Showing papers on "Propylthiouracil published in 2000"

Iodide excess induces apoptosis in thyroid cells through a p53-independent mechanism involving oxidative stress.

Abstract: Thyroid toxicity of iodide excess has been demonstrated in animals fed with an iodide-rich diet; in vitro iodide is cytotoxic, inhibits cell growth, and induces morphological changes in thyroid cells of some species. In this study, we investigated the effect of iodide excess in an immortalized thyroid cell line (TAD-2) in primary cultures of human thyroid cells and in cells of nonthyroid origin. Iodide displayed a dose-dependent cytotoxicity in both TAD-2 and primary thyroid cells, although at different concentrations, whereas it had no effect on cells of nonthyroid origin. Thyroid cells treated with iodide excess underwent apoptosis, as evidenced by morphological changes, plasma membrane phosphatidylserine exposure, and DNA fragmentation. Apoptosis was unaffected by protein synthesis inhibition, whereas inhibition of peroxidase enzymatic activity by propylthiouracil completely blocked iodide cytotoxicity. During KI treatment, reactive oxygen species were produced, and lipid peroxide levels increased mark...

High Prevalence of Antineutrophil Cytoplasmic Antibody Positivity in Childhood Onset Graves’ Disease Treated with Propylthiouracil

Abstract: Propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibody (ANCA)-related vasculitis and nephritis were recently reported in about 30 patients with hyperthyroidism. The objective of this study was to clarify the prevalence of ANCA and the relationship between ANCA and thyroid antibodies in children with Graves' disease. Titers of myeloperoxidase (MPO)-ANCA in sera of 51 patients with childhood onset Graves' disease (16 before treatment, 25 and 10 treated with PTU and methimazole, respectively) were measured by enzyme-linked immunosolvent assay. Antithyroglobulin antibodies (TGAbs) and antithyroperoxidase antibodies (TPOAbs) were also measured by RIA in 25 PTU-treated patients. No patients had clinical manifestations of vasculitis and nephritis. MPO-ANCA was positive in 6.7% of patients before treatment and in 64.0% of those treated with PTU and in none of those treated with methimazole. MPO-ANCA had a significantly positive correlation with TGAbs (P < 0.05) and no significant correlation with TPOAbs. These findings show the high prevalence of the MPO-ANCA positivity in PTU-treated childhood onset Graves' disease, suggesting that PTU may not be preferred as the first line for the treatment of children with Graves' disease. The significant correlation between MPO-ANCA and TGAbs indicates that the severity of Graves' disease may be a factor responsible for the MPO-ANCA positivity. The cross-reactivity between MPO-ANCA and TPOAbs may not play a role in the high prevalence of MPO-ANCA in the patients exposed to PTU.

Treatment with propylthiouracil is associated with appearance of antineutrophil cytoplasmic antibodies in some patients with Graves' disease.

Abstract: The use of propylthiouracil (PTU) for the treatment of Graves' disease is associated with few adverse effects such as skin eruptions, liver dysfunction, and agranulocytosis. Furthermore, recent studies described the development of antineutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis and vasculitis in patients treated with PTU. Here we investigated whether PTU therapy per se is associated with the appearance of ANCA in patients with Graves' disease. We analyzed 119 serum samples from 117 patients with Graves' disease treated with either PTU (n = 56), or methimazole (MMI) (n = 21), as well as untreated patients (n = 42). Myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA were tested by enzyme-linked immunosorbent assay (ELISA) kits. MPO-ANCA was negative in all patients treated with MMI therapy and untreated patients. However, MPO-ANCA was detected in 21 (37.5%) of 56 patients treated with PTU therapy. Furthermore, two patients who were negative for MPO-ANCA became positive after PTU therapy. The proportion of patients positive for MPO-ANCA increased with the prolongation of PTU therapy, but did not correlate with age, gender, and positive antithyroperoxidase (TPO) antibody. Among 21 MPO-ANCA positive patients, 12 had no symptoms, but 9 patients complained of myalgia, arthralgia, or common cold like symptoms after the appearance of MPO-ANCA. Three patients developed agranulocytosis or granulocytopenia, but none showed abnormal urinary findings. Our results suggest that PTU per se is associated with the production of MPO-ANCA in patients with Graves' disease.

