bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolation and partial characterization of six somatomedin-like peptides from human plasma Cohn fraction IV
Authors: Blum Werner F. , Ranke Michael B. , Bierich Jürgen R.
Published: December 2008

Abstract. Six somatomedin-like peptides were purified from human plasma Cohn fraction IV by a six-step procedure which included ethanol precipitation, reversed-phase extraction, gel filtration, chromatofocusing and reversed-phase high pressure liquid chromatography (HPLC). Purification was monitored with a competitive protein binding assay using a crude preparations of somatomedin carrier protein. The peptides isolated were homogeneous by reversed-phase HPLC and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Their apparent isoelectric points determined by chromatofocusing were 9.2 (Sm I), (Sm II), 8.2 (Sm III), 6.7 (Sm IV), 6.3 (Sm V), and 6.15 (Sm VI). SDS-PAGE under reducing conditions revealed that they are composed of a single peptide chain with apparent molecular weights of 6800 for Sm I, II and IV and 6400 for Sm III, V, and VI. They were equally potent in the porcine costal cartilage in vitro bioassay. The basic peptides (Sm I–III) were significantly more active in radioimmunoassays for somatomedin C (SmC) and insulin-like growth factor I C-peptide (IGF-I (30–41)), while only the slightly acidic peptides were active in a radioimmunoassay for insulin-like growth factor II C-peptide (IGF-II (33–40)). When receptor binding was tested with human placental cell membranes and Sm III as tracer, the basic peptides were significantly more potent than Sm IV–VI. With rat liver cell membranes and Sm V as tracer the slightly acidic peptides were more potent.

These findings suggest 1) that human plasma may contain other somatomedin-like peptides besides the major components IGF-I/SmC and IGF-II, and 2) that the basic peptides are structurally related to IGF-I/SmC and the slightly acidic peptides are related to IGF-II.
Enhancement of vitamin D3 effect on bone metabolism in weanling rats orally administered zinc sulphate
Authors: Yamaguchi Masayoshi , Sakashita Teruyuki
Published: December 2008

Abstract. The interaction of vitamin D3 and zinc on bone metabolism was investigated in the femur of weanling rats. Oral administration of vitamin D3 (1.0 μg/100 g body weight) did not cause any increase in the zinc accumulation in the femoral tissue following treatment with zinc sulphate (1.0 mg Zn/100 g). Administration of vitamin D3 or zinc produced significant increases the alkaline phosphatase activity and DNA content of the femoral diaphvsis but not of the epiphysis. The increase in alkaline phosphatase activity was enhanced additionally by simultaneous administration of vitamin D3 and zinc. Moreover, the increase in DNA content was enhanced markedly (about 4 times) by these treatments. At a dose of 0.5 μg of vitamin D3 per 100 g, DNA content was at the control level. This level was increased about 2 times by simultaneous administration of zinc (1.0 mg/100 g). The increase in alkaline phosphatase activity following simultaneous administration of vitamin D3 and zinc was significantly inhibited by treatment with cycloheximide, actinomycin D, or mitomycin C. Also, the increase in DNA content was completely inhibited by mitomycin C treatment. The present data suggest that the combination of vitamin D3 and zinc has a multiple effect on the stimulation of bone growth and mineralization in weanling rats, and that this effect is based on a stimulation of the DNA synthesis in bone cells.
ACTH and prolactin deficiency
Authors: Puig Manuel L. , Webb Susan M. , del Pozo Carlos , Espinosa José Rodríguez , Martínez Ma Jesús , de Leiva Alberto
Published: December 2008

Abstract. A 35 year old woman suffering from ACTH and prolactin (Prl) deficiency is described. Her symptoms of adrenal insufficiency appeared gradually after her first pregnancy in 1970; however, she conceived twice more and delivered healthy babies in 1972 and 1974, which she could not breast feed due to lack of milk. During an episode of pneumonia in 1977 she suffered acute adrenal insufficiency, after which she began treatment with hydrocortisone. Her pituitary reserve for TSH, GH, LH and FSH was normal, but her ACTH and Prl levels were undectable and did not respond to acute iv challenges of corticotrophin-releasing factor (CRF) and TRH, respectively. Autoantibodies, including antilactotroph titres, were negative, except for a positive pituitary immunofluorescence to ACTH. There was also no ACTH stimulation to a prolonged infusion of CRF followed by an acute iv bolus. These results, together with the gradual onset of symptoms which worsened after each pregnancy, suggest a possible autoimmune aetiology of her pituitary ACTH and Prl deficiencies.
An intrasellar pituitary tumour producing metastases in liver, bone and lymph glands and demonstration of ACTH in the metastatic deposits
Authors: Casson I. F. , Walker B. A. , Hipkin L.J. , Davis J. C. , Buxton P. H. , Jeffreys R. V.
Published: December 2008

