bluuebunny/crossref_metadata_2025 huggingface dataset:
Salmonella brandenburg: a novel cause of acute suppurative thyroiditis
Authors: Chiovato Luca , Canale Giuseppe , Maccherini Doretta , Falcone Valeria , Pacini Furio , Pinchera Aldo
Published: June 2009

A patient with suppurative thyroiditis due to infection with Salmonella brandenburg is reported. Localization of the infection occurred to a pre-existing thyroid nodule after Salmonella bacteremia. S. brandenburg was isolated in pure culture from the fluid obtained by needle aspiration of the suppurated thyroid nodule. Surgical drainage followed by subtotal thyroidectomy was required to cure the disease. No evidence of pyriform sinus fistula was found. Suppurative thyroiditis due to Salmonella ubiquitous serotypes is an extremely rare condition, and infection to the thyroid produced by S. brandenburg is reported now for the first time. Indeed, the isolation rate of S. brandenburg from all human sources is low, and this microorganism is an uncommon agent of bacteremia.
Establishment of the second international standards for porcine and human calcitonins: report of the international collaborative study
Authors: Zanelli Joan M , Gaines-Das Rose E , Corran P
Published: June 2009

The biological potency of calcitonins in clinical use in long-term treatment of Paget's disease of bone and, increasingly, in osteoporosis is usually expressed in international units defined by the relevant World Health Organization international reference preparation. The international reference preparations for porcine and human calcitonins were ampouled in 1970 and stocks are now exhausted. Replacement standards were ampouled in 1989 and have been evaluated and calibrated by an international collaborative study comprising 16 laboratories in 12 countries. Evaluations included high-performance liquid chromatography and in vitro bioassay; calibration of each new ampouled preparation in terms of its international reference preparation was by in vivo rat hypocalcaemia bioassay. On the basis of the results of the study and with the agreement of the participants, replacement standards were established by the Expert Committee on Biological Standardization of the World Health Organization in 1991: the international standard for porcine calcitonin (ampoule code 89/540), with an assigned potency of 0.8 international units per ampoule, and the international standard for human calcitonin, with an assigned potency of 17.5 international units per ampoule. Both international standards appeared to be sufficiently stable to serve as the international standards for in vivo biological assays. Comparison of the two species of calcitonin in the same hypocalcaemia assay showed that they were approximately equipotent when the doses were given intravenously but that the human peptide was four- to sixfold more potent than porcine calcitonin when doses were given subcutaneously, emphasizing the need to compare "like with like".
The divergent effect of RU 486 on adrenal function in the dog is related to differences in its pharmacokinetics
Authors: Spitz Irving M , Heikinheimo Oskari , Wade Charles E
Published: June 2009

This study has evaluated the relationship between the antiglucocorticoid effect of RU 486 and its pharmacokinetics in seven female mongrel dogs (weight 21–30 kg), all of which had appropriate responses to insulin-induced hypoglycemia and metyrapone. They were given RU 486 (50 mg·kg−1·d−1) for ten days. Three dogs (responders) demonstrated increased secretion of ACTH and cortisol which reached a maximum at the termination of RU 486 administration and returned to baseline by days 22 and 18, respectively. The remaining four dogs (non-responders) showed only transient non-sustained increases in ACTH and cortisol. Serum concentrations of RU 486 and its mono-demethylated and di-demethylated (but not its hydroxylated) metabolites were significantly higher in the responder dogs. The ratios of the hydroxylated metabolite to RU 486 and its demethylated derivatives were higher in the non-responders, whereas the ratio of the di-demethylated to mono-demethylated compound was higher in the responders. Since variations in the hydroxylation and reductive catabolism of steroids have been well documented in different strains of a species, it is possible that the differences in levels of RU 486 and its metabolites in the two groups are accounted for by variations in RU 486 metabolism. In the responder group the metabolism of RU 486 is directed to demethylation, and in the non-responder group to hydroxylation. Thus, differences in pharmacokinetics of RU 486 in the two groups of dogs may explain the variable biological response to this antiglucocorticoid.
A re-evaluation of the anabolic effect of testosterone in rats: interactions with gonadectomy, adrenalectomy and hypophysectomy
Authors: Woodward Christopher JH
Published: June 2009

Growth and body composition were determined in rats implanted with silastic tubes containing testosterone. The implant (i) had no effect on growth in intact males, (ii) restored the sub-normal weight gain of gonadectomized males to normal (+ 30%; p<0.01), (iii) substantially increased weight gain in intact females (+ 172%; p<0.001), and (iv) caused a further increase (+32%; p<0.01) in the accelerated weight gain resulting from ovariectomy. In intact animals of both sexes, testosterone caused significant atrophy of the reproductive tissues; this was accompanied in females by reduced plasma estradiol concentrations. Thus the large effect of testosterone on growth in intact females is probably due to diminished secretion of ovarian estradiol, and is distinct from the smaller effect observed in castrated animals of both sexes. To investigate the mechanism underlying the latter response, testosterone was implanted in rats which had been both adrenalectomized and gonadectomized, and also in hypophysectomized animals. In each case a significant anabolic effect was observed, showing that the response requires neither adrenal nor pituitary glands. In all experiments, increased body weights resulting from testosterone treatment consisted at least partly of fat-free mass.
Recovery from lymphocytic hypophysitis associated with painless thyroiditis: clinical implications of circulating antipituitary antibodies
Authors: Ozawa Yasunori , Shishiba Yoshimasa
Published: June 2009