Thyroid function in wholly breast-feeding infants whose mothers take high doses of propylthiouracil.

Abstract: BACKGROUND Propylthiouracil (PTU) might theoretically be preferred over methimazole (MMI) during breast-feeding because of its lower milk/serum concentration ratio (0.1 vs. 1.0). The problem is that Graves' disease often relapses during the postpartum period, and high doses of PTU are sometimes needed to control maternal hyperthyroidism) during breast-feeding. However, there are virtually no data on the effects of maternal PTU on thyroid status of infants whose mothers take more than 300 mg PTU daily and who are wholly breast-feeding. OBJECTIVES To investigate whether mothers can breast-feed without adverse effects on infants' thyroid status while taking 300 mg or more daily of PTU . SUBJECTS AND DESIGN Eleven infants who were wholly breast-fed while their mothers took PTU 300–750 mg daily for Graves' hyperthyroidism were included in this study. In one of the 11 infants, the mother also took iodine 6 mg daily for a limited period. Thyroid status in these infants was evaluated. MEASUREMENTS Free T4 (FT4), thyrotrophin (TSH), and TSH binding inhibiting antibody (TBIAb) concentrations were examined at least once in the age range 6 days to 9 months. Maternal blood was also examined for FT4 and TBIAb on the same day, or within a week, of the infants' blood tests. FT4, TSH and TBIAb concentrations at birth were examined, using cord blood, in cases where antithyroid drugs had been continued through delivery. RESULTS Three of the 11 infants had TSH concentrations higher than the normal range for adults. In one of the three infants, the TSH concentration, which was determined 19 weeks after birth, was just above the normal range. In the remaining two infants whose mothers had taken PTU through delivery, TSH concentrations, determined within 7 days after birth, were distinctly high, but they became normal while maternal PTU doses were the same as or higher than those at the initial examination. Maternal PTU doses or FT4 concentrations were not significantly correlated with infants' TSH concentrations. CONCLUSION Mothers can breast-feed while taking propylthiouracil at doses as high as 750 mg daily without adverse effects on thyroid status in their infants.

Preliminary validation of a short-term morphological assay to evaluate adverse effects on amphibian metamorphosis and thyroid function using Xenopus laevis.

Abstract: Short-term static-renewal studies were performed on Xenopus laevis embryos with 16 selected test materials from day 50 (stage 60) to day 64 (stage 66) (14-day test) to evaluate effects on tail resorption and thyroid function. Of the 16 test materials, nine were found to inhibit significantly the rate of tail resorption, four were found to stimulate metamorphosis and three had no appreciable effect on the rate of metamorphosis. In an effort to determine if the morphological effects observed were related to alteration in thyroid activity, measurement of triiodothyronine (T3) in the test organisms and coadministration studies using thyroxine (agonist) or propylthiouracil (antagonist) were performed based on the morphological response noted during tail resorption. Of the nine compounds found to inhibit the rate of tail resorption, six were found to reduce the levels of T3. In each case, the inhibitory response could be at least partially alleviated by the co-administration of thyroxine. Larvae exposed to the four stimulatory agents had somewhat elevated levels of T3 and were responsive to propylthiouracil antagonism. These results suggest that 12 of the 14 compounds tested in this study that altered the rate of tail resorption did so via the thyroid axis. Overall, the X. laevis model appeared to be a suitable system for evaluating the impact of environmental agents and chemical products on thyroid function.

Increased levels of serum interleukin-18 in Graves' disease.

