bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibodies to 'second colloid antigen'. A study on the prevalence in sporadic forms of congenital hypothyroidism
Authors: van Trotsenburg Paul , Vulsma Thomas , Bloot André M. , Van der Gaag Reindert D. , Lens Jan Willem , Drexhage Hemmo A. , de Vijlder JanJ.
Published: December 2008

Antibodies against the so called 'second colloid antigen' (CA2 antibodies) occurred in 51% of the mothers of hypothyroid children detected by screening for neonatal congenital hypothyroidism in Quebec (N = 49) and in The Netherlands (N = 26). In The Netherlands where corresponding neonatal serum was available, 31% (8 of 26) of the infants with congenital hypothyroidism were positive for antibodies against the second colloid antigen. When during follow-up, 3 to 5 years after diagnosis, the mothers and their children were investigated, 46% (7 of 15) of the mothers were positive for antibodies against the second colloid antigen, whereas 29% (4 of 14) of the hypothyroid children were also positive. Various control groups did not show more than a 12% positivity. This presence of thyroid-reactive antibodies in a proportion of the hypothyroid children 3 to 5 years after diagnosis is not compatible with a mere transplacental passage; it indicates that the antibodies must be produced by the mothers and by the children themselves. We conclude that a thyroid autoimmune response occurs in a considerable part of infants with congenital hypothyroidism and their mothers and that this immune response seems to persist in both of them for years.
Lys- and Tyr-arylamidase activities in serum and brain during the estrous cycle of the rat
Authors: de Gandarias J. M. , Casis L. , Irazusta J. , Echevarría E. , Arechaga G. , Ramírez M.
Published: December 2008

Peptidase enzymes are involved in neuropeptide processing or degradation. In order to analyse a possible functional participation of these enzymes, arylamidase activity of several rat brain regions and serum was assayed in the soluble fraction during the estrous cycle using L-Lys- and L-Tyr-β-naphthylamide as substrates. Significant differences were present in the hypothalamus, the pituitary and serum when both substrates were used. However, there were no differences in cortical areas. These results suggest a role for arylamidase activity in the hormonal changes that happen during the estrous cycle of the rat.
Human interleukin 1β stimulates islet insulin release by a mechanism not dependent on changes in phospholipase C and protein kinase C activities or Ca2+ handling
Authors: Welsh Nils , Nilsson Thomas , Hallberg Anders , Arkhammar Per , Berggren Per-Olof , Sandler Stellan
Published: December 2008

Isolated islets from adult rats or obese hyperglycemic (ob/ob) mice were incubated with human recombinant interleukin 1β in order to study whether the acute effects of the cytokine on islet insulin release are associated with changes in islet phospholipase C activity, Ca2+ handling or protein phosphorylation. The cytokine stimulated insulin release both at low and high glucose concentrations during one hour incubations. In shortterm incubations (<1 min) interleukin 1β did not affect the production of inositoltrisphosphate. Addition of interleukin 1β affected neither the cytoplasmic free Ca2+ concentration at rest nor that observed subsequent to stimulation with a high concentration of glucose. Furthermore, the endogenous protein kinase C activity, as visualized by immunoprecipitation of a 32P-labelled substrate for this enzyme, was not altered by interleukin 1β. Separation of 32P-labelled proteins by means of 2-dimensional gel electrophoresis failed to reveal any specific effects of the cytokine on the total protein phosphorylation activity. These results suggest that the stimulatory effects on insulin release exerted by interleukin 1β are not caused by acute activation of phospholipase C and protein kinase C or by an alteration of islet Ca2+ handling of the B-cells.
Pituitary-testicular axis in obese men during short-term fasting
Authors: Röjdmark Sven , Asplund Anette , Rössner Stephan
Published: December 2008

To investigate whether short-term fasting affects the pituitary-testicular axis in obese subjects, 9 massively obese men (Body Mass Index 39.0 ± 1.3, mean± sem) were given two identical iv GnRH tests, the first (control) after an overnight fast, the second after 56 h of food deprivation. Short-term fasting augmented the GnRH-induced LH incremental area by 26%(1317±251 vs 1661 ± 297 U · 1−1 · min−1, p <0.05), but failed to affect the corresponding testosterone incremental area. Eight non-obese normal men (Body Mass Index 22.2 ± 0.5) were investigated for comparison. All of them were studied according to the same protocol as the obese group. Short-term fasting increased the GnRH-elicited LH response by 67% in the non-obese group (LH incremental areas 2147 ± 304 vs 3581 ± 256, p <0.01), and the corresponding testosterone response by 180% (testosterone incremental areas 111 ±61 vs 311±49 μg · 1−1 · min−1, p <0.01). These results imply that food deprivation affects the pituitary-testicular axis differently in obese and non-obese men.
Sequential immunohistochemical expression of IGF-I and the transferrin receptor in regenerating rat muscle in vivo
Authors: Jennische Eva
Published: December 2008

The immunohistochemical expression of insulin-like growth factor I and the transferrin receptor was investigated in regenerating rat skeletal muscle. Muscle injury was induced in the extensor digitorum longus muscle in one hind limb by tourniquet ischemia. The regenerating muscles were investigated 3 to 7 days after the injury. Expression of IGF-I and the transferrin receptor was demonstrated in cryostat sections by a doublestaining method. It was found that both markers were transiently expressed by the regenerating muscle cells. Expression of IGF-I immunoreactivity preceded that of the transferrin receptor and the staining for IGF-I disappeared 1 to 2 days before the staining for the transferrin receptor. The data are compatible with a regulatory role of IGF-I on the transferrin receptor.
Changes of serum thyroid hormone levels induce malformations on early embryogenesis in rats
Authors: Harakawa Seijiro , Akazawa Shoichi , Akazawa Mihoko , Hashimoto Masumi , Yamashita Shunichi , Izumi Motomori , Nagataki Shigenobu
Published: December 2008