Lymphocytic hypophysitis usually occurs in the antepartum or postpartum period and recovery of pituitary dysfunction has not been documented in most cases reported previously. We present a 50-year-old woman with lymphocytic hypophysitis who spontaneously recovered from panhypopituitarism over 18 months with the disappearance of an intrasellar mass. Although lymphocytic hypophysitis is thought to be an autoimmune disease, the clinical and pathogenetic significance of circulating antipituitary autoantibodies has not been clarified. Antipituitary antibodies were studied by immunofluorescence in blood samples obtained during the whole clinical course in this particular patient. Antibodies against rat pituitary cytosol were positive during the period of hypopituitarism and became negative when pituitary function recovered. Antibodies reacting with intact prolactin-secreting rat GH3 and corticotropin-secreting mouse AtT-20 cells were also positive during her period of hypopituitarism. They remained positive for several years after the recovery of pituitary function. We conclude that circulating antibodies against rat pituitary cytosol are good markers of pituitary inflammation in this patient. The other point to be emphasized in this case is the simultaneous development of painless thyroiditis and lymphocytic hypophysitis. We have discussed the pathogenic relationship of these two diseases on the basis of similar cases reported previously.
Plasma levels of corticotropin-releasing hormone in hypothalamic—pituitary—adrenal disorders and chronic renal failure
Authors: Hashimoto Kozo , Nishioka Tatsuya , Numata Yukiko , Ogasa Takashi , Kageyama Jingo , Suemaru Shuso
Published: June 2009

Plasma levels of corticotropin-releasing hormone (CRH) were measured in hypothalamic-pituitary-adrenal disorders and chronic renal failure to investigate the clinical significance of plasma CRH. The mean plasma CRH level in normal subjects (N=26) was 1.64±0.43 pmol/l (normal range 0.77–2.5 pmol/l). Four of six patients with hypothalamic disorders receiving hydrocortisone supplementation had a low plasma CRH level. Two of six patients with Sheehan's syndrome had a low plasma CRH level whereas one patient had a high plasma CRH level. Two patients with Cushing's syndrome had a low plasma CRH level whereas two patients with Cushing's disease had a normal plasma CRH level. Six of 19 patients receiving prednisolone therapy had a low plasma CRH level. The mean plasma CRH level in this group was 0.97±0.34 pmol/l, which is significantly lower than that in the normal group. In this group, significant correlation was seen between plasma CRH and adrenocorticotropin levels. Eleven of 21 patients with chronic renal failure undergoing hemodialysis had a high plasma CRH level. Just after hemodialysis the plasma CRH levels decreased in 15 of 20 patients, while plasma adrenocorticotropin and cortisol levels increased in 13 of 19 patients and in 15 of 20 patients, respectively. Immunoreactive CRH in plasma measured both before and after hemodialysis eluted similarly on reversed-phase high-performance liquid chromatography. These results suggest that the plasma CRH level is at least partially suppressed by a chronically elevated plasma glucocorticoid level and that CRH in plasma is partially removed by hemodialysis.
Endocrine function following single fraction and fractionated total body irradiation for bone marrow transplantation in childhood
Authors: Thomas BC , Stanhope R , Plowman PN , Leiper AD
Published: June 2009

Forty-nine children who had undergone treatment with cyclophosphamide and total body irradiation before bone marrow transplantation were investigated for impaired endocrine function. Twenty-six patients received single fraction total body irradiation as a dose of 9–10 Gy, whereas 23 patients received fractionated total body irradiation as a total dose of either 12 Gy divided into six fractions or 14.4 Gy divided into eight fractions, administered over 3 or 4 days. Half of the patients in the single fraction group and nine in the fractionated group had received cranial irradiation prior to total body irradiation. Pathological changes in thyroid function were observed in 19 patients (73%) of the single fraction group (elevated thyrotrophin (58%) and decreased thyroxine levels (15%)). whereas in the fractionated group only six patients (25%) developed transient raised thyrotrophin levels; the mean observation period was 3.2 years in the single fraction group and 2.7 years in the fractionated group. The stimulated growth hormone peak concentration was influenced significantly by previous cranial irradiation and was independent of the type of total body irradiation administered. In the patients who had received cranial irradiation, the mean growth hormone peak levels were 8.4 mU/l (single fraction group) and 13.9 mU/l (fractionated group), whereas in those who received only total body irradiation they were 24.9 mU/l (single fraction group) and 28.1 mU/l (fractionated group). The basal gonadotrophin concentration in children older than 9 years showed elevated levels in nine patients (50%) of the single fraction group and in only three patients (30%) of the fractionated group. A further 10 patients (38%) in the single fraction group and one girl (10%) in the fractionated group demonstrated abnormal stimulated follicle stimulating hormone levels.
Insulin-like growth factors (IGF) I and II and IGF binding proteins 1, 2 and 3 during low-dose growth hormone (GH) infusion and sequential euglycemic and hypoglycemic glucose clamps: studies in GH-deficient patients
Authors: Jorgensen Jens OL , Blum Werner F , Horn Nanette , Møller Niels , Møller Jens , Ranke Michael B , Christiansen Jens S
Published: June 2009

