies in a mildly iodine deficient population.

Selenium (Se) is a key component of iodinases; higher Se levels are associated with lower titers of antithyroid peroxidase antibodies (anti-TPO). Pregnancy exerts profound effects on thyroid function and autoimmunity. To assess the relationship of urine Se levels with thyroid function and autoimmunity in pregnant women residing in Athens, Greece, we studied prospectively 47 euthyroid women in uncomplicated singleton pregnancies (mean age + SD: 30 + 5 years) in each trimester, measuring urine Se levels, urine iodine, plasma thyrotropin (TSH), free thyroxine and triiodothyronine (FT4 and FT3), as well as levels of anti-TPO antibodies. Changes of the measured parameters were assessed over each trimester; thyroid parameters were assessed with relation to Se levels. Urine Se dropped by the third trimester, whereas urine iodine did not change appreciably during pregnancy. TSH and anti-TPO did not show appreciable changes; FT4 and FT3 gradually decreased as the pregnancy advanced. No relationship between urine Se levels and anti-TPO was found. During pregnancy, changes in urine Se levels accompany mild changes in thyroid function. However, we did not find some association between these changes and thyroid autoimmune activity over this period, probably because the effect of Se on thyroid autoimmunity may only become apparent in case of excess Se fortification.

Do lunar phases influence menstruation? A year-long retrospective study.

We assessed with cross-approximate entropy menstruation onset versus moon phases in 74 women with 980 menstrual cycles over a calendar year. In defiance of traditional beliefs and contrary to what some researchers have argued with short-term research work, in this long-term study we did not find any synchrony of lunar phases with the menstrual cycle.

An empiric treatment for idiopathic oligozoospermia revisited: a 20-year investigative saga.

A series of studies aiming at introducing an effective treatment for idiopathic oligozoospermia was conducted in a step-wise fashion spanning over a 20-year period. The concept was that co-administration of an accessory gland-stimulating androgen, testosterone undecanoate (40 mg t.i.d.) and the FSH raising anti-oestrogen tamoxifen citrate (10 mg b.i.d.) may improve sperm parameters. A prerequisite for such an effect was the demonstration that testosterone undecanoate had no suppressing action on pituitary-testicular axis. In this context, initial studies demonstrated no change in basal or stimulated gonadotrophin and testosterone secretion in short- or long-term protocols. Two subsequent trials with this combination showed a marked improvement of sperm parameters and pregnancy incidence, with a seasonal variation noted in response to treatment, this being higher during the cold seasons of autumn and winter. Regarding the mechanism of testosterone undecanoate's action, a recent study from our unit showed that its administration resulted in a marked rise of serum DHT levels. Because this steroid is an epididymal function promoter, it appears that its contribution in the combination is mediated mainly through its DHT raising effect. By and large, this empiric approach for the treatment of idiopathic oligozoospermia was satisfactorily documented after a 20-year investigative saga.

'Value of FSH and inhibin-B measurements in the diagnosis of azoospermia'--a clinician's overview.

Azoospermia can be either of obstructive ctiology or due to the testis' failure to initiate or maintain spermatogenesis. FSH acts through its receptor at Sertoli cell level and modulates spermatogenesis initiation and maintenance. Inhibin B is a Sertoli cell product expressing the functional capacity of the cell and in an indirect way the state of seminiferous tubule activity. Both FSH and inhibin B differentiate clearly testicular from extra-testicular pathology of azoospermia while, none of these hormones has been convincingly established as predictory index for the finding of spermatozoa in TESE.

Seasonality in sperm parameters in normal men and dyspermic patients on medical intervention.