Abstract: We have previously reported that serum soluble interleukin-2 receptor (sIL-2R) and IL-12 levels were significantly increased in hyperthyroid Graves' disease. In this study, we investigated serum IL-18 levels in patients with either Graves' disease or Hashimoto's thyroiditis. The serum IL-18 levels in Graves' disease were significantly increased in the hyperthyroid state and were decreased during treatment with methimazole or propylthiouracil. On the other hand, the levels in Hashimoto's thyroiditis in the hypothyroid state showed no significant differences from those in healthy subjects. When liothyronine sodium was administered orally to healthy subjects, serum IL-18 levels were not changed. Positive correlations between serum IL-18 and IL-12, IL-12 and sIL-2R, and sIL-2R and IL-18 levels were noted in Graves' disease. These results suggest that Th1 cytokines might play an important regulatory role in Graves' disease.

Excess Iodine Induces Apoptosis in the Thyroid of Goitrogen-Pretreated Rats In Vivo

Abstract: Previously, we observed that excess iodide rapidly suppressed the elevated ornithine decarboxylase activity in the thyroid of propylthiouracil (PTU)-pretreated rats. Excess iodide also induces involution of goitrous thyroids. These findings led us to study effects of excess iodide on apoptosis of rat thyroids. When given to PTU-pretreated rats, excess potassium iodide (KI) (13 mg/kg body weight, 10 mg as iodine) induced DNA fragmentation in the thyroid at the first 3 hours after its treatment. The percentage of DNA fragmentation was also maximal at 3 hours after KI treatment. In methimazole-pretreated rats, the kinetic of DNA fragmentation was nearly the same; apoptosis increased for the first 6 hours and then decreased at 12 hours after KI administration. Other iodinated compounds such as amiodarone and diiodotyrosine have also shown apoptosis-inducing activity, but their effect was observed later than KI. Iopanoic acid had no such effect. Apoptotic changes were also observed with the use of flow cytometry. PTU or methimazole alone had some stimulatory effect on thyroid apoptosis. Iodine effect was not observed in rats treated with either perchlorate or thiocyanate. These results suggest that excess iodine induces thyroid involution in goitrogen-treated rats at least partially by apoptosis.

Myeloperoxidase-antineutrophil cytoplasmic antibody-associated vasculitis following propylthiouracil therapy.

Abstract: q 2000 British Association of Dermatologists, British Journal of Dermatology, 142, 812±851 The use of cyclosporin, which has significant benefit in the management of PG, helped us to stop the progression of lesions and allowed the avoidance of steroids during pregnancy, and reduced pain as a noteworthy secondary benefit. However, the relapse after reducing the dose of cyclosporin demonstrates the necessity of an adequate dose, which can be up to 10 mg kg daily, as stated by Chow and Ho. As our patient underwent a Caesarian section for delivery, we were anxious regarding the possibility of the `pathergic phenomenon' in the scar, as described by Harland et al. but this risk was presumably abolished by the systemic treatment she received.

Effects of propylthiouracil treatment on antioxidant activities in blood of toxic multinodular goiter patients.

Abstract: Erythrocyte, serum and plasma antioxidant activities and the effects of propylthiouracil (PTU) treatment on these activities were studied in patients with toxic multinodular goiter. The activities of the erythrocyte antioxidant enzymes (glucose-6-phosphate dehydrogenase, catalase, Cu/Zn-superoxide dismutase, selenium (Se)-dependent glutathione peroxidase and glutathione reductase) and the levels of erythrocyte Se, serum ceruloplasmin and plasma malondialdehyde were significantly higher while serum vitamin E, plasma vitamin C and plasma Se were lower in hyperthyroid patients. PTU treatment, not for 1 but for 3 months caused a partial reversal of antioxidant activities to euthyroid levels. It is suggested that alterations in blood antioxidant activities following PTU treatment might be due to the antioxidant and/or antithyroid effect of this drug.

Direct effects of propylthiouracil on testosterone secretion in rat testicular interstitial cells.