To evaluate the short-term effects of growth hormone (GH), insulin and different levels of glycemia on insulin-like growth factors (IGF) I and II and IGF binding proteins (IGFBP) 1, 2 and 3, we studied six GH-deficient adolescents during a night and the following day in the postabsorptive (basal) state followed by sequential euglycemic (5 mmol/l) and hypoglycemic (3 mmol/l) glucose clamps concomitant with an intravenous infusion (starting at 24.00 h) of GH (35 μg/h) or saline. Current GH therapy was withdrawn 24 h prior to each study. Nocturnal levels of IGF-I, IGF-II, IGFBP-2 and IGFBP-3 remained stable during both studies. Nocturnal serum IGFBP-1 increased and correlated inversely with insulin in both studies. Regression analysis revealed a significant inverse correlation between mean nocturnal IGFBP-2 and IGFBP-3 levels. During the daytime, serum IGF-I declined slowly during saline infusion, whereas serum IGF-II remained stable in both studies. Serum IGFBP-1 displayed a gradual significant decline during the basal state and the euglycemic and hypoglycemic clamps seemed to be unaffected by GH levels. By contrast, serum IGFBP-2 remained stable during the same period in both the GH and the saline study. Serum IGFBP-3 declined insignificantly during the daytime in the saline study. In conclusion: a strong inverse correlation between IGFBP-1 and insulin is confirmed; serum IGFBP-2 exhibits a constant circadian pattern, which seems independent of both ambient glucose and insulin levels and short-term GH deprivation but, on the other hand, shows a strong inverse correlation with IGFBP-3 levels; it is possible that IGFBP-2 levels are regulated by IGFBP-3 or IGFBP-3 binding site availability.
Coordinate activation of the corticotropic axis by insulin-induced hypoglycemia: simultaneous estimates of β-endorphin, adrenocorticotropin and cortisol secretion and disappearance in normal men
Authors: Iranmanesh Ali , Lizarralde German , Veldhuis Johannes D
Published: June 2009

In the present study, we investigated the coordinate kinetic response of the corticotropic axis to the acute metabolic stress of hypoglycemia by applying deconvolution analysis to adrenocorticotropin (ACTH), β-endorphin and cortisol concentration-time series generated in seven normal men after intravenous administration of insulin. Hypoglycemic stress resulted in a 22-fold increase in the mean plasma concentration of ACTH to a maximum of 77±15 pmol/l, in conjunction with a 7.5-fold increase in the mean plasma β-endorphin concentration, the maximal value of which was 96±11 pmol/l. Plasma cortisol concentrations increased by 2.6-fold with a mean value of 734±14 nmol/l. Maximal plasma ACTH and β-endorphin concentrations were preceded by discrete secretory bursts with peak amplitudes of 10.5±2.7 and 10.6±2.0 pmol·I−1·min−1 (20-fold and ninefold increases compared to control), respectively. The mass of ACTH released was 114±20 pmol/l (3.4-fold increase), which corresponds to a total amount of 1.25 μg (50% of daily production and 0.5% of reported pituitary stores), assuming a distribution volume of 40 ml/kg. A total amount of 4.4±0.7 mg of cortisol was released after insulin-induced hypoglycemia, based on a mean cortisol secretory mass of 1088±137 nmol/l and a presumed 11.3-1 volume of distribution. Deconvolution-based estimates of the endogenous half-lives of ACTH, β-endorphin and cortisol were 17±0.6, 22±1.7 and 65±5.3 min, respectively. In summary, deconvolution analysis revealed a rapid coordinate activation of ACTH, β-endorphin and cortisol secretion after hypoglycemic stress, which correlated closely but temporally preceded increases in the respective plasma concentrations. Our inference that only a small fraction of pituitary ACTH content is released during hypoglycemic stress emphasizes the large reserve capability of the pituitary corticotropes. The percentage response of adrenal gland to the metabolic stress of hypoglycemia was of lesser magnitude, possibly owing to the rate-limiting properties of cortisol biosynthesis. We conclude that kinetic responses of the hypothalamic—pituitary—adrenal axis to hypoglycemic stress exhibit exquisite temporal synchrony and manifest a marked reserve capacity.
Aldosterone binding to mineralocorticoid receptors of mononuclear leukocytes in diabetic subjects
Authors: Shimada Takeshi , Yasuda Keigo , Mori Akihiro , Ni Huiping , Mercado-Asis Leilani B , Murase Hiroshi , Miura Kiyoshi
Published: June 2009

We present the characteristic features of mineralocorticoid receptor regulation in human mononuclear leukocytes in patients with diabetes mellitus. Eighteen diabetic patients (3M and 15F, aged from 28 to 77 years with a mean of 53±14 (mean±sd) years) and 7 normal subjects (6M and IF, aged from 29 to 59 years with a mean of 41±13 years) were studied. The mean plasma aldosterone concentration in the diabetic patients was significantly lower than that in the normal subjects (137±62 vs 189±36 pmol/l, p<0.05). Seven of the 18 diabetic patients were hypoaldosteronemic. These 7 patients, however, showed normokalemia, except one with mild hyperpotassemia. The number of binding sites of [3H]aldosterone to mineralocorticoid receptor in the diabetic patients was significantly higher than that in the normal subjects (853±281 vs 488±109 sites/cell, p<0.05), but there was no significant difference in Kd of [3H]aldosterone binding to mineralocorticoid receptor between the diabetic patients and normal subjects (1.34±0.37 vs 0.99±0.61 nmol/l). In the diabetic patients, a significant negative correlation was observed (r=0.70, p<0.01) between plasma aldosterone concentration and the binding sites, but not between plasma aldosterone concentration and Kd. In the total subjects, including normal subjects and diabetic patients, a significant negative correlation was also found between plasma aldosterone concentration and binding sites (r=0.72, p<0.001). These results suggest that increased binding sites of mineralocorticoid receptor may help to prevent diabetic patients from being hyperkalemic.
Preliminary evidence for plasma adrenocorticotropin levels as biological correlates of premenstrual symptoms
Authors: Redei Eva , Freeman Ellen W
Published: June 2009