This study attempted to investigate the presence of seasonal variations in sperm parameters and to evaluate the season's impact on the response to treatment in men with idiopathic oligozoospermia (IO). To this end, a retrospective analysis of the records of 294 men, who participated in a controlled study, was performed. This sample included IO men (n = 106) treated with tamoxifen citrate (10 mg b.i.d.) and testosterone undecanoate (40 mg t.i.d.) or placebo (n = 106) and normozoospermic men (n = 82) serving as controls. Outcome measures included sperm parameters, functional sperm fraction (FSF) and incidence of pregnancy. Analysis showed a raised frequency of high FSF values and increased area under the response curve (AURC) for FSF mean during autumn-winter seasons in patients on active treatment compared with those in placebo (P < 0.05-P < 0.04). Moreover, receiver operation characteristics (ROC) curves for a >100% FSF rise significantly discriminated autumn-winter from other seasons (P < 0.001, all), whereas active treatment showed higher than placebo FSF values particularly during autumn and winter (P < 0.001, all). The pregnancy incidence was higher in the autumn in all groups. It is concluded that FSF values showed a better response to active treatment during autumn and winter, indicating that commencement of empirical treatment at this time in IO men may stand a better chance to succeed.

Liver triacylglycerols and free fatty acids in streptozotocin-induced diabetic rats have atypical n-6 and n-3 pattern.

In diabetes there is a decrease in membrane arachidonic (AA) and docosahexaenoic (DHA) acids and a concomitant increase in linoleic (LA) and alpha-linolenic (ALA) acids. This metabolic perturbation is thought to be due to impaired activity of Delta(6)- and Delta(5)-desaturases. Triacylglycerols are the major lipid pool in plasma and liver tissue and have a significant influence on fatty acid composition of membrane and circulating phospholipids. Data on the distribution of n-6 and n-3 polyunsaturated fatty acids of triacylglycerols in diabetes are sparse. We investigated whether streptozotocin-induced diabetes in Sprague-Dawley rats alters fatty acid composition of triacylglycerols and free fatty acids of liver tissue. The animals were fed a breeding diet prior to mating, during pregnancy and lactation. On days 1-2 of pregnancy, diabetes was induced in 10 of the 25 rats. Liver was obtained at post partum day 16 for analysis. Relative levels of LA (P=0.03), dihomo-gamma-linolenic acid (DHGLA) (P=0.02), AA (P=0.049), total n-6 (P=0.02), ALA (P=0.013), eicosapentaenoic acid (EPA) (P=0.004), docosapentaenoic acid (22:5n-3, DPA) (P=0.013), DHA (P=0.033), n-3 metabolites (P=0.015) and total n-3 (P=0.011) were significantly higher in the triacylglycerols of the diabetics compared with the controls. Similarly, liver free fatty acids of the diabetics had higher levels of LA (P=0.0001), DHGLA (P=0.001), AA (P=0.001), n-6 metabolites (P=0.002), total n-6 (P=0.0001), ALA (P=0.003), EPA (P=0.015), docosapentaenoic (22:5n-3, P=0.003), DHA (P=0.002), n-3 metabolites (P=0.005) and total n-3 (P=0.001). We conclude that impaired activity of desaturases and/or long chain acyl-CoA synthetase could not explain the higher levels of AA, DHA and n-6 and n-3 metabolites in the diabetics. This seems to be consistent with an alteration in the regulatory mechanism, which directs incorporation of polyunsaturated fatty acids either into triacylglycerols or phospholipids.

Post-natal modulation of heart and liver phosphoglyceride fatty acids in pups.

BACKGROUND: Maternal dietary fats alter tissue fatty acids of the fetus and suckling pups. However, the possible change in tissue composition in response to the high oxygen tension extrauterine milieu independent of diet is not well understood. METHODS: We have compared the fatty acids of heart and liver choline (CPG) and ethanolamine (EPG) phosphoglycerides of rat offspring at birth and post-natal day 15. Sprague-Dawley rats were fed a breeding diet prior to mating, pregnancy and lactation. A proportion of each litter was sacrificed and the liver and heart were obtained for analysis. Changes in fatty acid composition specific to tissue (heart and liver) and phosphoglyceride (CPG and EPG) occurred post-natally. RESULTS: Relative levels of palmitate and oleate decreased and those of stearate increased in both the heart and liver phosphoglycerides of the suckling pups. There was a reduction in arachidonate/linoleate ratio primarily due to the increase in linoleic acid. With the exception in the heart EPG, the levels of arachidonic acid did not decrease concomitantly. Although the fatty acid composition of the diet did not change between pregnancy and lactation, docosahexaenoic and total n-3 increased in heart CPG and EPG and liver CPG of the suckling pups. Evidently, membrane fatty acid modulation, independent of maternal dietary fat, occurs in the extrauterine environment. It seems to favour the accretion of linoleic, arachidonic, docosahexaenoic and total n-3 fatty acids. CONCLUSION: Since there appears to be some parallel between the very preterm human neonate and rat pups with regard to nutrient store at birth and the neonatal developmental time window, our results may have relevance for the understanding of fatty acid metabolism and turnover in the human neonate.