The incidence of malformation is increased in infants of hyperthyroid or hypothyroid woman. Although many papers reported that the fetus is insulted from maternal thyroid hormone, the placenta (maternalfetal barrier) is not yet fully developed before 11.5 days of gestation in rat embryos, suggesting the effect of thyroid hormone on early rat embryogenesis. This study was, therefore, undertaken to investigate whether excess or lack of thyroid hormones would affect early embryogenesis in rat embryo culture. Malformations including open neuropore and microencephaly were observed in 10 of 30 embryos incubated in hyperthyroid serum, and in 12 of 42 cultured in T3-enriched normal serum. Similar malformations were observed in 14 of 42 embryos cultured in hypothyroid serum and in 10 of 30 cultured in hypothyroid serum supplemented with T3. The frequencies of these malformations were significantly higher than in the control embryos (0 in 72 embryos) cultured with normal rat serum. These results suggest that the maternal thyroid status might play an important role for the complication of fetal malformations during early gestational period.
Insulin-like growth factors I and II in healthy man.
Authors: Guler Hans-Peter , Zapf Jürgen , Schmid Christoph , Froesch E. Rudolf
Published: December 2008

IGF-I and -II share specific serum carrier proteins which elute on neutral Sephadex G-200 gel permeation chromatography at apparent molecular masses of 50 and 200 kD. The half-lives of free and carrier protein-bound 125I-IGF-I and -II were determined after bolus injections of the tracers into two normal adults. Labelled IGF-I and -II migrated first with the 50-kD and later with the 200-kD complex. In these complexes their apparent half-lives were 20–30 min and 12–15 h, respectively. The apparent half-life of free 125I-IGF-I and -II was 10–12 min. In a second set of experiments, recombinant human insulin-like growth factor I was infused during 6 days in two healthy adults at a dose of 20 μg · kg−1 · h−1 (corresponding to around 30 mg/day). Serum obtained before and during the infusion was subjected to neutral Sephadex G-200 gel permeation chromatography and fractions were pooled according to the apparent molecular masses at which the carrier protein complexes elute. IGF-I and -II in these pools were determined by RIA. Before the IGF-I infusion, 92 and 272 μg/l of IGF-I and -II were found in the 200-kD complex, 45 and 91 μg/l in the 50-kD complex, and 15 and 5 μg/l were present in the free form. Corresponding figures during the IGF-I infusion were 389 and 18 μg/l for the 200-Kd complex, 201 and 54 μg/l for the 50-kD complex, and 80 and < 1 μg/l for free IGF-I and -II. Using the half-lives of the tracer studies and the levels of the different molecular weight forms of IGF in serum, the production rates for IGF-I and -II were calculated to be 10 mg and 13 mg per day.
Regulation of amino acid transport in rat and human thyroid cells
Authors: Rotella C. M. , Piani F. , Frediani U. , Toccafondi R.
Published: December 2008

To clarify the role of insulin, IGF-I and TSH in thyroid cell regulation, their effects on amino acid transport were studied separately. These effects were noted and compared using both the Wistar rat thyroid cell line and human thyroid cell cultures. Insulin, IGF-I and TSH were able independently to induce the radiolabelled α-aminoisobutyric acid transport within the rat thyroid cells: TSH stimulated the amino acid transport in rat thyroid cells in a dose-dependent way from 1 pmol/l to 10 nmol/l. Similarly, insulin increased amino acid transport significantly from 0.17 nmol/1 up to 0.17 μmol/l and IGF-I from 0.13 pmol/l up to 0.13 μmol/l. The combined effects of insulin and TSH on amino acid transport were equal to the theoretical sum of the activities, whereas those of IGF-I and TSH were greater than the theoretical one. When human thyroid cell cultures were used, a significant increase of labelled amino acid transport was induced by TSH, i.e. from 0.1 pmol/l to 10 pmol/l; IGF-I stimulated amino acid transport in a range from 0.13 pmol/l to 13 pmol/l, under the same conditions. Conversely, only large doses of insulin, i.e. 1.7 nmol/l, were able weakly to stimulate amino acid transport. When submaximal TSH and IGF-I doses were co-incubated in human thyroid cells, an additive effect on amino acid transport was observed.
The role of catecholamines in estradiol and progesterone secretion by cultured explants and cells of human term placentae
Authors: Barnea Eytan R. , Perlman Rina , Fakih Hassan , Bick Tova , Kol Shahar , Hochberg Zeev
Published: December 2008

The effects of physiological concentrations of the native catecholamines norepinephrine and epinephrine upon term placental hormonal function were examined by measuring estradiol and progesterone secretion by organ and cell culture systems. Results show that, in explants, both catecholamines caused a significant increase in the secretion of both sex steroids, p < 0.05. Estradiol secretion was blocked by the alpha and beta adrenergic receptors antagonists, phenoxybenzamine and propranolol, respectively, p < 0.05. Norepinephrine but not epinephrine dependent progesterone secretion was blocked by propranolol. In cells, epinephrine stimulated cyclic AMP generation and caused a 30% increase in estradiol secretion, p < 0.05. Both were abrogated by propranolol. Norepinephrine increased secretion by 25%, p < 0.05. This was inhibited by yohimbin and prazosin, alpha-1 and -2 receptors antagonists, respectively. In conclusion, the placenta in vitro is a target organ for catecholamines. The marked response of the explant system as compared with the marginal response of the cell culture system indicates that cell to cell contact/communication is required for full expression of catecholamine effect.
Effect of gonadectomy on growth hormone, IGF-I and sex steroids in children with complete and incomplete androgen insensitivity
Authors: Cicognani Alessandro , Cacciari Emanuele , Tacconi Moreno , Pascucci Maria G. , Tonioli Susanna , Pirazzoli Piero , Balsamo Antonio
Published: December 2008