Premenstrual syndrome (PMS) is a menstrual cycle-related disorder of mood and behavior with unknown etiology and lack of evidence of endocrine imbalances. The absence of menstrual cyclicity eliminates PMS symptoms, and cyclic gonadal changes appear necessary but not sufficient cause for behavioral symptoms in predisposed women. As there are many depressive symptoms in PMS, we focused on the neuroendocrine characteristics of depression, primarily hypothalamic—pituitary—-adrenal hyperactivity, and investigated plasma adrenocorticotropin (ACTH) and cortisol levels in the menstrual cycle. Blood samples were drawn daily from ten patients with PMS and eight asymptomatic control subjects who also reported symptoms daily throughout one menstrual cycle. The ACTH levels were significantly lower in patients with PMS compared to control subjects in the luteal phase. Two PMS subgroups were identified by cluster analysis applied to symptom scores. Plasma ACTH levels of PMS Cluster 1 subjects were significantly lower compared to controls. The ACTH levels of PMS Cluster 2 subjects were nearly identical to controls. These preliminary results suggest distinct hormonal subgroups in the heterogeneous PMS population and support further study of ACTH as a biological correlate of PMS.
Ontogenesis of estrogen secretion by porcine fetal testes
Authors: Raeside James I , Wilkinson Chad R , Farkas Gabrielle
Published: June 2009

High levels of estrogen secretion is a characteristic of steroidogenesis in the pig testis in both the adult and newborn male. We have now examined the ability of fetal gonads to secrete estrogens, and compared it with testosterone secretion during prenatal development. Fetuses were recovered from sows (N=33) at 27–114 (term) days of gestation. Gonads were removed for organ culture in TC-199 medium, or used as minced tissues or free cell preparations when taken later in development. Organ cultures were maintained for 96 h with luteinizing hormone added for the last 72 h for one gonad of each pair. Estrone, estradiol-17β and testosterone were measured by radioimmunoassay in media samples. Trace amounts of estrone were detected almost as early as testosterone secretion commenced, but quantities sufficient for confirmation by radioimmunoassay after chromatography were not seen until day 35 of gestation. Estrogen production increased to >0.37 nmol·gonad−1·4 h−1 at term. Testosterone secretion in organ culture was increased by luteinizing hormone but no effect was seen on estrone levels for the first half of pregnancy. Thus, estrogen secretion is a feature of steroidogenesis in the porcine testes even in the early stages of fetal development.
Studies on the action of dexamethasone on prostaglandin production by freshly dispersed amnion cells
Authors: Gibb William , Breton Robert
Published: June 2009

The human amnion may be an important source of prostaglandins (PGs) during pregnancy and possibly labor. Glucocorticoids stimulate PG production in confluent amnion cell cultures, but in freshly dispersed cells they inhibit PG production. The purpose of the present study was to determine if this inhibitory effect occurred at the level of arachidonic acid release from lipids. Cells were labeled with radioactive arachidonate and the release of radioactivity was measured in the presence or absence of dexamethasone. No significant effect of dexamethasone treatment was observed. The possibility that glucocorticoid treatment inhibited the release of arachidonate from a specific species of phospholipid was also examined. However, no difference was found in the distribution of arachidonate between lipids isolated from glucocorticoid-treated and untreated cells. Furthermore, dexamethasone treatment did not alter the lipocortin 1 and 2 content of dispersed cells, determined following sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting. These studies indicate that the inhibition of prostaglandin production by dispersed amnion cells by glucocorticoids most likely occurs at a point distal to arachidonic acid release.
Protein kinase C activation and positive and negative agonist regulation of 3′, 5′-cyclic adenosine monophosphate levels in cultured rat Sertoli cells
Authors: Eikvar Lars , Taskén Kristin Austlid , Eskild Winnie , Hansson Vidar
Published: June 2009

The present study examines the effects of 12-0-tetradecanoylphorbol-13-acetate (TPA) on agonist-regulated 3′, 5′-cyclic adenosine monophosphate (cAMP) formation and cAMP-mediated effects in cultured Sertoli cells from immature rats. Concentration-dependent stimulation of cAMP levels by follicle-stimulating hormone (FSH) was inhibited dramatically by the coaddition of 100 nmol/l TPA, which exerted a similar inhibition of glucagon- and isoproterenol-stimulated cAMP production. These results show that protein kinase C (PKC) activation by TPA attenuates Gs-protein-mediated agonist activation of cAMP production. (− )-N6(R)-Phenylisopropyladenosine (L-PIA), an A1-adenosine receptor agonist, inhibited cAMP stimulation by FSH in a concentration-dependent manner. When LPIA was added in increasing concentrations simultaneously with 100 nmol/l TPA, the L-PIA still inhibited FSH-stimulated cAMP production in a concentration-dependent manner. In the presence of TPA, the half-inhibitory concentration (IC50) for L-PIA inhibition of cAMP formation was reduced by more than one order of magnitude, indicating that PKC activation by TPA increases the sensitivity of Sertoli cells to G-protein-mediated agonist inhibition of cAMP production. The inhibitory effects of TPA on FSH-stimulated cAMP production were still observed when cAMP phosphodiesterase activity was inhibited by 1 mmol/l methylisobutylxanthine or when the activity of Gxi-protein was eliminated by pretreatment with 100 μg/l pertussis toxin. Taken together, the results indicate that PKC activation inhibits agonist-dependent stimulation of cAMP production by phosphorylation of components common to all the activating agonists used, and not via stimulation of Gi-protein activity or degradation of cAMP by cAMP phosphodiesterase activity. The increased sensitivity to L-PIA inhibition of cAMP formation induced by TPA may simply be a result of the reduced activity of the agonist-receptor/Gs-protein/C complex.
Human chorionic gonadotropin binding sites in the human endometrium
Authors: Bhattacharya S , Banerjee J , Sen S , Manna PR
Published: June 2009