Maternal diet high in fat reduces docosahexaenoic acid in liver lipids of newborn and sucking rat pups.

The effect of a maternal diet high in fat, similar to Western foods, and of diabetes on liver essential fatty acid composition of the mother and the newborn and sucking pups was investigated. Female Sprague-Dawley rats were fed on either a low-fat (42 g/kg) or a high-fat (329 g/kg) diet for 10 d before mating, throughout pregnancy and post-partum. On the first day of pregnancy, diabetes was induced by intravenous administration of streptozotocin in half the animals from the two diet groups. Half the pups were killed at birth, and the remaining pups and mothers at days 15 and 16 respectively. At birth, there was a significant reduction in the proportions of docosahexaenoic acid (DHA) in the liver phosphoglycerols and neutral lipids of the pups of both high-fat control and diabetic mothers compared with those of low-fat control and diabetic mothers. Diabetes decreased arachidonic (AA) and linoleic acid values in both the low- and high-fat groups at birth. The sucking pups of both the high-fat control and diabetic mothers exhibited a significant reduction in DHA and a concomitant compensatory increase in AA and a lowering in DHA-AA balance. In the mothers, the high-fat diet significantly increased the proportions of DHA in ethanolamine phosphoglycerols but had no observable effect in choline phosphoglycerols and neutral lipids. In the fetus the DHA level (g/100 g total fatty acids) was disproportionately reduced by the maternal high-fat diet. The adverse effect of the high-fat diet on the level of DHA (g/100 g total fatty acids) was greater in the neonate (and by implication the fetus) than in the sucking pups or mothers. It is concluded that a distortion of the biochemistry is induced in the offspring through a maternal high-fat diet, without genetic predisposition.

Offspring of normal and diabetic rats fed saturated fat in pregnancy demonstrate vascular dysfunction.

BACKGROUND: Disturbances of the in utero environment may "program" for disease in later life. In this study, we determined whether dietary fat supplementation and/or diabetes in pregnancy can adversely affect vascular function in the offspring. METHODS AND RESULTS: Female Sprague-Dawley rats were fed a breeding diet or a diet high in saturated fat (30% wt/wt) for 10 days before mating, throughout pregnancy, and postpartum. Endothelium-dependent relaxation to acetylcholine was blunted in isolated femoral arteries of 15-day-old weanling pups from dams fed the 30%-fat diet. Endothelial dysfunction and enhanced constrictor responses to norepinephrine were also observed in an additional study of 60-day-old offspring of dams fed 20% saturated fat. Rats with streptozotocin-induced diabetes were also fed saturated fat during pregnancy. Femoral arteries from their 15-day-old offspring showed impairment of endothelium-dependent dilation and enhanced constrictor responses to norepinephrine and the thromboxane mimetic U46619 compared with young offspring of high-fat-fed normal dams. The 30%-fat diet was also deleterious to vascular function in the maternal diabetic animals when assessed in mesenteric arteries 16 days postpartum. CONCLUSIONS: A high-fat diet in pregnancy led to vascular dysfunction in rat weanlings and young adult offspring. Vascular function further deteriorated in weanlings if the maternal rat was diabetic.

Measuring pre-hepatic insulin secretion using a population model of C-peptide kinetics: accuracy and required sampling schedule.