Abstract. We report the history, laboratory and histological findings in a man who presented with Cushing's disease. Despite removal of the primary pituitary tumour, his disease progressed and after bilateral adrenalectomy, he became pigmented and plasma ACTH levels remained elevated. He had further pituitary surgery and radiotherapy, to relieve compression of the optic chiasma. Plasma ACTH levels remained elevated. He developed liver, bone and lymph gland metastases and after an acute paraparesis due to spinal metastases he died. Immunoperoxidase staining techniques demonstrated ACTH in the pituitary recurrence and metastases. The combination of bone, liver and lymph node metastases has not previously been reported, nor has ACTH been reported before in metastases from a primary intrasellar tumour.
Blocking effect of naloxone, dihydroergotamine and adrenalectomy in lithium-induced hyperglycaemia and glucose intolerance in the rat
Authors: Fontela T. , Hermida O. García , Gómez-Acebo J.
Published: December 2008

Abstract. The direct effect of lithium administration on plasma glucose levels and glucose-induced insulin release, and the role of opioid and amine systems in these effects were examined in rats. Naloxone, an opiate antagonist, and dihydroergotamine, an alpha-adrenergic blocking agent, reversed the hyperglycaemia as well as the inhibition of glucose-stimulated insulin release induced by lithium. In adrenalectomized rats, administration of lithium induced hypoglycaemia and not hyperglycaemia as in the intact rats. The results suggest that the interaction of secreted endorphins with the sympathetic nervous system is the likely cause of the hyperglycaemia and the inhibition of the glucose-stimulated insulin release induced by lithium.
Ovarian multifollicularity, high LH and androgen plasma levels, and anovulation are frequent and strongly linked in adolescent irregular cycles
Authors: Venturoli S. , Porcu E. , Fabbri R. , Paradisi R. , Gammi L. , Passarini M. , Orsini L. F. , Flamigni C.
Published: December 2008

Abstract. Ninety-seven adolescents (0.5–6.0 years in gynaecological age) suffering from various kinds of menstrual irregularities were studied and compared with 20 adults by performing ovarian ultrasonography and plasma hormonal determinations.

High percentages of multifollicularity (57.7%) and enlarged ovaries (46.3%) were found in the entire group of adolescents.

Adolescents with multifollicular ovaries (more than 4 cystic areas) showed higher percentages of luteinizing hormone (LH: 32%), testosterone (T: 34%), and androstenedione (A: 43%) levels exceeding the upper normal adult range than subjects with homogeneous (less than 4 cystic areas) ovaries (LH: 12%, T: 10%, A: 19%, respectively).

Ovulation can further discriminate the adolescents: in fact, adolescents with homogeneous ovaries and ovulatory cycles have a hormonal pattern almost identical to that of adults. On the contrary, subjects with multifollicular ovaries and anovulatory cycles show low values of follicle-stimulating hormone (FSH) and high values of LH, T and A, significantly different from those in ovulatory subjects with homogeneous ovaries (P < 0.005) and from those in adults (P < 0.005).
The effect of oestrogen and relaxin on uterine and cervical enzymes: collagenase, proteoglycanase and β-glycuronidase
Authors: Too Catherine K. L. , Kong Julianne K. , Greenwood F. C. , Bryant-Greenwood Gillian D.
Published: December 2008