The existence of high-affinity and low-capacity specific binding sites for luteinizing hormone (LH)/human chorionic gonadotropin (hCG) has been reported in porcine, rabbit and rat uteri. We have identified hCG binding sites in the human endometrium collected from 35–42-year-old ovulatory and anovulatory women. The binding characteristics of hCG to endometrial tissue preparations from ovulatory and anovulatory women showed saturability with high affinity and low capacity. Scatchard plot analysis showed the dissociation constant of specific binding sites in the ovulatory women to be 3.5 × 10−10 mol/l and in anovulatory women to be 3.1 × 10−10 mol/l. The maximum binding capacity varied considerably between ovulatory (3.85 nmol/kg protein) and anovulatory (6.12 nmol/kg protein) endometrium. Among the divalent metal ions tested (Zn2+, Mg2+, Mn2+, Ca2+—4 mol/l), Zn2+ effected a remarkable increase in [125I]hCG binding to the endometrium (p<0.005) whereas Mn2+ showed a marginal increase and other metal ions did not have any effect. Data obtained with human endometrium indicate an influence of the functional state of the ovary on [125I]hCG binding to endometrium.
Heterologous humoral immune response in patients treated with human growth hormone from different sources
Authors: Cardoso Alicia I , Llera Andrea S , Iacono Rubén F , Domené Horacio M , Martínez Alicia S , Heinrich Juan J , Peña Clara , Poskus Edgardo
Published: June 2009

The existence of homologous anti-human growth hormone (anti-hGH) and heterologous anti-bovine growth hormone (anti-bGH) humoral immune responses in hypopituitary patients under hGH therapy has been reported previously. In order to study the influence of the hormone source, both responses were compared by radiobinding assays performed with [125I]hGH or [125I]bGH as tracers. Fifty-seven hypopituitary patients treated with extractive hGH, recombinant methionyl hGH or authentic recombinant hGH were studied. A very low incidence of heterologous antibodies was found in patients under recombinant hGH therapy, contrary to the high incidence observed in patients treated with extractive hGH preparations. In addition, immunochemical studies performed with a synthetic peptide (hGH 44–128) indicated that this peptide exhibited, in the anti-bGH/[125]bGH radioimmunoassay system, higher reactivity than the native hGH, suggesting that such a fragment resembled an altered conformation of the hormone. The high heterologous response elicited only by the extractive hGH along with the behaviour of the hGH 44–128 fragment supports the fact that the extraction and purification procedures in extractive preparations may alter slightly the structure of the hGH molecule and trigger a heterologous immune response.
Microsomal antibodies during gestation in relation to postpartum thyroid dysfunction and depression
Authors: Pop VJM , de Rooy HAM , Vader HL , van der Heide D , van Son MM , Komproe IH
Published: June 2009

Rationale—Microsomal antibodies have been related to postpartum thyroid dysfunction and postpartum depression. Objectives—To detect the value of microsomal antibodies during gestation in a random population, as a risk factor for thyroid dysfunction and depression during the postpartum period. Main findings—The presence of microsomal antibodies was investigated in a random population of 293 women at 32 weeks' gestation. At the same time, postpartum thyroid function was assessed repeatedly in all women every six weeks up to 34 weeks' postpartum. Postpartum thyroid dysfunction, defined as the presence of abnormal TSH, in combination with abnormal fT4 and/or fT3 values, occurred in 21 women (7.2%) during the postpartum period. Depression was assessed using the Research Diagnostic Criteria without knowing the results of biochemical thyroid function tests. At 32 weeks' gestation there were 27 (9.2%) women with elevated microsomal antibody titres. Compared with microsomalantibody negative women at 32 weeks' gestation, these women had an RR of 20 for developing postpartum thyroid dysfunction and an RR of 1.7 for developing postpartum depression. Conclusions—Women with elevated microsomal antibody titres during gestation are particularly at risk for postpartum thyroid dysfunction, but only have a slightly increased risk for postpartum depression.
Incidence rate and risk factors for thyroid dysfunction during recombinant interleukin-2 therapy in advanced malignancies
Authors: Vialettes Bernard , Guillerand Marie Aude , Viens Patrice , Stoppa Anne-Marie , Baume Daniel , Sauvan Richard , Pasquier Jacques , Marco Marielle San , Olive Daniel , Maraninchi Dominique
Published: June 2009