Abstract: The aim of this study was to investigate the mechanism by which propylthiouracil (PTU) exerts its inhibitory effects on the production of testosterone by rat testicular interstitial cells. The plasma testosterone concentration was decreased 60 and 120 min after an intravenous infusion of PTU (10 or 20 mg kg−1), but the concentration of plasma T4 was unaffected by the drug treatment. Exposure of anterior pituitary tissue to PTU (3–12 mM) in vitro did not affect either basal or gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release. PTU (3–12 mM) inhibited both the basal and the human chorionic gonadotropin (hCG, 0.05 iu ml−1)-stimulated release of testosterone from rat testicular tissue in vitro; at the highest concentration tested (12 mM), it also inhibited the forskolin or 8-bromo-adenosine 3′:5′-cyclic monophosphate (8-Br-cyclic AMP)-stimulated release of testosterone. The 25-OH-cholesterol (10−7–10−5 M)-stimulated release of pregnenolone and testosterone by the testicular interstitial cells was inhibited by PTU (12 mM, P<0.05). The results suggest that the inhibitory actions of PTU on testosterone secretion are exerted, at least in part, at the testicular level through a mechanism which is independent of thyroid status and which involves a reduction in P450scc activity and, hence, in the conversion of cholesterol to pregnenolone. British Journal of Pharmacology (2000) 130, 1477–1482; doi:10.1038/sj.bjp.0703444

Developmental change in Na, K-ATPase α1 and β1 expression in normal and hypothyroid rat renal cortex

Abstract: Renal Na,K-ATPase drives active reabsorption of sodium and cotransported solutes along the nephron. There is a large increase in net Na+ reabsorption in the postnatal rat kidney. It has previously been established that the postnatal increase in expression of sodium pump isoforms in the brain, but not the heart, is blunted in the hypothyroid neonate. The aims of this study were to establish whether the developmental increase in renal sodium transport is associated with coordinate increases in the abundance of the sodium pump α1 catalytic and β1 glycoprotein subunits and Na,K-ATPase activity, and to determine whether thyroid status influences the postnatal increase in renal Na,K-ATPase expression. Pregnant rats were made hypothyroid with low iodine diet, propylthiouracil and perchlorate. Offspring were hypothyroid assessed by triiodothyronine/thyroxine RIA. Renal cortical membranes were prepared from euthyroid and hypothyroid rats from 6 to 24 days of age. There was no change in Na,K-ATPase activity or expression between 6 and 15 days. Between 15 and 24 days, Na,K-ATPase activity increased 1.35-fold while sodium pump α1 and β1 subunit abundance increased coordinately to 1.7- and 2-fold over the previous period, respectively. In hypothyroid neonates, kidney weight was less than in euthyroids, and Na,K-ATPase activity, α1 and β1 subunit pool sizes did not significantly increase as a function of age between 6 and 24 days. We conclude that the postnatal increase in sodium pump activity can be accounted for by coordinate increases in the pool sizes of α1 and β1 subunits and that, like in brain, this increased Na,K-ATPase expression is dependent on normal thyroid status.

Plasma homocysteine is decreased in the hypothyroid rat.

Abstract: Recent clinical studies have indicated that plasma homocysteine was significantly increased in hypothyroid patients. Since hyperhomocysteinemia is an independent risk factor for cardiovascular disease we investigated homocysteine metabolism in hypothyroid rats. Hypothyroidism was induced in one study by addition of propylthiouracil (PTU) to the drinking water for 2 weeks. In a second study, thyroidectomized and sham-operated rats were used with thyroid hormone replacement via mini-osmotic pumps. Unlike the human hypothyroid patients, both groups of hypothyroid rats exhibited decreased total plasma homocysteine (30% in PTU rats, 50% in thyroidectomized rats) versus their respective controls. Thyroid replacement normalised homocysteine levels in the thyroidectomized rat. Increased activities of the hepatic trans-sulfuration enzymes were found in both models of hypothyroidism. These results provide a possible explanation for the decreased plasma homocysteine concentrations. The hypothyroid rat cannot be used...

Evidence for the presence of 5'-deiodinase in mammalian seminal plasma and for the increase in enzyme activity in the prepubertal testis.