Abstract. Relaxin (Rlx) classically causes uterine quiescence during pregnancy and cervical dilatation prior to parturition. Its actions involve major changes in the components of the extracellular matrix of these tissues. The activities of three enzymes, collagenase, proteoglycanase and β-glucuronidase, major determinants of the integrity of the extracellular matrix have been measured in the rat uterus and cervix in different reproductive states. The results show that there are marked differences in the changes of these enzymes occurring in the uterus and cervix during the course of pregnancy and the puerperium. It was not possible to directly relate these changes to a single hormonal event over this period of major endocrine fluctuations. Two models have therefore been used in an attempt to delineate the effects of oestrogen and Rlx on the tissue enzyme levels or their secretion into culture medium. In the first model cyclic animals were treated with oestrogen alone or oestrogen followed by Rlx and tissue enzyme levels measured. The addition of Rlx treatment reversed an inhibiting effect of oestrogen alone on both uterine and cervical collagenase and proteoglycanase activities, at the same time as completely obliterating the stimulating effect of oestrogen on uterine and cervical β-glucuronidase activity. A second model used in vivo oestrogen priming of cyclic rats followed by in vitro Rlx treatment and measurement of the enzymes secreted into the culture medium over 7 days. The results showed as in the first model that Rlx treatment could in particular overcome the inhibiting effect of oestrogen on uterine proteoglycanase secretion without affecting β-glucuronidase levels. In contrast, the effect of Rlx on the cervix was to decrease collagenase and proteoglycanase secretion whilst not affecting the β-glucuronidase levels.
Long-term hormone implant therapy – effects on lipoproteins and steroid levels in post-menopausal women
Authors: Fletcher C. D. , Farish E. , Hart D. M. , Barlow D. H. , Gray C. E. , Conaghan C. J.
Published: December 2008

Abstract. Lipoprotein and steroid hormone levels were measured in 61 bilaterally oophorectomised women who had been treated for 3 years with implants containing either oestradiol alone or oestradiol plus testosterone. The lipoprotein levels associated with each of the two therapy regimens were compared. In addition, lipoproteins were measured in 67 untreated bilaterally oophorectomised age-matched women and compared with those of the treated women. Despite the high oestradiol levels produced by both types of implant, the only significant finding was a reduced LDL cholesterol in the oestrogen/testosterone treated group as compared with that of the untreated group.
Feedback effects of gonadal steroids and pituitary LH-releasing hormone receptors in the streptozotocin-induced diabetic rat
Authors: Bowton P. A. , Bryant K. R. , Whitehead S. A.
Published: December 2008

Abstract. The effects of streptozotocin (STZ)-induced diabetes mellitus on the positive feedback action of steroids on luteinizing hormone (LH) secretion have been investigated in the oestrogen-primed ovariectomized rat. Rats treated with 40 mg/kg STZ 2 weeks before experimentation showed an attenuated LH surge in response to progesterone, an effect only partially restored by insulin replacement. When the same dose of the drug was injected just 24 h before the progesterone treatment it had no effect on the LH surge, while a high dose of 80 mg/kg STZ completely abolished the positive feedback action of the steroid. Insulin treatment did not reverse this effect. In parallel the effects of 2-week and 24-h diabetes on pituitary LH-releasing hormone (LRH) receptors were studied. Pituitary binding of a long acting LRH analogue was reduced in the 2-week diabetic animals, although a more dramatic reduction was observed in the rats treated with the high dose of STZ 24 h before testing. The results suggest that diabetes impairs the positive feedback effects of gonadal steroids resulting in a reduced release of LRH. However, the impairment is unlikely to be caused simply by hyperglycaemia but by non-specific toxic side effects of STZ and/or other metabolic changes associated with diabetes.
Antigenic determinants on thyroglobulin recognized by T cells in patients with chronic thyroiditis
Authors: Shimojo Naoki , Kohno Yoichi , Tarutani Osamu , Sasaki Nozomu , Nakajima Hironori
Published: December 2008

Abstract. It was found that the proliferating cells to thyroglobulin (Tg) in patients with chronic thyroiditis are confined to a T cell subpopulation. Then, we attempted to characterize the antigenic determinants of Tg recongized by T cells from patients with chronic thyroiditis by Tg-induced DNA-synthetic response. T cells from patients could respond to Tgs from whales, pigs and chickens as well as to human Tg. These findings indicated that epitopes on Tg recognized by T cells were shared by Tgs from various species. In addition, the T cells from different individuals varied in specificity.
Cortical bone mineral content in primary hyperparathyroidism. Changes after parathyroidectomy
Authors: Mautalen Carlos , Reyes Harry Romero , Ghiringhelli Gualterio , Fromm Günther
Published: December 2008

Abstract. The bone mineral content (BMC) of 35 patients with primary hyperparathyroidism (PHPT) was measured at the mid radius (95% cortical bone) by photon absorptiometry of a 241Am source. The majority of the patients had an overt disease of moderate to severe degree. Average serum calcium of the group was 12.3 mg/100 ml (range 10.6 to 18.0 mg/100 ml). The percentage of normality of the BMC was (Av ± 1 sd) 75.1 ± 13.0% for the whole group.