Immunotherapy using recombinant interleukin 2 (rIL-2) has been shown to induce thyroid dysfunction in some cancer patients. The purpose of the present study was to evaluate the incidence and risk factors of this adverse autoimmune response. Triiodothyronine, thyroxine and thyrotropin levels were measured serially in 146 consecutive patients treated with rIL-2 for refractory solid tumor (77 patients) or malign hemopathy (69 patients); rIL-2 was administered intravenously in 5-day cycles (18 × 106–24 × 106 IU·m−2·day−1) either alone in 79 cases or in combination with autologous bone marrow transplantation in 26 cases, with interferon-γ in 37 cases, with tumor necrosis factor-α in 13 and with cyclophosphamide in five cases. Some patients underwent more than one therapeutic protocol. Peripheral hypothyroidism was present upon entry in nine (6.2%) patients. Thyroid dysfunction appeared or worsened during rIL-2 therapy in 24 (16.4%) patients. Sixteen (10.9%) patients exhibited peripheral hypothyroidism, out of which four exhibited biphasic thyroiditis. Another five (3.4%) patients developed transient hyperthyroidism. Anomaly could not be classified in three patients. Thyroid dysfunction appeared early after one or two cycles. All surviving patients recovered. Only gender and presence of antithyroid antibody were correlated significantly with rIL-2-induced thyroid abnormalities. No correlation was found with any of the other risk factors studied, i.e. type of malignancy, rIL-2 treatment procedure, clinical efficacy, evolution of circulating lymphocyte subsets or other autoimmune antibodies. Antithyroid antibodies were detected in 60.9% of patients with this complication. Thyroid-stimulating antibodies were never detected. In susceptible individuals, rIL-2 can activate autoreactive clones, leading to acute autoimmune thyroiditis similar to postpartum thyroiditis. The high incidence of the complications during this immunotherapy justifies systematic screening.
Histochemical changes in pancreatic islets obtained from obese Zucker rats (fa/fa) on a diabetogenic diet. No evidence for non-enzymatic protein glycation in endocrine cells
Authors: Fürnsinn Clemens , Komjati Martin , Madsen Ole D , Schneider Barbara , Waldhäusl Werner
Published: June 2009

Genetically obese Zucker rats (fa/fa) on a diabetogenic diet rich in lard and sucrose develop chronic hyperglycemia accompanied by severe hyperinsulinemia. Non-enzymatically glycated protein content was increased in tendon (p<0.0001) and aorta (p<0.04), but not nerve, from hyperglycemic rats as compared to normoglycemic lean litter-mates on a conventional chow diet (mmol furosine/mol tyrosine in tissue hydrolysate from 61-week-old rats: tendon, 29.8±1.8 vs 25.9±1.3; aorta, 12.0±1.0 vs 11.0±1.1). In pancreatic islets, non-enzymatically glycated protein was neither found in lean rats of any age nor in the obese up to an age of 36 weeks. At an age of 61 weeks, non-enzymatically glycated protein accumulated in islets of obese animals, resulting in levels of 17.02–44.65 mmol furosine/mol tyrosine. This rise in islet glycated protein content was not accompanied by a comparable increase in plasma glycemia, but simultaneous histological examination of pancreatic tissue revealed fibrosis of islets. Fibers were probably of collagenic quality without islet amyloid polypeptide immunoreactivity. Because collagen is known to be highly susceptible to non-enzymatic glycation, we suspect that collagenic fibers but not endocrine cells are the main source of glycated protein accumulation in these islets. Hence, our data do not give evidence that non-enzymatic protein glycation plays a role in the islet degeneration occurring in hyperglycemia. Furthermore, immunohistochemical staining for various endocrine peptides did not suggest loss of any hormone-producing cell type or defective pancreatic hormone production in hyperglycemic old, obese Zucker rats. The more soluble nature of rat vs human islet amyloid polypeptide may explain the fact that hyperglycemia-induced fibrosis in rat islets does not include amyloidosis, which may contribute to late beta cell failure in human type II diabetes.
Effects of cyclosporin A and verapamil on mouse pancreatic islets
Authors: Shi Chun L , Rooth Pål , Täljedal Inge-Bert
Published: June 2009

Treatment of NMRI mice with cyclosporin A (25 mg/kg body wt) for 11 days caused a marked fall in pancreas insulin content, although plasma glucose and plasma insulin were unchanged. When islets from untreated mice were exposed to cyclosporin A (2 mg/l) in vitro, no effect was seen in the first hour. After 24 h, cyclosporin A had significantly decreased the islet content of insulin. Post-culture microperifusion showed that cyclosporin A for 24 or 72 h inhibited the insulin secretory responsiveness. Verapamil in vivo (0.4 mg/kg body wt per day) or in vitro (37.5 μg/l) did not modify these effects. Verapamil at 25 mg/l suppressed the release of insulin but afforded no obvious protection against cyclosporin A during culture. The beneficial action of verapamil on islets transplanted to the kidney may reflect renal events rather than a primary interaction of drugs in the islets.
Effect of exogenous hydrogen peroxide on iodide transport and iodine organification in FRTL-5 rat thyroid cells
Authors: Chen Ge , Pekary A Eugene , Sugawara Masahiro , Hershman Jerome M
Published: June 2009