IGF-I, testosterone and estradiol levels were evaluated in 8 girls with androgen insensitivity immediately before and from 1 to 3 months after bilateral gonadectomy. In 6 patients GH secretion was evaluated before and after gonadectomy by means of an arginine test and in 3 a sleep test was also performed. Mean IGF-I level before surgery was significantly higher than that of normal controls (2850 ± 1230 vs 1680 ± 1040 U/l, p < 0.025). After gonadectomy a significant decrease was evident for testosterone, estradiol and IGF-I levels. A positive correlation between IGF-I and estradiol levels was present before surgery (p < 0.005). The presence of a correlation with estradiol, but not with testosterone, and the knowledge that this syndrome is due to an insensitivity to androgens, but not to estradiol, support the hypothesis that the estradiol level is the major determinant for the control of IGF-I values in these patients. After gonadectomy, a substantial decrease of the 12-h nocturnal GH secretion was evident. Comparison of the nocturnal GH levels before surgery of the 3 patients with those of normal subjects of the same age showed hormonal values higher than 1 sd over the mean values of control subjects. Even if the number of patients studied is too small to draw any definitive conclusion, these data may suggest that sex hormones play a role in the control of IGF-I levels, a function which seems to be mediated through GH secretion.
Changes of blood flow in the adenohypophysis of normal and estrogen pretreated Fisher rats by tamoxifen
Authors: Stawowy Andrzej , Kemeny Andras A. , Jakubowski Jan
Published: December 2008

Blood flow was measured in the adenohypophysis and in the cerebral cortex of female F344 rats over a period of 90 min using the hydrogen clearance method. Tamoxifen, 1 mg/kg, administered iv reduced the blood flow in the adenohypophysis by 35%, whereas cerebral blood flow and arterial pressure remained unchanged. Seven days sc treatment with tamoxifen (1 mg/kg daily) had no demonstrable effect on blood flow. Anterior pituitary hyperplasia was induced in 15 rats with diethylstilbestrol containing implants. These rats responded to 7 days of sc tamoxifen treatment by 30% increase in adenohypophyseal blood flow. These results suggest that tamoxifen has a different effect on adenohypophysial circulation of the rat depending on whether it is administered in a low- or high-estrogen state.
Controlled release of a GnRH agonist from a polyhydroxybutyric acid implant: reversible suppression of the menstrual cycle in the macaque
Authors: Fraser H. M , Sandow J. , Seidel H. R. , Lunn S. F.
Published: December 2008

The use of polyhydroxybutyric acid as a matrix for delivery of the GnRH agonist buserelin was studied in adult stumptailed macaques with regular menstrual cycles. This material contained 5.0 mg buserelin in a disk of 0.6 cm diameter and 0.15 cm thickness. The effects on pituitary-ovarian function were examined and buserelin release profiles from 30000 and 150000 molecular weight polyhydroxybutyric acid matrices were compared. In an attempt to reduce the high initial release rate of buserelin from these disks, and to prolong the effective period of release, implants of 30 000 molecular weight were coated with cyanoacrylate. The implants were removed after 28, 35 or 42 days for the 30000, the 150000 and the coated implants, respectively. The urinary excretion profile for the agonist revealed a high initial release of buserelin from these implants followed by a rapid decline. The coated disks released significantly less (p < 0.05) buserelin over the first 3 days than did either of the uncoated implants, but maintained release of the agonist over a longer period. Inhibition of ovulation and suppression of estradiol secretion lasted for the duration of treatment in 3 of 5 macaques receiving the 30000 implant, and in 5 of 5 receiving the 150000 or the coated implant. In 3 macaques in whom the coated implant was left in situ, ovulation was suppressed for 104 ± 3.7 days. These results demonstrate that a polyhydroxybutyric acid matrix can be used as a depot formulation for a GnRH agonist and that improved control of release of the agonist can be achieved by coating such implants with cyanoacrylate. This approach may be useful in experimental and clinical situations and may be applicable for delivery of other peptide hormones.
Azathioprine in the treatment of thyroid-associated ophthalmopathy
Authors: Perros Petros , Weightman David R. , Crombie Alex L. , Kendall-Taylor Pat
Published: December 2008

Azathioprine is used in the treatment of thyroid-associated ophthalmopathy, but its effectiveness has not been evaluated. In the present study 20 patients with moderately severe ophthalmopathy were recruited; 10 patients received azathioprine and the other 10 matched patients served as controls. During the treatment period (lasting 1 year) and 1 year later, no changes were detected in exophthalmometer readings, visual acuity or measurement of palpebral aperture. Differential intraocular pressure fell with time in both groups. Azathioprine treatment did not significantly influence these parameters, although it did induce significant decrease in thyroid microsomal antibodies and in thyroid-stimulating hormone binding inhibiting immunoglobulin index. The study demonstrates that thyroid-associated ophthalmopathy of moderate severity, often improves with time without treatment. Azathioprine is not an effective treatment for patients with moderately severe thyroid-associated ophthalmopathy. The study emphasises the necessity for an adequately matched control population in the evaluation of therapy.
Triiodothyronine autoantibodies in Graves' disease: Their changes after antithyroid therapy and relationship with the thyroglobulin antibodies
Authors: Wang Pei-Wen , Huang Miau-Ju , Liu Rue-Tsuan , Chen Chung Dar
Published: December 2008