The average increment of BMC in 14 patients 9 to 26 months after parathyroidectomy was 9.9%, with a wide dispersion. However a highly significant negative correlation (r: 0.83; P < 0.01) was found between the initial bone mass and the percentage increment per month after surgery. No further gain was observed 2 years after parathyroidectomy except in one patient with an extremely severe bone loss. In spite of the gain obtained after surgery the bone mass remained markedly diminished in most patients showing that the cortical bone loss caused by PHPT is mainly irreversible.
Counterregulation of insulin-induced hypoglycaemia in primary hypothyroidism
Authors: Clausen Nina , Lins Per-Eric , Adamson Ulf , Hamberger Bertil , Efendić Suad
Published: December 2008

Abstract. Hypothyroidism has been alleged to modulate insulin action and influence the secretion of growth hormone and catecholamines. We recently investigated the influence of hypothyroidism on glucose counterregulatory capacity and the hormonal responses to insulin-induced hypoglycaemia in 6 patients with primary hypothyroidism (age 32–52 years, TSH-values 66–200 mU/l). Hypoglycaemia was induced in the hypothyroid state and again when the subjects were euthyroid. After an overnight fast a constant rate infusion of insulin (2.4 U/h) was given for 4 h. Glucose was measured every 15 min and insulin, C-peptide, glucagon, epinephrine, norepinephrine, growth hormone and cortisol every 30 min for 5 h.

During insulin infusion somewhat higher concentrations of the hormone were obtained in the hypothyroid state and simultaneously glucose levels were 0.5 mmol/l lower. As expected, basal norepinephrine levels were higher in hypothyroidism. However, no increase in circulating norepinephrine during hypoglycaemia was registered in the two experiments. The responses of counterregulatory hormones showed an enhanced response of cortisol, similar responses of growth hormone and epinephrine while the glucagon response was paradoxically impaired. Our findings suggest that hypothyroidism alters insulin metabolism, and that the glucagon response to hypoglycaemia is impaired in this condition.
Interindividual variation in the absorption of glibenclamide in man
Authors: Ikegami Hiroshi , Shima Kenji , Tanaka Akira , Tahara Yasuhiro , Hirota Meisei , Kumahara Yuichi
Published: December 2008

Abstract. To investigate the interindividual variation in the absorption of sulphonylureas and its relation to unexpected hypoglycaemia during therapy with these drugs, serum concentration profile of glibenclamide, as well as plasma glucose and insulin response after an oral intake of glibenclamide were studied in 17 patients with non-insulin-dependent diabetes mellitus. In 12 patients glibenclamide was rapidly absorbed, reaching a peak concentration of 138.0 ± 15.8 ng/ml (mean ± sem) at about 2 h. However, in 5 patients the absorption of glibenclamide was delayed and reached a serum peak of 134.1 ±29.5 ng/ml at later than 4 h. This delayed absorption was reproducible. There were no significant differences in age, duration of diabetes, per cent of ideal body weight, fasting plasma glucose or HbA 1C between the rapid absorption group and the delayed group. However, autonomic nerve function, assessed by coefficient of variation of R-R intervals, was significantly impaired in the latter group in comparison with the former. Plasma glucose and insulin response to glibenclamide was also delayed in the delayed absorption group.
Characterization of immunoreactive corticotropin and corticotropin-releasing factor in human adrenal and ovarian tumours
Authors: Suda Toshihiro , Tomori Naoki , Yajima Fumiko , Odagiri Emi , Demura Hiroshi , Shizume Kazuo
Published: December 2008

Abstract. The distribution of immunoreactive ACTH (I-ACTH) and corticotropin-releasing factor (I-CRF) in the human adrenal was determined and these peptides were indentified in adrenocortical adenomas from patients with primary aldosteronism, Cushing's syndrome, and ovarian tumours and compared with the results in phaeochromocytomas. I-ACTH and I-CRF, mainly localized in the adrenal medulla from patients without endocrine disorders, showed a good correlation with the epinephrine concentrations. I-ACTH and I-CRF were present in all the above-mentioned tumours. Gel filtration of I-ACTH and I-CRF from these tumours showed the presence of large molecular weight forms of these peptides as well as authentic peptides. The trypsinization study of I-CRF from phaeochromocytoma suggested that such large molecular weight forms were the precursors of authentic CRF. High performance liquid chromatography showed I-CRF in these tumours to be similar to hypothalamic CRF. Phaeochromocytoma tissue slices incorporated [3H]leucine into ACTH and CRF. These findings raised the possibility that I-ACTH and I-CRF are synthesized and processed in phaeochromocytoma.
Lipids, apolipoproteins and steroids in serum and in fluid from stimulated and non-stimulated human ovarian follicles
Authors: Enk L. , Crona N. , Olsson J.-H. , Hillensjö T.
Published: December 2008

Abstract. Steroid production depends on the cholesterol (CH) substrate supplied by circulating lipoproteins which are internalised in the cells by receptormediated mechanisms. Low density lipoproteins (LDL) stimulate progesterone production in vitro. However, studies on follicles indicate low levels of LDL in follicular fluid (FF1).