Hydrogen peroxide plays an important role in the regulation of iodination and thyroid hormone formation. In the present study, the effect of exogenous H2O2 on 125I transport and organification was investigated in FRTL-5 rat thyroid cells. Less than 20 passages after subcloning, cells in 24-well plates (6 × 104 cells/well) were maintained in a thyrotropin (TSH)-containing medium (6H) for 3 days. A TSH-free medium (5H) was then used for the next 7 days. A 1-h exposure to H2O2 stimulated 125I transport and 125I organification at 0.1–0.5 mmol/l H2O2 and had a toxic effect on FRTL-5 cells at 5 mmol/l. Hydrogen peroxide (0.5 mmol/l) augmented the iodide transport and iodine organification induced by TSH (333U/l) by two- and threefold, respectively. The biphasic effect of H2O2 was blocked totally by 5–200 μg/l of catalase. Catalase by itself did not influence TSH-mediated 125I transport and 125I organification. Hydrogen peroxide (0.5 mmol/l) added to cells in 5H medium increased Na+K+-ATPase activity twofold. Ouabain (1 mmol/l), an inhibitor of Na+K +-ATPase, completely inhibited the twofold increase in 125I transport induced by 0.5 mmol/l H2O2 but only inhibited H2O2-induced 125I organification by 28%. Methimazole (1 mmol/l), an inhibitor of thyroid peroxidase, had no effect on H2O2-mediated 125I transport but totally blocked the fivefold rise in 125I organification induced by 0.5 mmol/1 H2O2. The effect of H2O2 on intracellular cyclic adenosine monophosphate (cAMP) levels also was studied. Hydrogen peroxide (0.5 mmol/l) decreased baseline and 160 mU/l TSH-induced cAMP levels by 35 and 87%, respectively, while a 3-h incubation with 0.5 mmol/l H2O2 increased Na + K +-ATPase in 5H and 6H media. We conclude that H2O2 plays an important role in the regulation of iodide transport and organification and also may affect signal transduction and the electrochemical gradient in thyroid cells. Our results also provide evidence that functional thyroid peroxidase activity is present in FRTL-5 cells.
Effects of endurance training on hormonal responses to prolonged physical exercise in males
Authors: Vasankari Tommi J , Kujala Urho M , Heinonen Olli J , Huhtaniemi Ilpo T
Published: June 2009

The effect of several years' endurance training on hormonal changes during acute prolonged physical exercise was studied. In trial I, 13 cross-country skiers were studied before and after a 75-km ski race and 3 weeks later on a control day. In trial II, 10 trained and 8 untrained subjects bicycled for 4 h on the road with as high a performance level as possible. Venous blood samples were taken in both trials before and after the exercise. In trial I, serum concentrations of luteinizing hormone (p<0.01) and follicle-stimulating hormone (FSH, p <0.001) decreased more from morning to afternoon samples, and cortisol (p <0.001) and growth hormone (GH, p <0.001) increased more during the ski race when compared to the control day. Serum testosterone decreased during the ski race (p <0.01) but not on the control day. In trial II, a group difference was seen in serum FSH levels which was higher in the trained than untrained subjects at all three time points (F =4.66, p=0.046). A significant trial-group interaction (p =0.020) was seen in GH, the GH being lower before exercise and higher 2 h after exercise in the untrained subjects. There was a significant group contrast between pre- and post-exercise samples in testosterone (p = 0.021) and cortisol (p = 0.022). In conclusion, the higher basal FSH concentration in the trained versus untrained subjects may be a sign of compensated hypogonadism due to intensive chronic training or it may be due to dysfunction of Sertoli cells. Signs of adaptation to resist the hormonal changes caused by acute physical exercise can be seen in the trained subjects when compared to the untrained subjects.
Plasma endothelin-1 and big endothelin-1 levels in women with pre-eclampsia
Authors: Sudo Norihito , Kamoi Kyuzi , Ishibashi Miyuki , Yamaji Tohru
Published: June 2009

To examine a possible role for endothelin-1 (ET-1) and conversion of big ET-1 to ET-1 in the pathophysiology of pre-eclampsia, we measured plasma levels of ET-1 and big ET-1 in 16 women with pre-eclampsia in the third trimester and compared them with those in 11 age-matched normotensive pregnant women and in 10 age-matched pregnant women with chronic hypertension in the third trimester. The plasma concentrations of ET-1 and big ET-1 in the normotensive pregnant women were significantly lower than those in 16 non-pregnant women with a higher molar ratio of big ET-1 to ET-1 in the former group. The plasma concentrations of ET-1 and big ET-1 in the women with pre-eclampsia, on the other hand, were significantly higher than those in the normotensive pregnant women and the molar ratio of big ET-1 to ET-1 in the former group was less than that in the latter group. In sharp contrast, plasma ET-1 and big ET-1 levels in the pregnant women with chronic hypertension were not significantly different from those in the normotensive pregnant women. When examined after delivery, elevated plasma ET-1 and big ET-1 in the women with pre-eclampsia declined, with restoration of normal blood pressure, to the levels in the normotensive women after parturition. There were no significant differences of the levels of ET-1 and big ET-1 in umbilical venous plasma and simultaneously drawn maternal plasma at cesarean section between normotensive pregnant women and women with pre-eclampsia, respectively. These results suggest that normal pregnancy is associated with decreased plasma concentrations of ET-1 with reduced conversion of big ET-1 to ET-1 in maternal vascular endothelial cells, and the derangement of this regulatory system plays an important role in the pathophysiology of pre-eclampsia.
Relationship between ovarian steroids, gonadotrophins and relaxin during the menstrual cycle
Authors: Johnson MR , Carter G , Grint C , Lightman SL
Published: June 2009