Sera of 63 patients with Graves' disease, and 49 control subjects were assayed for T3 autoantibodies by a sensitive radioimmunoassay after being stripped of the endogenous thyroid hormone. T3 autoantibodies were demonstrated in 27% of patients with Graves' disease. After antithyroid treatment, T3 autoantibodies in 75% of the patients with positive antibody before therapy changed to negative titre during a follow-up period of 1 to 12 months. Also, a significant decrease of T3 autoantibodies was observed at 1 month after therapy in all patients who received antithyroid treatment. A further study of T3 autoantibodies and anti-thyroglobulin antibodies showed that the latter were demonstrated in 100% of patients with positive T3 autoantibodies and that T3 autoantibodies existed in about one third of patients with positive anti-thyroglobulin antibodies. The results suggested that T3 autoantibodies could be a subpopulation of the heterogenous anti-thyroglobulin antibodies. Although the fall of T3 autoantibodies in some patients was correlated to that of anti-thyroglobulin antibodies, the overall correlation between T3 autoantibodies and anti-thyroglobulin antibodies was poor. In conclusion: 1. T3 autoantibodies may be suppressed by antithyroid drugs. 2. Being a subpopulation of anti-thyroglobulin antibodies, T3 autoantibodies may be caused by an antigenic site within the big thyroglobulin molecule, whereas their titre was not correlated with that of the overall heterogenous anti-thyroglobulin antibodies.
Effects of central osmotic stimulation on vasopressin and enkephalin release into the blood and cerebrospinal fluid and blood pressure
Authors: Ota Kozo , Kimura Tokihisa , Matsui Kuniaki , Iitake Kazuhiro , Shoji Masaru , Inoue Minoru , Sato Kazutoshi , Ohta Masahiro , Yamamoto Tadasu , Yoshinaga Kaoru
Published: December 2008

To assess the central effect of hypertonic NaCl on the release of vasopressin (AVP) and methionine enkephalin-like substances into the blood and cerebrospinal fluid, and on blood pressure, ventriculocisternal perfusion (0.25 ml/min, 60 min) was performed in anesthetized dogs with artificial cerebrospinal fluid (CSF), either isotonic (300 mosmol/kg) or hypertonic (600 and 1200 mosmol/kg). The effect of central administration of a V1-AVP antagonist on the central osmotic challenge was also studied. In dogs, given 600 mosmol/kg, CSF osmolality increased with a concomitant rise in mean arterial pressure and plasma AVP concentrations. Plasma osmolality, heart rate, CSF AVP and plasma and CSF methionine enkephalin-like substances showed no significant change. In dogs, given 1200 mosmol/kg, the CSF osmolality increase was accompanied by a rise in mean arterial pressure, heart rate, plasma AVP and CSF AVP. Plasma osmolality and plasma and CSF methionine-enkephalinlike substances did not change significantly. A V1-AVP antagonist given centrally attenuated the rise in mean arterial pressure induced by osmotic challenge. In dogs, given 300 mosmol/kg, no parameters changed significantly except for a gradual fall in heart rate. These results suggest that central osmotic stimulation by hypertonic NaCl increases blood pressure, heart rate and the release of AVP, but not methionine enkepholin-like substances, into the blood and CSF, and a V1-blocker given centrally attenuates the pressor response.
Evaluation of the pituitary-adrenal axis before, during and after pituitary adenomectomy. Is perioperative glucocorticoid therapy necessary?
Authors: García-Luna Pedro P. , Leal-Cerro Alfonso , Rocha José L. , Trujillo Francisco , Garcia-Pesquera Felipe , Astorga Ricardo
Published: December 2008

Under the supposition that ACTH secretion will be compromised by surgical trauma, patients with pituitary adenomas undergoing transsphenoidal adenomectomy are frequently given corticoids, even though this therapy is controversial. We studied 10 patients with pituitary adenomas whose adrenocortical function was sufficient prior to surgery. The ACTH and cortisol levels rose significantly during surgery in all of these patients. Five patients completed a two-year postoperative follow-up period and their ACTH and cortisol values remained within normal limits. It may be that patients undergoing transsphenoidal surgery for pituitary adenomas do not need perioperative glucocorticoid treatment, since the hypophyseal-adrenal axis does retain its integrity.
A polyclonal antiserum against chromogranin A and B - a new sensitive marker for neuroendocrine tumours
Authors: Eriksson B. , Arnberg H. , Öberg K. , Hellman U. , Lundqvist G. , Wernstedt C. , Wilander E.
Published: December 2008

Chromogranins A, B, and C, proteins that are co-stored and co-released with peptides and amines, have been identified in a variety of neuroendocrine tissues, both normal and neoplastic. We examined the secretion of chromogranin A and chromogranin A + B by hormone-producing tumours in patients with endocrine pancreatic tumours, carcinoid tumours, pheochromocytomas, and small cell lung cancer. The radioimmunoassay determining the plasma concentrations of chromogranin A + B showed a greater sensitivity than that determining chromogranin A alone. All patients with endocrine pancreatic tumours, carcinoids, and pheochromocytomas had increased levels of chromograin A + B, whereas a small number of the patients (5/18 with endocrine pancreatic tumours and ⅓ with pheochromocytomas) had normal levels of chromogranin A. Also in immunocytochemical stainings, our polyclonal antiserum detecting both chromogranin A and B showed a greater sensitivity than other available antisera against chromogranin A, B and C. We have demonstrated that a polyclonal antiserum against a mixture of chromogranin A and B might be a more sensitive marker than chromogranin A alone for diagnosing neuroendocrine tumours. This is not surprising, since both chromogranins are widely distributed in neuroendocrine cells.
Metabolic fuel and amino acid transport into the brain in experimental hypothyroidism
Authors: Mooradian Arshag D.
Published: December 2008