The accuracy of calculations of pre-hepatic insulin secretion were investigated, to provide independent validation of a population model of C-peptide kinetics. The effects of sampling frequency were also assessed. Five normal subjects (aged 28 to 43 years; BMI (kg/m2) 20.5 to 24.5) and five subjects with non-insulin-dependent diabetes mellitus (NIDDM) treated by diet alone (aged 34 to 57 years; BMI 22.6 to 25.6) were given a variable intravenous infusion of biosynthetic human C-peptide (BHCP) (t=-60 to 240 min) mimicking meal stimulated C-peptide secretion, with short-term oscillations (peak approximately every 12 min) superimposed on the infusion profile. Plasma C-peptide was measured every 5 min (t=0 to 240 min). The BHCP infusion was reconstructed from C-peptide measurements using a population model of C-peptide kinetics and a deconvolution method. Bias, defined as the percentage difference between the total amount of calculated BHCP and the total amount of infused BHCP (t=0 to 240 min), indicated that overall C-peptide secretion can be measured with 14% [95% confidence interval (CI) -11 to 39%] and 21% (95% CI -3 to 45%) accuracy in normal subjects and subjects with NIDDM respectively. Accuracy was not reduced by reducing the sampling frequency to every 30 min. The root mean square error, measuring the average deviation between the infused and normalised calculated BHCP profiles, was also independent of the sampling frequency [mean (95% CI) 0.9 (0.3 to 1.6) pmol/kg per min in normal subjects; 1.0 (0.9 to 1.1) pmol/kg per min in subjects with NIDDM]. Deconvolution employing a population model of C-peptide kinetics can be used to estimate postprandial total C-peptide secretion with biases of 14% and 22% respectively in normal subjects and subjects with NIDDM. Plasma C-peptide samples need only be drawn every 30 minutes.

The effect of maternal glycemic control on fetal growth in diabetic pregnancies.

In this prospective study, we examined the effect of maternal glycemic control on fetal growth in pregnancies complicated by pregestational diabetes. One hundred and sixty-five pregestational diabetic pregnancies were studied with serial ultrasound scans and fetal growth was examined as a function of maternal glycemic control. There was a significant, although small, reduction in fetal biparietal diameter growth rate in the presence of poor maternal glycemic control during the first half of the pregnancy. In the second half of pregnancy, maternal hyperglycemia contributed to fetal macrosomia. We conclude that in pregnancies with pregestational diabetes, maternal hyperglycemia affects fetal growth in a biphasic manner. As a result of that, although babies born to diabetic mothers appear of relatively overall normal size and weight, they may have smaller heads than their potential and more fat.

Serum lipid, lipoprotein and apolipoprotein changes in gestational diabetes mellitus: a cross-sectional and prospective study.

AIMS: To compare serum lipid, lipoprotein and apolipoprotein concentrations during and six to 12 months after pregnancy in control and diabetic women. METHODS: The serum lipid, lipoprotein and apolipoprotein concentrations were measured in 20 women with gestational diabetes mellitus (GDM) and 22 women with normal glucose tolerance (controls) during the third trimester of pregnancy and six to 12 months after delivery. RESULTS: During pregnancy the women with GDM had higher serum triglyceride (mean (95% confidence interval (CI)), 2.91 (2.22-3.51) v 2.1 (1.75-2.52)) but lower low density lipoprotein (LDL) cholesterol concentrations compared with controls (mean (SD), 3.08 (1.2) v 4.01 (1.1). Total cholesterol, high density lipoprotein (HDL) cholesterol and apolipoprotein concentrations were not significantly different between the two groups. After pregnancy, total cholesterol, HDL cholesterol, triglyceride, and apolipoprotein A1 and B decreased in a parallel manner, resulting in lower concentrations, comparable between the two groups. LDL cholesterol concentrations decreased after pregnancy in the controls (mean (SD), 4.01 (1.1) v 2.69 (0.6)) but not in those with GDM (3.08 (1.2) v 2.72 (0.7)). The change in lipid concentrations was not related to change in weight. CONCLUSION: Development of diabetes during pregnancy induces a state of dyslipidaemia characterised by elevated triglyceride concentrations, as seen in other insulin resistance states. However, GDM seems to blunt the increase in LDL cholesterol during pregnancy and this requires further investigation. Whether the changes in lipoprotein metabolism in GDM are significant for the health status of the mother and the foetus requires further study.