In the present study FF1 was obtained by ultrasoundguided punctures just before ovulation from 17 women participating in an in vitro fertilization programme. Serum was obtained simultaneously. Follicular development was stimulated with hMG-HCG or clomiphenehMG-hCG combinations. In another 8 women FF1 was collected in connection with surgery for sterilization. FF1 levels of CH, triglycerides (TG), phospholipids (PL), apolipoprotein Al and B (apoAl; apoB), oestradiol and progesterone were assayed in both groups as were the corresponding serum levels in the stimulated patient group.

The FF1 levels of apoAl, TG and PL were approximately half of the levels in HDL in normal serum in both groups. However, CH was slightly lower in the stimulated group. ApoB was not detectable in FF1. Oestradiol was similar in both groups while progesterone was much higher in the stimulated than in the non-stimulated cycles. FF1 levels of apoAl correlated positively to CH and PL in both groups and to progesterone in the stimulated follicles, while the correlation was negative in the other group. The absence of apoB and the levels of CH, TG, PL and apoA1 1 indicate that high density lipoprotein (HDL), but not LDL is present in FF1. The supply of CH needed for the increased production of progesterone in the granulosa cells in the late follicular phase has to be explained by mechanisms other than transportation with LDL particles. It is possible that gonadotrophins facilitate the delivery of CH from HDL, which has been shown to penetrate the 'blood-follicle' barrier.
Effect of 1α,24(R)-dihydroxyvitamin D3 on calcium metabolism in the rat
Authors: Yamada S. , Bonjour J.-P. , Fleisch H.
Published: December 2008

Abstract. It has been suggested that 1α,24(R)-dihy droxyvitamin D3 (1,24(OH)2D3), a chemically synthesized vitamin D analogue, may have the property to enhance whole-body Ca retention and may thus be of use in osteoporosis. In order to test this hypothesis the main fluxes of Ca metabolism were measured in vitamin D-replete rats injected ip with 1,24(OH)2D3 at daily doses of 25, 50 and 100 pmol for 10 days. As compared with pair fed control animals, rats treated with 1,24(OH)2D3 displayed a significant rise in net intestinal absorption of Ca and in urinary excretion of Ca, and increase in bone resorption but no significant change in bone formation. Whole body Ca retention was not changed at 25 pmol/day and showed a trend to decrease at 50 and 100 pmol/day. In conclusion these results do not suggest that among available vitamin D analogues, 1,24(OH)2D3 would be particularly useful for increasing bone Ca retention in osteoporosis.
Dysregulation of plasma pro-opiomelanocortin-related peptides in neurotic depression
Authors: Genazzani Andrea R. , Petraglia Felice , Sinforiani Elena , Brambilla Francesca , Facchinetti Fabio , Nappi Giuseppe
Published: December 2008

Abstract. In order to assess whether a central hypothalamic impairment could account for the pro-opiomelanocortin (POMC)-related peptide over-secretion in depressive disorders, plasma B-lipotropin (B-LPH), B-endorphin (B-EP) and cortisol concentrations were measured in 9 patients affected by neurotic depression: a) every 4 h over a 24-h period: b) in response to insulin-induced hypoglycaemia (0.1 IU/kg body weight), and c) during dexamethasone (DXM) administration (0.5 mg × 4/day for 2 days). Eight age-matched healthy volunteers (controls) were also studied. B-EP and B-LPH were determined by specific radioimmunoassays after plasma extraction and gel chromatography. Compaired with the controls, the patients showed a 3 times higher plasma B-EP, twice the normal B-LPH levels, and a 20% cortisol increase. The neurotic depressed patients showed and evening-related decrease in the levels of the 3 hormones, expressed as mean values, similar to that in the controls, whereas the single cosinor analysis revealed a significant circadian rhythm of B-LPH and B-EP only in 3 and 2 patients, respectively. Insulin-induced hypoglycaemia (ITT) stimulated the release of B-LPH and cortisol in both groups, whereas the B-EP increase was absent in the patients. DXM reduced plasma cortisol and B-LPH levels in controls and patients, but in the latter it failed to reduce the B-EP concentrations. The present data indicate that neurotic depressed patients are characterized by increased activity of the hypothalamic-pituitary-adrenal axis, with maintained circadian rhythmicity. The B-EP unresponsiveness to ITT and DXM contradicts the normal responses of B-LPH and cortisol to the same tests and suggests a dysregulation of plasma B-EP secretion in neurotic depressed patients.
in Comparison between pituitary computed tomographic findings and tests of hypothalamo-pituitary function 72 patients with hyperprolactinaemia
Authors: Ghigo E. , Ciccarelli E. , Bianchi S. D. , Gatti G. , Molinatti G. M. , Massara F. , Müller E. E. , Camanni F.
Published: December 2008