The effect of hypothyroidism in the adult rat on blood-brain barrier and muscle transport of hexoses, neutral amino acids, basic amino acids, monocarboxylic acids, and ketone bodies was examined using single arterial injection-tissue sampling technique. The cerebral blood flow and brain extraction of 3H2O (internal reference substance) was not altered in 3-month-old hypothyroid rats maintained on methimazole, 0.025% in the drinking water, for 7 weeks. The brain uptake index of D-β-hydroxybutyrate was significantly reduced in hypothyroid rats (2.4 ± 0.3 vs 4.6 ± 0.6% p<0.001). Hypothyroid rats given thyroid hormone replacement therapy had normal brain uptake of D-β-hydroxybutyrate (4.4 ± 0.8%). The brain uptake index of butyrate was also significantly reduced in hypothyroid rats (39.3 ± 2.1 vs 47.2 ± 0.74%, p<0.001). The brain uptake index of other test substances and muscle uptake of nutrients examined were not altered in hypothyroid rats. These studies indicate that of the four transport systems examined in two tissues, the blood-brain barrier monocarboxylic acid transport system is most susceptible to the hypothyroidism-induced changes.
Interleukin 6 possibly induced by interleukin 1β in the pituitary gland stimulates the release of gonadotropins and prolactin
Authors: Yamaguchi Masaaki , Matsuzaki Noboru , Hirota Kenji , Miyake Akira , Tanizawa Osamu
Published: December 2008

The abilities of recombinant human interleukin 1 (IL-1) and IL-6 to induce release of FSH, LH and PRL from rat pituitary cells in vitro were examined. IL-1 and IL-6 induced significant releases of FSH, LH and PRL within 3 h. The extents of release of these compounds induced by IL-1 and IL-6 were similar to those induced by GnRH and TRH. Rat anterior pituitary cells released IL-6 spontaneously, and its release was enhanced by IL-1β. This effect of IL-1β was inhibited significantly by a rabbit anti-IL-1β antiserum. These findings suggest that IL-1 induced the release of IL-6 from rat pituitary, and that the released IL-6 stimulated the secretions of FSH, LH and PRL.
Effects of parathyroid hormone fragments on the growth of murine mandibular condylar cartilage in vitro
Authors: Shurtz-Swirski Revital , Lewinson Dina , Shenzer Pesia , Mayer Hubert , Silbermann Michael
Published: December 2008

The present study showed that the fragment hPTH (1–34) is mitogenic in organ cultures of neonatal mandibular condylar cartilage, and even more so in late fetal condyles. Three fragments of hPTH were used to clarify which part of the molecule possesses a mitogenic effect alike that of the native hormone: hPTH (1–34), (28–48) and (53–84). [3H]thymidine incorporation into trichloracetic acid insoluble material and quantitative autoradiography were employed in a serum-free medium to assess the effects of these fragments while light and electron microscopy studies served for morphological evaluations. It became evident that the fragment hPTH (1–34) enhanced the incorporation of [3H]thymidine, a fact that could be noted only in serum-free medium. The putative target cells for the effects of hPTH (1–34) were the chondroporogenitor cells which also appeared to have experienced a blockage in their differentiation into chondroblasts. Ultrastructurally, the latter cells responded in the formation of adherent profiles of plasma membranes, whereas the differentiated zone of the cartilage reduced its size. Using serum-free medium, hPTH (1–34) also brought about an inhibition in alkaline phosphatase activity, a fact that was not encountered in medium containing serum. By contrast, hPTH (28–48) had no mitogenic effect, although treated specimens revealed morphological changes in the chondroprogenitor cell zone along with an enhancement of cartilage cells hypertrophy. No significant effects on either mitogenecity or morphology could be noted in hPTH (53–84)-treated cultures.
Characterization of dimeric forms of human pituitary growth hormone by bioassay, radioreceptor assay, and radioimmunoassay
Authors: Brostedt Peter , Luthman Marguerite , Wide Leif , Werner Sigbritt , Roos Paul
Published: December 2008

Seven highly purified dimeric forms of human pituitary growth hormone, composed of the monomeric forms 20 K hGH, 22 K hGH and 24 K hGH linked together by noncovalent or covalent bonds, have been characterized by an in vitro bioassay (the Nb2 assay), a radioreceptor assay and a radioimmunoassay. Considerable differences in the ability to displace labelled recombinant hGH were observed in the radioreceptor assay. The seven dimeric forms varied over a range between 22 K hGH (most effective) and 20 K hGH. The three covalently-linked dimeric forms had nearly identical affinity constants. The mitogenic action of all but one of the hGH dimers in the Nb2 assay was in the same mutual order as the receptor binding activity in the radioreceptor assay. In the RIA, all dose-response curves were parallel except for those obtained with 20 K hGH and with the dimeric form (20 K-20 K)hGH. In this assay, dimeric variants of the constituents 22 K hGH and 24 K hGH were approximately twice as active as 22 K hGH on a molar basis, suggesting about the same affinity between the antibodies and each of the monomeric forms. Determination of the amino acid compositions of the dimeric forms provided support for their content of monomeric constituents as established earlier by electrophoretic analysis.
Effect of amiodarone on non-deiodinative pathway of thyroid hormone metabolism
Authors: Kannan Ram , Chopra Inder J. , Ookhtens Murad , Singh Bramah N.
Published: December 2008