Serum soluble interleukin-2 receptors as an index of the biological activity of thyroid hormones in hyperthyroidism.

In order to examine whether serum soluble Interleukin-2 Receptors (sIL-2R) could be used as a marker of the biological effects of the thyroid hormones, we measured the sIL-2R, sex hormone binding globulin and beta-2 microglobulin levels in thirty-three hyperthyroid patients (14 with Graves' disease, 17 with Toxic Nodular Goiter and 2 with toxic adenoma) before and during treatment with antithyroid drugs. We found that serum sIL-2R concentrations of the patients, at diagnosis, were significantly higher compared with normal controls (2424 +/- 1447 vs 459 +/- 184 U/ml). All hyperthyroid patients had sIL-2R levels > mean + 2SD of normal controls, with 28 of the 33 patients having sIL-2R concentrations higher than 1011 U/ml (mean + 3SD of normal controls). Only 15 patients had SHBG levels higher than 3SD above the mean for the normal controls and 28 had SHBG levels 2SD above the mean for the normal controls. Three of the 5 hyperthyroid patients with normal SHBG levels at presentation had abnormally high sIL-2R levels. In all patients sIL-2R levels decreased gradually during therapy down to normal levels when euthyroidism was achieved. A strong positive correlation was found between sIL-2R, SHBG and T3 and T4 concentrations. Serum B2-microglobulin (B2-m) levels were higher than the upper normal limit only in 9 patients, but a significant decrement was observed in all patients when euthyroidism was achieved. The above results indicate that serum sIL-2R levels could be a useful marker of the in vivo biological effects of the thyroid hormones on lymphocytes in hyperthyroid patients.

Difference in prevalence of gestational diabetes and perinatal outcome in an innercity multiethnic London population.

In order to establish the prevalence of gestational diabetes mellitus (GDM) among ethnic groups residing in the catchment area of one hospital in central London and to assess both the mode of delivery and the baby outcome, we studied retrospectively 703 women selected for screening for GDM during the years 1991 and 1992. While the prevalence of GDM was approximately 2% overall, within the ethnic groups a significant difference was found with Asians and Africans/Afrocaribbeans being four and two times more likely to have GDM, respectively, than Caucasians (P < 0.001). Both maternal obesity and the diagnosis of GDM influenced the time and the mode of delivery, but perinatal mortality and morbidity did not differ significantly between women with GDM and women with normal glucose tolerance. An association between the GTT glucose area and the gestational age and ethnicity adjusted birth weight was observed in women with normal glucose tolerance test, but was absent in the GDM pregnancies, providing indirect evidence that dietary treatment, with or without insulin treatment, altered the maternal milieu in the latter sufficiently to modify fetal growth.

Ethnic differences in lipid and lipoprotein metabolism in pregnant women of African and Caucasian origin.

AIMS: To investigate differences in serum lipid, lipoprotein and apolipoprotein concentrations in pregnant women of different ethnic origin. METHODS: Serum lipid, lipoprotein and apolipoprotein concentrations were measured in 232 women (114 Caucasians, 118 Africans/Afro-Caribbeans), who presented consecutively for screening for gestational diabetes in the third trimester of pregnancy. RESULTS: African/Afro-Caribbean pregnant women had lower serum concentrations of total cholesterol, low density lipoprotein cholesterol, triglycerides, and apolipoprotein B and higher high density lipoprotein cholesterol and Lp(a) lipoprotein concentrations compared with Caucasian women. Apolipoprotein A1 concentrations were similar in the two groups. The differences were not attributable to differences in weight, age, parity, or postload plasma glucose levels. CONCLUSION: Ethnic origin is an important determinant of serum lipid, lipoprotein and apolipoprotein concentrations during pregnancy.