Abstract. To verify the diagnostic capacity of some dynamic tests of the prolactin (Prl) secretion, the findings obtained by high-resolution computed tomography (CT) were compared with results obtained from tests using nomifensine (NOM) domperidone (DOM) and thyrotrophin-releasing hormone (TRH) in 72 patients with pathological hyperprolactinaemia.

None of the patients with tumours had a positive Prl response to NOM or to DOM administration; however, a positive response to these tests was present in only 24 and 41%, respectively, of the patients with normal CT picture. The results of TRH testing were similar to those obtained with DOM. Different neuroendocrine patterns were disclosed by comparing pituitary Prl and thyrotrophin (TSH) responses to DOM: 1) some subjects had a reduced Prl response together with an exaggerated or normal TSH response to DOM; they comprised patients with tumour, empty sella, and normal CT picture; 2) other patients with normal CT picture had a positive Prl and a normal TSH response to DOM.

These results demonstrate that a negative Fri response to NOM and DOM characterizes all patients with adenoma; however, the tumour-like responses in patients with no visible tumours seem to reduce the diagnostic value of these tests, unless the latter may predate the radiological appearance of an adenoma. On the other hand, a positive Prl and a normal TSH response to DOM exclude the presence of a pituitary tumour. This diagnostic finding is strengthened by the positive response also to NOM. Whatever may be the diagnostic validity of dynamic tests, they provide sound information on the functional state of dopamine neurotransmission.
Single-dose metyrapone test at 06.00 h: an accurate method for assessment of pituitary-adrenal reserve
Authors: Dickstein Gabriel , Lahav Michal , Orr Zila Shen
Published: December 2008

Abstract. One dose of metyrapone (1.5 g) administered at 06.00 h, with subsequent measurement of 11-deoxycortisol and 17-hydroxycorticosteroid (17-OHCS) levels in plasma at 12.00 and 14.00 h, allowed accurate assessment of the pituitary-adrenal reserve. Normal response was defined as achieving a serum 17-OHCS level of more than 10.0 μg/100 ml and a 11-deoxycortisol level of more than 6.0 μg/100 ml at either 12.00 or 14.00 h. These criteria are based on a group of 18 persons with normal pituitary-adrenal axis, and 86 additional cases responded in this normal range. In this group of 104 subjects, 11-deoxycortisol levels rose to 9.2 ± 3.5 μg/100 ml at noon and 17-OHCS levels to 15.4 ± 4.7 μg/100 ml at 14.00 h. Post-metyrapone 17-OHCS levels were significantly higher than normal cortisol levels at these times (P < 0.001) and than those observed at 08.00 h on the day of the test, demonstrating stimulation of adrenal corticoid production in addition to blockade of cortisol production by metyrapone. Thirty-one patients found to suffer from secondary adrenal failure showed impaired response. All these patients had limited pituitary-adrenal reserve, either proven by other pituitary-adrenal tests or implicated by severe pituitary disease.
Combined FSH and LH secreting pituitary adenoma in a young fertile woman without primary gonadal failure
Authors: Moses Nora , Goldberg Victoria , Gutman Raúl , Cácamo Darío
Published: December 2008

Abstract. A 28 year old fertile woman presented with a history of amenorrhoea and galactorrhoea, and an enlarged pitutiary fossa. Serum FSH and LH were repeatedly elevated both basally (32 and 44 mIU/ml) and after LRH (peak values, 108 and 420 mIU/ml). One mg of oestradiol (E2) benzoate im daily for 5 days failed to lower basal or LRH-stimulated serum gonadotrophins. Serum E2 was 170 pg/ml, basal serum prolactin (Prl) was 30 ng/ml and responded briskly to TRH (peak value 103 ng/ml).