Amiodarone, an iodine containing anti-arrhythmic drug, causes a significant decrease in molar ratio of daily production rates of T3 and T4 from 0.75 in controls to 0.36 in amiodarone-treated rabbits. A model was constructed from the above data which showed that metabolism of T4 via non-deiodinative pathways (e.g. tetraiodothyroacetic acid and/or conjugates) increased from 29% in untreated controls to 66% in amiodarone-treated rabbits. In this study, we have examined the metbolic clearance rate of tetraiodothyroacetic acid in rabbits given amiodarone (20 mg·kg−1·day−1 ip for 3 weeks) or saline (controls). Serum amiodarone and desethylamiodarone levels under the above experimental conditions were 0.20±0.067 and 0.17±0.058 mg/l, respectively, which were in the near-therapeutic range observed in humans. Control and amiodarone-treated rabbits were administered [125I]-tetraiodothyroacetic acid (10 μCi/rabbit) iv and blood was collected at 0.5, 1, 2, 4, 6, 10, 32 and 48 h. Serum tetraiodothyroacetic acid radioactivity was determined by trichloroacetic acid precipitation and ethanol extraction and metabolic clearance rates were calculated from the area under the curve of computer fits to tetraiodothyroacetic acid radioactivity data. Amiodarone treatment decreased metabolic clearance rates significantly from 0.107 ± 0.008 in controls to 0.074 ± 0.009 1/day in amiodarone-treated rabbits (p<0.05). However, when expressed per unit body weight (1·day−1·kg−1), the metabolic clearance rates were not significantly different between the controls and amiodarone-treated rabbits. The terminal serum elimination half-life in the two groups were similar (32.0 ± 6.7 h in controls vs 49.2 ± 12.4 h in amiodarone-treated). Our data suggest that a modest decrease in clearance rate and an increased production rate could result in an increase in serum tetraiodothyroacetic acid levels which may contribute to the reduction in 5'-monodeiodination of iodothyronines documented previously in amiodarone-treated animals. The marginal decrease in metabolic clearance rate of tetraiodothyroacetic acid found in this study suggests that the two-fold increase in the conversion of T4 metabolism to non-deiodinated metabolites/conjugates in amiodarone-treated rabbits results predominantly from an increase in production rate of tetraiodothyroacetic acid.
Incomplete virilization and subclinical mineralocorticoid excess in a boy with partial 17,20-desmolase/17 α-hydroxylase deficiency
Authors: de Lange W. E. , Doorenbos H.
Published: December 2008

A 17-year-old boy is described with impaired virilization and subclinical mineralocorticoid excess owing to combined 17,20-desmolase/17 α-hydroxylase deficiency. His basal plasma progesterone was 20.9 nmol/l (reference value 0.50-1.88), 17-hydroxyprogesterone 21.3 nmol/l (reference value 3.05-4.84), testosterone 6.85 nmol/l (reference value 14.1-22.0), and his excretion of tetrahydro-11-deoxycorticosterone 11.8 μmol/24 h (reference value 1.0-1.5). The differential effects of this combined enzyme deficiency on adrenal and testicular function were studied by ACTH stimulation, dexamethasone suppression, hCG stimulation, and suppression treatment with testosterone.
Isolated human growth hormone deficiency due to the hGH-I gene deletion with (type IA) and without (the Israeli-type) hGH antibody formation during hGH therapy
Authors: Nishi Yoshikazu , Masuda Hiroyuki , Nishimura Shinichiro , Kihara Mikio , Suwa Seizo , Tachibana Katsuhiko , Takeda Michiko , Okada Yoshiaki , Matsuda Ichiro
Published: December 2008

Three Japanese patients with isolated growth hormone deficiency from two different families were shown to be homozygous for deletion of the structural gene for human growth hormone (hGH-I gene). These three patients had the same restriction fragment length polymorphism haplotypes. In patient No. 1, the growth rate initially responded well to pituitary human growth hormone, but growth rapidly ceased concomitantly with the development of high levels of anti-hGH antibodies. He again responded well to recombinant methionyl hGH and recombinant hGH without the methionine residue, even though having high hGH antibodies. Two siblings (Patients No. 2 and 3) showed a rather good response to pituitary hGH treatment without hGH antibodies ever being detected (the Israeli-type). hGH-I gene deletions may not necessarily result in hGH antibody formation. Heterogeneity has been observed in isolated hGH deficiency due to hGH-I gene deletion. hGH-I gene analysis should not be limited to patients with hGH antibody formation and subnormal growth responses to hGH therapy.
Parlodel LAR® in the treatment of macroprolactinomas
Authors: Kocijancic Andreja , Prezelj Janez , Vrhovec Ivan , Lancranjan Ioana
Published: December 2008

Eight patients with macroprolactinomas were treated with a long-acting injectable form of bromocriptine, depot-bromocriptine (Parlodel LAR). With the exception of one male patient who had partial and shortlasting suppression of PRL levels after two injections and who underwent a second adenomectomy, the patients were given Parlodel LAR injections at 28-day intervals for six months. In all patients, there was a significant fall in serum PRL levels after the first injection. PRL secretion was suppressed to within the normal range in 3 of 7 patients on long-term treatment. PRL was consistently within the normal range in 2 patients from the sixth week and in one, from the 14th week onwards. In the other 4 of 7 patients, a marked suppression of PRL secretion, resumption of menses, and normal libido and potency were recorded. In 3 of 8 patients, no adverse effects were noted. Two patients reported short-lasting nausea, one vomiting, one constipation and in 2 patients, orthostatic dizziness occurred after the first injection. Subsequent injections, however, were well tolerated systematically and locally. Five patients had CT scan evidence of tumour shrinkage. A very large tumour virtually disappeared after the first injection of 50 mg depot-bromocriptine in one patient. The decrease of serum PRL secretion within the first 12 hours after injection did not predict normalization of serum PRL levels during long-term treatment, whereas the fall of serum PRL levels to below 5% of the basal values within the first months of treatment could be a good indicator for the final outcome.
Isolation of several fractions from human serum, inhibiting rabbit cartilage metabolism in vitro
Authors: Du Caju Marc V. L. , Rooman Raoul P.
Published: December 2008