Ethnic differences in lipid and lipoprotein metabolism in pregnant women of African and Caucasian origin

AIMS: To investigate differences in serum lipid, lipoprotein and apolipoprotein concentrations in pregnant women of different ethnic origin. METHODS: Serum lipid, lipoprotein and apolipoprotein concentrations were measured in 232 women (114 Caucasians, 118 Africans/Afro-Caribbeans), who presented consecutively for screening for gestational diabetes in the third trimester of pregnancy. RESULTS: African/Afro-Caribbean pregnant women had lower serum concentrations of total cholesterol, low density lipoprotein cholesterol, triglycerides, and apolipoprotein B and higher high density lipoprotein cholesterol and Lp(a) lipoprotein concentrations compared with Caucasian women. Apolipoprotein A1 concentrations were similar in the two groups. The differences were not attributable to differences in weight, age, parity, or postload plasma glucose levels. CONCLUSION: Ethnic origin is an important determinant of serum lipid, lipoprotein and apolioprotein concentrations during pregnancy (AU)

Serum lipids, lipoproteins and apolipoproteins in pregnant non-diabetic patients.

AIMS: To investigate the effect of pregnancy on serum concentrations of lipids, lipoproteins, and apolipoproteins. METHODS: Fasting serum concentrations of total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), apolipoproteins AI, AII, and B, and lipoprotein (a) were measured in 178 women with normal glucose tolerance in the second and third trimesters of pregnancy and in a control group of 58 non-pregnant women of similar age. Data were analysed using the unpaired t test and by one-way analysis of variance. RESULTS: The pregnant women had significantly higher concentrations of total cholesterol, triglyceride, LDL cholesterol, HDL cholesterol, and apolipoproteins AI and B (p < 0.001) and apolipoprotein AII (p = 0.003) than the control women. The ratio of apolipoprotein B:apolipoprotein AI was significantly higher in the pregnant women than in the controls (p < 0.001), but the total cholesterol:HDL cholesterol ratio was not significantly different. No significant difference was found in the concentration of lipoprotein (a). CONCLUSIONS: Hyperlipidaemia is common in the second half of pregnancy. This may be a purely physiological response to pregnancy or it may be indicative of pathology in some women. These results warrant a follow up study to investigate whether the hyperlipidaemic response to pregnancy is variable and if so, whether it can predict future hyperlipidaemia in a manner analogous to that of impaired glucose tolerance during pregnancy, predicting non-insulin dependent diabetes in later life.

High levels of serum soluble interleukin-2 receptors in hyperthyroid patients: correlation with serum thyroid hormones and independence from the etiology of the hyperthyroidism.

The serum levels of soluble interleukin-2 receptors (s-IL-2R) and soluble CD8 antigens (s-CD8) were measured in 33 patients with Graves' disease (GD), 29 with toxic nodular goiter (TNG), 6 with toxic adenoma (TA), and 12 with hypothyroidism, as well as in 11 patients with infectious mononucleosis (known to have high s-IL-2R and s-CD8 levels) and 34 normal controls. Serum levels of T3 and T4, both total and free, and of TSH were simultaneously determined. s-IL-2R levels were significantly higher in all patients with hyperthyroidism (mean +/- SD, 3276 +/- 1273 U/mL for GD, 4183 +/- 1832 for TNG, and 1671 +/- 648 for TA) compared to normal control values (P less than 0.001 for GD and TNG and P less than 0.01 for TA), while in the euthyroid state they were within the normal range (535 +/- 240 U/mL). Hypothyroid patients had significantly lower s-IL-2R levels compared to normal controls (P less than 0.05). A positive correlation (P less than 0.001) between serum s-IL-2R levels and total/free T3-T4 levels was found in these groups of patients, while no correlation between s-CD8 levels and s-IL-2R/T3/T4 was found. These findings suggest an association between hyperthyroxinaemia and activation of human lymphocytes in vivo.