The circulating levels of relaxin have been measured and their relationship with the plasma levels of oestradiol (E2), progesterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) have been investigated during the normal menstrual cycle. In addition, the effect of human chorionic gonadotrophin (hCG) on plasma relaxin levels has been studied. In the first part of the study, blood samples were obtained on days 5, 10 and 15 of the follicular phase and on alternate days from the day of the LH surge (detected in early-morning urine and confirmed by circulating levels of LH) until day 6 of the following follicular phase in nine normally cycling female volunteers. In the second part of the study, a single intramuscular dose of hCG (10 000 IU) was given on day 11 of the menstrual cycle. Relaxin was detectable from the mid-luteal phase until the onset of menstruation. The plasma levels of relaxin on days 10 and 12 of the luteal phase were significantly greater than on day 6. Positive associations between the circulating levels of relaxin and E2 and negative associations between the plasma levels of FSH and those of both relaxin and E2 were found on days 8, 10 and 12 of the luteal phase. The relationship between E2 and FSH was stronger than that between relaxin and FSH. Exogenous hCG had no effect on plasma relaxin levels. The pattern of the relationship between E2 and relaxin suggests that a common mechanism may regulate their release or that plasma relaxin levels are determined by those of E2. Furthermore, the absence of any relationship between endogenous LH levels and those of relaxin and the lack of effect of exogenous hCG on plasma relaxin levels suggest that LH does not influence the circulating levels of relaxin directly. The negative relationship between FSH and relaxin is probably indirect, mediated by E2, although it is possible that relaxin influences FSH release directly.
Differences in serum lipids, lipoproteins, sex hormone binding globulin and testosterone between the follicular and the luteal phase of the menstrual cycle
Authors: Schijf Charles PT , van der Mooren Marius J , Doesburg Wim H , Thomas Chris MG , Rolland Rune
Published: June 2009

Fifty-four healthy women were studied during the follicular and the luteal phase of one menstrual cycle to determine possible cyclic influences on several parameters. After a 12-h overnight fast, blood samples were obtained between 08.00 h and 09.30 h and processed for total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoproteins A-I and B and total triglycerides. In the same samples we also measured serum concentrations of follicle-stimulating hormone, luteinizing hormone, 17β-oestradiol, progesterone, sex hormone binding globulin and testosterone. Serum total cholesterol, low-density lipoprotein cholesterol and the related apolipoprotein B were decreased significantly with 0.35 mmol/l, 0.44 mmol/l and 15 mg/l, respectively, during the luteal phase as compared to the follicular phase (p≤0.01). The ratios of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol and of total cholesterol/high-density lipoprotein cholesterol were also significantly lower (p <0.01) in the luteal phase because high-density lipoprotein cholesterol and its major carrier apolipoprotein A-I as well as serum triglycerides remained unchanged in the two cycle phases compared. Sex hormone binding globulin was significantly higher (p <0.001) in the luteal phase than in the follicular phase of the investigated cycles, whereas serum testosterone remained unchanged in the two cycle phases compared. Therefore, the free androgen index decreased in the luteal phase (p<0.01). These results indicate the necessity to define the cycle phase in which blood has been collected during control cycles in studies concentrating on possible effects of oral contraceptives or other administered sex steroids on serum lipids, lipoproteins and androgen metabolism. Further, we suggest that variations in the serum concentrations of lipids and lipoproteins during the normal menstrual cycle should be considered when normal range values are defined.
Infant feeding, fetal growth and adult thyroid function
Authors: Phillips David IW , Barker David JP , Osmond Clive
Published: June 2009

Prolonged breast-feeding in humans is associated with increased low-density lipoprotein cholesterol and higher death rates from ischaemic heart disease in adult life. The reasons for this link are unclear. A possible explanation is that thyroid hormones present in breast milk and absorbed by the suckling infant could, by the process of hormonal imprinting, permanently down-regulate the set point of thyroid homeostasis. Thyroid hormones influence cholesterol metabolism, and could explain the link between infant feeding and the regulation of cholesterol levels in the adult. We therefore investigated whether infant feeding was related to adult thyroid function in 303 women aged 60–71 years who were born in the county of Hertfordshire, UK, where birthweight, the weight at 1 year and the method of infant feeding had been recorded routinely. Free thyroxine (FT4) concentrations but not free triiodothyronine (FT3) or thyrotrophin (TSH) were increased in the women who, as infants, had been breast-fed beyond 1 year of age (p <0.01). In women who were bottle-fed, with or without breast-feeding, serum TSH rose and FT4 fell with increasing birthweight (p=0.01 and p=0.04, respectively). Although the metabolic significance of these findings is unclear, they suggest that the set point of thyroid function in the adult is determined by fetal growth and infant feeding.
Thyroxine administration to infants of less than 30 weeks' gestational age does not increase plasma triiodothyronine concentrations
Authors: van Wassenaer Aleid G , Kok Joke H , Endert Erik , Vulsma Thomas , de Vijlder Jan JM
Published: June 2009

Very preterm infants (less than 30 weeks' gestational age) were treated with thyroxine in three different dosage schemes: 10, 8 and 6 μg·kg−1 birthweight·day−1 during the first 6 weeks of life. The aim was to prevent transient hypothyroxinemia of the preterm infant. Plasma levels of thyroxine, free thyroxine, triiodothyronine, reverse triiodothyronine, thyroxine-binding globulin and thyrotropin were measured weekly. Thyroxine administration increased thyroxine and free thyroxine levels most properly in the 8-μg supplementation group. It did not result in a change in plasma triiodothyronine levels. Levels of reverse triiodothyronine increased in relation to the thyroxine dosage. Thyrotropin secretion was suppressed in the 6- and 8-μg groups during the first 2 weeks, while in the 10-μg group suppression lasted 4 weeks. No clinical adverse effects of thyroxine administration were seen. We conclude that 8 μg thyroxine·kg−1 birthweight·day−1 for 6 weeks prevents transient hypothyroxinemia. The finding that plasma triiodothyronine concentrations are not influenced by thyroxine administration suggests a specific maturation process in the deiodination of thyroxine.