In contrast to the well characterized serum stimulators of cartilage metabolism, information is scarce on the nature of circulating inhibitors. Human serum was fractionated by molecular sieving chromatography on Sephadex G-200, G-75, G-50 and Biogel P-4 gels. Six fractions with molecular weights of 150, 45, 30, 16, 9 and 1.2 kD inhibited [35S]sulphate incorporation into rabbit cartilage segments. All fractions but the smallest one exhibited their inhibitory effect only in the serum-stimulated cartilage. The 1.2 kD fraction impaired [35S]sulphate and [3H]methyl-thymidine incorporation into the cartilage segments in both stimulated and basal conditions. A seventh inhibitory fraction corresponded to the serum salt peak.
Identification and partial characterization of a growth hormone-binding protein in rat serum
Authors: Emtner Morgan , Roos Paul
Published: December 2008

A binding protein for growth hormone in serum from female rats has been identified and partially characterized. Serum was incubated with 125I-labelled human GH and fractionated on an agarose HPLC column. Complexes between the binding protein and 125I-hGH were detected as a peak eluted at a volume corresponding to a relative molecular weight of 159000 ± 11000 (N=8). The peak was not seen when the incubation was carried out in the presence of excess unlabelled hGH. The 125I-hGH bound with high affinity (Ka=0.87 ± 0.3 l/nmol;N=3) and the binding was time- and dose-dependent. Bound 125I-hGH was displaced by rat GH and bovine GH, but not by rat prolactin. The protein was not detected in radioreceptor assay by the commonly used polyethylene glycol precipitation technique and was not recognized by a monoclonal antibody raised against lactogenic receptors from female rat liver. Covalent cross-linking of 125I-hGH to serum revealed in SDS electrophoresis two labelled complexes with molecular weights of 62300 ± 3900 and 77600 ± 4100, respectively (N=10).
Autoantibodies to insulin do appear in non-diabetic patients with autoimmune disorders: Comparison with anti-immunoglobulin antibodies and other autoimmune phenomena
Authors: Di Mario Umberto , Perfetti Riccardo , Anastasi Emanuela , Contreas Giovanna , Crisà Laura , Tiberti Claudio , Amendolea Maria A. , Masala Cesare
Published: December 2008

Insulin- and anti-immunoglobulin-antibodies have been recently reported in pre-diabetic subjects: the former has been proposed as a predictive marker of Type I diabetes in non-diabetic-subjects. To evaluate the diabetes-related specificity of these antibodies, the presence of insulin autoantibodies, using a recently developed and highly sensitive competitive radioimmune assay, and of anti-immunoglobulin antibodies together with that of immune complexes and of other autoantibodies has been investigated in patients with organ- or non-organ-specific autoimmune diseases. One hundred and eleven serum samples were assayed from patients with Graves' disease, primary hypothyroidism, chronic autoimmune thyroiditis, Addison's disease, chronic autoimmune hepatitis, pernicious anemia, lupus erythematosus, and rheumatoid arthritis, together with 45 serum samples from normal subjects. From patients with autoimmune diseases, 32.4% of all sera revealed values of insulin autoantibodies above the limit of positivity (p<0.001); anti-immunoglobulin antibodies were present in 4.1% of patients (NS); immune complexes were found in 19.5% (NS) of all patients, but in 38% of patients with Graves' disease and chronic hepatitis (p<0.02). There was a trend for multiple autoantibody positivity to be associated with high levels of insulin autoantibodies (p<0.05). Thus, whereas contrary to expectation anti-immunoglobulin antibodies are not associated with non-diabetes-related autoimmune diseases, increased humoral immunoresponsiveness to endogenous insulin appears to be related to autoimmunity in general rather than restricted to Type I diabetes.
Lack of antibody formation during long-term subcutaneous treatment with the somatostatin analogue octreotide in acromegaly
Authors: van Liessum Peter A. , Swinkels Leon M. , Pieters Gerlach F. , Ross Alec A. , Smals Anthony G. , Benraad Theo J. , Kloppenborg Peter W.
Published: December 2008

Serum samples from 13 patients with active acromegaly on long-term sc treatment with octreotide (SMS 201-995, 1-36 months, mean daily dose 285 μg) were taken 12 h after the injection of their regular evening doses. Octreotide assay was performed using 125I-Tyr-SMS and a polyclonal rabbit anti-serum. For assessment of antibody formation both serum coated charcoal adsorption (adsorption of free octreotide) and polyethylene glycol precipitation (precipitation of IgG complexes) were used. The mean binding percentage in the patients proved to be similar to that of 5 healthy volunteers (p>0.10). No specific binding was detected, whatever method used. No correlation was found between the binding percentages and octreotide serum levels, duration of octreotide treatment or daily octreotide dose (p>0.10). These results strongly suggest that clinically relevant endogenous antibody formation is not a frequent event during long-term sc treatment of acromegalic patients with octreotide.
Ageing does not influence the ultrashort feedback control of GnRH secretion in vitro
Authors: Messi Elio , Zanisi Mariarosa , Martini Luciano
Published: December 2008

Evidence indicates that long and short feedback systems are altered in the aged male rat. Data also indicate the existence of an ultrashort feedback mechanism controlling GnRH secretion. The present experiments were performed to test whether the ultrashort feedback control of GnRH is operating also in old male rats. Mediobasal hypothalami of 18-month-old male rats were perifused in vitro either in the presence or in the absence of a GnRH agonistic analogue (Buserelin: [D-Ser(TBU)6, Des-Gly10]GnRH ethylamide) and stimulated with 5-min pulses of K+ (for a total of six pulses) in order to test their ability to release GnRH. The hypothalamic fragment was exposed to the GnRH analogue either for a part of the experimental period (at the beginning or at the end) or for the whole duration of the perifusion. In both cases, the presence of the analogue diminished or totally abolished the responses to K+ stimulation. This is in line with the results obtained in young animals. The data suggest that the ultrashort feedback mechanism controlling GnRH release is normally functioning also in aged male rats despite the fact that other types of feedback mechanisms (long and short loop) are substantially altered.
Effects of angiotensin II, ACTH, and KCl on the adrenal renin-angiotensin system in the rat
Authors: Sasamura Hiroyuki , Suzuki Hiromichi , Kato Ryuichi , Saruta Takao
Published: December 2008