An 0.8 × 0.8 cm tumour was selectively excised by transsphenoidal surgery. Menses reappeared soon afterwards accompanied by normalization of serum FSH and LH plus biochemical evidence of ovulation.

Specific immunostaining of tumoural cells was achieved with either FSH or LH antiserum, and adequate suppression of staining was obtained after preabsorbing each antiserum with and excess of its respective antigen. Our patient appears to be the first documented female with a combined FSH and LH producing pituitary tumour and no prior evidence of primary gonadal failure.
Treatment of Turner's syndrome with methionyl human growth hormone for six months
Authors: Takano Kazue , Hizuka Naomi , Shizume Kazuo
Published: December 2008

Abstract. Twenty patients with Turner's syndrome were treated with methionyl human growth hormone (met-hGH) produced by recombinant DNA technology. Plasma non-esterified fatty acid (NEFA) (mean ± sem) increased significantly from 0.52 ± 0.06 to 1.30 ± 0.09 mEq/l at 4 h after the first administration of 4 IU of met-hGH (P <0.001). Basal plasma somatomedin C (SM) levels were within the normal range; however, they increased significantly at 24 h after the first three daily injections of 4 IU of met-hGH (basal, 0.92 ± 0.14; 24 h, 1.39 ± 0.16; 48 h, 1.68 ± 0.19; 72 h, 1.91 ± 0.22 U/ml; P < 0.001). For long-term treatment, the patients were given 16 IU of met-hGH per week for 6 months. The height increase during treatment was greater in 16 patients, but smaller in 4 than before treatment. The heights increased between 1.4 and 3.7 cm during 6 months of treatment, which corresponds to between 2.8 and 7.4 cm/year. The mean increase of 5.7 ± 0.4 cm/year was greater than the pretreatment value of 3.7 ± 0.2 cm/year (P <0.001). There was a positive correlation between growth rate and maximum increase in SM (r = 0.51, P < 0.05). Antibody against hGH appeared in 3 patients after 2 months; 10 of the 20 patients had antibody after 6 months of treatment. However, the antibody did not suppress the growth effect of met-hGH. Otherwise there were no significant changes in physical, blood, or urine examinations.

These results indicate that hGH treatment is useful for the acceleration of growth velocity in patients with Turner's syndrome.
Repetitive and continuous administration of human corticotropin releasing factor to human subjects
Authors: Schopohl J. , Hauer A. , Kaliebe T. , Stalla G. K. , von Werder K. , Müller O. A.
Published: December 2008

Abstract. ACTH secretion was studied in response to repetitive and continuous administration of human corticotropin releasing factor (CRF) in 14 healthy volunteers and 2 patients with secondary adrenal insufficiency. ACTH increases during repetitive CRF administration were within the same range in normal subjects independent of the intervals (60– 180 min) between the CRF pulses (100 μg iv). When CRF was infused continuously (100 μg/h for 3 h) after an initial CRF bolus injection (100 μg iv), ACTH and cortisol remained elevated during the infusion at a nearly constant level (ACTH: 60 ± 5 pg/ml; cortisol: 21.2 ± 1 μg/dl; x̄ ± se). A second CRF bolus injection at the end of the infusion did not lead to a significant further increase of ACTH and cortisol levels. This shows that there is no desensitisation or depletion of a ready releasable pool, as it is observed with other pituitary hormones after releasing hormone stimulation. Pulsatile administration of CRF in 2 patients with secondary adrenal insufficiency due to previous cortisol or glucocorticoid excess, respectively, revealed a blunted response to the first pulse which became normal after the following pulses. The latter could not be sustained until the next morning without CRF given overnight. These findings point to a hypothalamic defect being the cause of hypocortisolism after long-term cortisol suppression.
Intellectual impairment after hyperthyroidism
Authors: Perrild Hans , Hansen Jens M. , Arnung Klaus , Olsen Poul Z. , Danielsen Ulla
Published: December 2008

Abstract. Electroencephalography (EEG) and neuropsychological tests empirically shown to be sensitive to diffuse cerebral damage were performed in 26 patients 10 years after successful treatment of hyperthyroidism and in a control group with non-toxic goitre. In the hyperthyroid state 81% had abnormal EEG before treatment, and 10 years after treatment 68% still had abnormal EEG compared with 41% in the control group (P < 0.05). In 7 out of 11 neuropsychological tests the previously hyperthyroid patients showed significant impairment compared with the control group. Twenty-three per cent of the patients displayed marked to severe intellectual impairment, 31% moderate and 41% slight or no impairment compared with 0%, 31% and 69%, respectively, in the control group (P < 0.05). Four patients had been granted disability pension on the basis of the intellectual dysfunction. Signs of intellectual impairment indicating irreversible brain dysfunction after thyrotoxicosis thus seem to be a frequent, although hitherto not generally recognized, finding.
Specific stimulatory effects of Graves' IgG on the release of triiodothyronine from the patients' own thyroids
Authors: Yamashita Shunichi , Izumi Motomori , Nagataki Shigenobu
Published: December 2008