Abstract: Thyroid hormones are critical for structural and functional development of the testis and Sertoli cells are considered true target cells for triiodothyronine (T3). However, the role of thyroid hormones in the adult testis seems to be minimal and the mechanism by which they affect testicular function is not known. Due to the existing blood-testis barrier the concentration of thyroid hormones in seminal plasma is kept lower than in blood plasma. We have found that T3 may reach the testis not only from the circulation but also from local enzymic conversion of thyroxine to T3. The presence of the enzymic activity responsible for thyroxine 5'deiodination and for generating T3 locally was also found in boar's seminal plasma. The seminal plasma 5'-deiodinase (5'-D) appeared to be predominantly the propylthiouracil (PTU)-insensitive type II isoenzyme found, so far, in tissues where it plays a role in paracrine signalling. It contains selenocysteine in its molecule (inhibition by aurothioglucose), and has an apparent Km for reverse-T3 as substrate of 0.36 nM and a Vmax 23.8 fmol I-/mg protein/min. Because the seminal plasma 5'-D is partially, but uncompetitively, inhibited by PTU, the presence in seminal plasma of two 5'-D isoenzymes (type I and II) cannot be excluded. The 5'-D activity in testes increased significantly between week 3 and 4, and this increase was concomitant with increase in testicular size. The relationship between testicular weight gain and age showed a similar characteristic change and corresponded to the change in 5'-D activity. Unlike in rodents, the testis of the prepubertal pig has thyroid hormone receptors in Sertoli cells, and suggests that in growing piglets, testicular 5'-D is a key factor regulating local supply of biologically active T3, and is an essential factor in testicular paracrine function. The present results are the first demonstration and characterization of the 5'-deiodinase in seminal plasma.

Disseminated intravascular coagulation and vasculitis during propylthiouracil therapy.

Abstract: The use of antithyroid drugs in the early 1940s revolutionised the management of hyperthyroidism. Since their introduction, a variety of adverse reactions, including haematological, dermatological, and rheumatological effects, have been associated with these drugs. The incidence of these side-effects is similar to many other commonly used drugs, ie, 1–5%.1 The most common side-effects include skin rash, fever, arthralgias/arthritis and neutropenia while lupus-like reaction, vasculitis, hepatitis, agranulocytosis and thrombocytopenia are uncommon.2 Disseminated intravascular coagulation (DIC) is a rare adverse effect of propylthiouracil therapy.3 Herein we report a case of DIC and vasculitis following a short course of propylthiouracil therapy. A 42-year-old African-American woman with Grave's disease, diagnosed 20 years earlier, had received propylthiouracil (100 mg tid) for the past 2 weeks because of recent exacerbation of symptoms. She was admitted to the hospital because of sudden onset of palpable purpuric rash, which started on the face and later spread to her trunk and extremities. Laboratory test results on admission disclosed the following data: haemoglobin 12.2 g/dl, haematocrit 37.8, white blood cells 15.5 × …

The roles of thyroid hormones and prolactin in the control of fibre moult and associated changes in hair follicle activities in cashmere goats

Abstract: Five groups of 8 adult male castrated goats were used in an 8-month study. For a 6-month period commencing in November, goats of one group were dosed with propylthiouracil (PTU), a drug which reduces the rate of conversion of thyroxine (T4) to triiodothyronine (T3) in peripheral tissues. Animals of a second group were treated with bromocriptine (Br), a drug which reduces the circulating concentrations of prolactin. Animals of other groups were treated with PTU + Br, PTU + triiodothyronine (PTU + T3), or vehicle only (control). The mean date of moult onset was later in animals of the PTU + T3 (P < 0.05), PTU + Br (P < 0.05), and Br (P < 0.01) groups than in control animals. PTU + T3 , PTU + Br, and Br animals also exhibited lower minimum levels of primary follicle activity than control animals (P < 0.01). On the basis of a periodic function applied to the data, there was a trend towards a later nadir of both primary and secondary follicle activity. There were no significant effects of treatment on profiles of thyroxine (T4), triiodothyronine (T3), growth hormone (GH), insulin-like growth factor-1, or insulin but a significant (P < 0.001) seasonal increase in mean concentration occurred between November and March–April in all except GH profiles. It is concluded that PTU and Br did not act additively or synergistically on follicle activity or moult. Nevertheless, it is further concluded that the mechanisms of action of the thyroid hormones and prolactin are not independent and that future studies of their effects on follicle function should address their interactions with other hormones and changes in thyroid hormone receptor activity within the follicles.