Angiotensin II, ACTH and potassium chloride were administered to rats for 6 days and the effects on adrenal renin-like activity and adrenal angiotensin II/III immunoreactivity were investigated. Rats infused with angiotensin II(140 pmol/min) either ip or sc showed increases in adrenal angiotensin II/III immunoreactivity (p<0.05) and plasma aldosterone concentration (p<0.05), but no change in adrenal renin-like activity. Captopril treatment of angiotensin Il-infused rats caused a slight decrease in angiotensin II/III immunoreactivity which did not reach statistical significance. In contrast, rats treated with ACTH (Cortrosyn-Z, 3 IU/day, sc) showed an increase in adrenal renin-like activity (p<0.01), but no significant change in adrenal angiotensin II/III immunoreactivity. Rats treated with KCl in drinking water showed increases (p<0.05) in adrenal renin-like activity, adrenal angiotensin II/III immunoreactivity, and plasma aldosterone. These results suggest that angiotensin II, ACTH and potassium, three major regulators of aldosterone secretion by the adrenal gland, have different effects on the adrenal renin-angiotensin system when administered in vivo.
Lipolysis in isolated epididymal adipocytes from genetically obese Zucker rat treated with 3,5,3'-L-triiodothyronine
Authors: Lebrazi Halima , Chomard Philippe , Dumas Paul , Autissier Nicole
Published: December 2008

Glycerol released by isolated epididymal adipocytes was measured in 6-8 weeks old genetically obese (fa/fa) and lean (C.c.a/-) male Zucker rats, ip treated or not treated with T3 (0.46, 2.3 and 4.6 nmol/100 g in a single injection or 4.6 nmol · (100 g)−1 · day−1 for 5 days). In the non-treated rats, lipolysis was less stimulated by adrenalin or isoproterenol in obese than in lean rats, whereas it was stimulated by theophylline up to the same level in both kinds of rats. A single injection of the T3 (highest dose) increased isoproterenol-induced lipolysis in the lean but not in the obese rats. The 5-day T3 treatment caused a stimulation of the adrenalin- or isoproterenol-induced lipolysis in both kinds of rats. However, the stimulation was lower in the obese than in the lean rats. This treatment increased theophylline-induced lipolysis in the lean but not in the obese rats. It did not affect significantly the theophylline-induced lipolysis stimulated by adrenalin or isoproterenol in either obese or lean rats. These findings show that mild hypothyroidism of obese rat is partly responsible for the impaired sensitivity of its adipose tissue to lipolytic drugs. The apparently low T3 sensitivity of obese rat adipose tissue is discussed.
Pyridostigmine enhances, but does not normalise, the GH response to GH-releasing hormone in obese subjects
Authors: Castro R. C. , Vieira J. G. H. , Chacra A. R. , Besser G. M. , Grossman A. B. , Lengyel A. M.J.
Published: December 2008

Obese patients are characterised by several neuroendocrine abnormalities, including characteristically a decrease in growth hormone responsiveness to GH-releasing hormone. In normal subjects, the GH response to GHRH is enhanced by the acetylcholinesterase inhibitor, pyridostigmine. We have studied the effect of this drug on GH secretion in gross obesity. Twelve obese patients were studied (mean weight 156% of ideal) and compared with a group of 8 normal volunteers. Each subject was initially studied on two occasions, in random order, with GHRH (1–29) NH2 100 μg iv alone and following pretreatment with pyridostigmine 120 mg orally one hour prior to GHRH. In obese patients, the GH response to GHRH was significantly blunted when compared to controls (GH peak: 20 ± 4 vs 44 ± 16 μg/l; mean ± sem). After pyridostigmine, the response to GHRH was enhanced in the obese subjects, but remained significantly reduced compared to non-obese subjects treated with GHRH and pyridostigmine (GH peak: 30 ± 5 vs 77 ± 20 μg/l, respectively). In 6 subjects, higher doses of GHRH or pyridostigmine did not further increase GH responsiveness in obese patients. Our results suggest that obese patients have a disturbed cholinergic control of GH release, probably resulting from increased somatostatinergic tone. This disturbed regulation may be responsible, at least in part, for the blunted GH responses to provocative stimuli.
Thyroid sonography in autoimmune thyroiditis. A prospective study on 123 patients
Authors: Nordmeyer Johann P. , Shafeh Taher A. , Heckmann Christian
Published: December 2008

Thyroid sonography was used to assess 2322 patients attending our clinic over a 3-year period. Sonography, in combination with clinical and laboratory findings, enabled us to detect autoimmune thyroiditis in 123 patients, 67 of whom could be classified as euthyroid, 17 as latent hypothyroid, and 39 as overtly hypothyroid. Consequently without the use of sonography (or thyroid antibody measurements) it would not have been possible to make a diagnosis in over half of our patients with autoimmune thyroiditis. Sonography was also of considerable value in establishing the absence of autoimmune thyroiditis as out of the 2322 patients we examined, autoimmune thyroiditis could be excluded on the basis of sonography alone (absence of diffuse hypoechoicity) in 1962 (84%). Thyroid volume ranged from < 5 to 112 ml with the majority of patients having a volume of 21-30 ml and the overtly hypothyroid group showing a shift to smaller volumes. The data suggested that thyroid volume changes over the range of the disease from euthyroid to overtly hypothyroid.