Efficacy of oral iodide therapy on neonatal hyperthyroidism caused by maternal Graves' disease.

Abstract: Objective: To verify the efficacy of oral iodide therapy in treating a case of early neonatal hyperthyroidism due to maternal Graves’ disease. Methods: We report

Thyroid-stimulating antibody in a patient with euthyroid Graves' disease.

Abstract: We report an 11-year-old girl with euthyroid Graves' disease. She was referred to our clinic because of left exophthalmos without other symptoms suggestive of hyperthyroidism. Her serum concentration of free thyroxine (FT4) and free triiodothyronine (FT3) were normal, but thyroid-stimulating hormone (TSH) was below normal and impaired TSH response to TSH releasing hormone (TRH) was found. Although the sera were positivefor anti-TSH receptor antibody (TRAb) and thyroid-stimulating antibody (TSAb), both titers were not as high as usually observed in Graves' disease. Three months later, she developed hyperthyroidism and was treated with propylthiouracil. Within 2 weeks of the initiation of therapy, all symptoms except exophthalmos disappeared, and after 2 months of treatment TRAb was negative though TSAb remained positive. TSAb is therefore a good indicator to use in the diagnosis and follow-up of euthyroid Graves' disease and should be measured in patients with exophthalmos of unknown origin, even in children.

Direct effects of propylthiouracil on testosterone production in monkeys.

Abstract: Propylthiouracil (PTU) is an anti-thyroid drug. However, the direct effects of PTU on the endocrine functions of non-thyroid glands are unclear. In the present study, we examined the acute effects of PTU on testosterone secretion in monkeys. Male monkeys were infused intravenously with PTU for 30 min. Blood samples were collected at several time intervals. Monkey testicular interstitial cells were cultured with PTU, human chorionic gonadotropin (hCG), or forskolin, at 34 degrees C for 1 h. In another study, steroidogenesis in monkey testicular interstitial cells were examined. PTU decreased plasma testosterone but not plasma thyroxine (T4) and luteinizing hormone (LH) levels in monkeys. Administration of PTU resulted in a dose-dependent inhibition of basal and hCG-, as well as forskolin-stimulated testosterone release by monkey testicular interstitial cells. PTU also diminished the stimulatory effects induced by androstenedione. These results suggest that PTU inhibits testosterone secretion via a mechanism independent of the secretion of T4 and LH in primates. The inhibitory mechanism of PTU on testosterone production involves a decreased activity of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) and post-cAMP pathways.

Myeloperoxidase antineutrophil cytoplasmic antibody positive vasculitis during propylthiouracil treatment : Successful management with oral corticosteroids

Abstract: implicated as a diagnostic marker for several vasculitic disorders.1 Two major auto-antigens within neutrophils have been identified: proteinase 3 (PR3) and myeloperoxidase (MPO). Recently, MPO-ANCA-positive vasculitis has been documented as a complication of propylthiouracil (PTU) treatment;2–6 however, only two of the approximately 20 reported patients2–6 were pediatric patients under 15 years of age at diagnosis3 and discussion of the significance of this complication has focused mainly on the irreversible renal failure due to crescentic glomerulonephritis.3 We report the findings from the case of a 15-year-old girl with PTU-induced ANCA-associated vasculitis with marginal renal damage, who was successfully treated with oral corticosteroids. We also discuss the therapeutic approach to PTU-induced vasculitis.

[Myeloperoxidase-antineutrophil cytoplasmic antibody positive alveolar hemorrhage during propylthiouracil therapy for hyperthyroidism].

Abstract: A 62-year-old woman had been treated with propylthiouracil(PTU) for hyperthyroidism. Because bloody sputum, dyspnea, and severe hypoxemia developed, the patient was admitted to our hospital. Chest X-ray and chest computed tomographic (CT) films disclosed diffuse infiltrative shadows in both lung fields. Bronchoalveolar lavage revealed abundant hemosiderin-laden macrophages. Alveolar hemorrhage associated with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) positive vasculitis syndrome was diagnosed because of the high serum level of MPO-ANCA. After the initiation of steroid therapy and termination of PTU, the infiltrative shadows in both lung fields disappeared, PaO2 improved, and MPO-ANCA decreased. There have been some reports of MPO-ANCA positive vasculitis syndrome developing during PTU therapy, but most were concerned with renal disease. We concluded that PTU and similar agents should be given consideration as one of the possible causes of MPO-ANCA-induced alveolar hemorrhage.

Altered CD15 glycolipid expression in the developing rat cerebellum following treatment with antithyroid drug, propylthiouracil.

Abstract: Thyroid hormone plays an important role during central nervous system (CNS) development. Experimentally-induced perinatal hypothyroid rats show abnormal cerebellar cytoarchitecture, but the underlying mechanism is not fully understood. Altered cell-cell interactions may contribute to such abnormalities, since the expression of NCAM is increased in hypothyroid animals. In the present study, we examined the expression of carbohydrate epitope 3-fucosyl-N-acetyl-lactosamine (CD15 antigen), that can be localized on both astrocytes and neurons in the developing brain, and is considered to play an important role in glial-neuronal interaction and cell migration. Newborn rats were treated with an antithyroid drug, propylthiouracil (PTU) and the CD15 glycolipid levels in the cerebellum were examined by enzyme-linked immunosolvent assay (ELISA) using 7A monoclonal antibody raised against rat forebrain antigen. A transient elevation of CD15 level was observed on postnatal day 10 in PTU-treated animals. Analysis of neutral glycolipids on high performance thin layer chromatography (HPTLC), revealed two distinct immunoreactive bands, corresponding to Fuc-nLc6 and Fuc-nLc4. The Fuc-nLc4 is preferentially increased in the PTU-treated group. These results suggest that a transient increase in CD15 glycoconjugates with isoform-specific manner induced by PTU may contribute to morphological abnormalities in hypothyroid rat cerebellum affecting granule cell migration.

Thyroid disease in pregnancy

Abstract: Thyroid disease is common in the childbearing years. It impairs fertility and, if untreated, greatly increases risks of complications in pregnancy. The physiological changes of pregnancy place stresses on the thyroid axis, but most women adapt to these and remain euthyroid. This article will assist GPs managing patients with thyroid disease during pregnancy and in the postpartum period.Key Points• In pregnant women, thyroid function tests should be checked every six to eight weeks in hypothyroidism and every four to six weeks in hyperthyroidism.• Thyroid stimulating antibodies cross the placenta and may produce fetal and neonatal hyperthyroidism, and should be measured during the first and third trimesters.• Propylthiouracil and carbimazole are safe in pregnancy and in breastfeeding.• Beware of patients with a past history of thyroid ablation for Graves’ disease – the fetus may still be affected by maternal antibodies crossing the placenta.• Patients with postpartum thyroid disease are at increased risk of developing permanent hypothyroidism and should have annual thyroid function tests.

The rat hepatic lectin-1 subunit of the asialoglycoprotein receptor is upregulated by thyrotropin and downregulated by neoplastic transformation of thyroid cells.

Abstract: We have recently shown that the rat hepatic lectin (RHL)-l subunit of the asialoglycoprotein receptor (ASGPr) is expressed in the PC C13 differentiated thyroid cell line. To investigate in vivo the expression of RHL-1 and the ability of thyrotropin (TSH) to modulate its expression, reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blot assays have been performed on thyroid extracts from rats treated with thyroxine (T4) or propylthiouracil (PTU), each of which modulates TSH levels. It is shown that RHL-1 expression is down-regulated by T4 (which decreases serum TSH) and upregulated by PTU (which increases serum TSH), at both mRNA and protein levels. The sensitivity of RHL-1 to neoplastic transformation of thyroid cells has been investigated. The RHL-1 expression pattern has been studied in PC C13 thyroid cells transformed by several oncogenes that induce different degrees of malignancy and dedifferentiation. RT-PCR and Western blot assays show that RHL-1 expression progressively decrease...