Abstract. The present study was undertaken to investigate the release of thyroid hormones from cultured thyroid slices of untreated patients with Graves' disease in response to autologous IgG and IgG from other untreated patients with Graves' disease. Thyroid tissue (8–10 mg) was obtained by needle biopsy from 11 untreated patients with Graves' disease, and each biopsy was divided into 5 slices. Slices were then cultured in Ham's F-12 synthetic media for 7 days with IgG (1.3 mg/ml) obtained from the same patients, IgG obtained from other untreated patients, normal IgG, or bovine TSH (1.3 mIU/ml). Media were changed every day, and the concentrations of triiodothyronine (T3) in the media were measured by radioimmunoassay (RIA), and the concentrations of thyroidal cAMP were measured by radioimmunoassay on the last day of culture after incubation with 10 mm theophylline at 37°C for 30 min. When thyroid slices were incubated with autologous IgG, the release of T3 increased from the 3rd day, and the increase was 3- to 10-fold above controls on the 5th day, and the production of thyroidal cAMP significantly increased 2- to 3-fold. However, when slices were incubated with IgG obtained from other untreated patients, the concentration of T3 in media and the production of thyroidal cAMP did not differ from that in controls. TSH increased the release of T3 from thyroid slices 2.5-to 10-fold above controls on the 5th day and the production of cAMP 4- to 5-fold. These results strongly suggest that thyroid hormone releasing IgG in patients with Graves' disease are highly specific for autologous thyroids. The mechanism of this specificity may involve the role of self-recognition, such as antiidiotype antibody or anti-major histocompatibility complex antibody.
Inhibitory effects of antithyroid drugs on oxygen radical formation in human neutrophils
Authors: Imamura Minoru , Aoki Norihiko , Saito Takuya , Ohno Yasuhiro , Maruyama Yoshiyuki , Yamaguchi Junji , Yamamoto Toshio
Published: December 2008

Abstract. The effects of antithyroid drugs and related agents on human neutrophil function were studied. Neutrophil function was mainly assessed through oxygen radical formation as determined by chemiluminescence (CL) response, superoxide anion (O−2) generation and hydrogen peroxide production. Propylthiouracil (PTU) at a therapeutic concentration (10 μg/ml) inhibited CL response evoked by phorbol myristate acetate (PMA) and other stimulators. The inhibitory effect was not enhanced by pre-incubation of neutrophils with PTU and not exerted through a direct cytotoxic effect of the drug. It was not related to the kind of stimulators to evoke CL response in neutrophils either. However, the inhibitory effect disappeared when PTU was removed from the reaction mixture for CL response. PTU did not inhibit O−2 generation but markedly inhibited hydrogen peroxide production in neutrophils or activity of hydrogen peroxide in vitro. Morphologically, the unique change of cellular configuration of chemotactic neutrophils caused by N-formyl-methionylleucyl-phenylalanine (FMLP) was not influenced with PTU. Since hydrogen peroxide is mainly derived from O−2, these observations suggest that PTU may have a scavenger effect on hydrogen peroxide activity. Inhibition of CL response in neutrophils was also demonstrated with methimazole (MMI), thiouracil and thiourea, but not with imidazole and uracil, which suggests that their inhibitory effect on CL response in neutrophils may be closely related to the antithyroid activity.
Male pseudohermaphroditism due to 17β-hydroxysteroid dehydrogenase deficiency: gender reassignment in early infancy
Authors: Gross David J. , Landau Hedi , Kohn Gertrude , Farkas Amicur , Elrayyes Eyas , El-Shawwa Raghda , Lasch Eli E. , Rösler Ariel
Published: December 2008

Abstract. Male pseudohermaphroditism due to 17β-hydroxysteroid dehydrogenase (17β-HSD) deficiency has a high prevalence within the Arab population of the Gaza strip and is characterised by marked virilization at puberty, leading in many cases to the spontaneous adoption of a male gender role. As a result of this, parents of 7 affected male infants (aged 1– 10 months) born with female phenotype requested early gender reassignment. Diagnosis was suspected in 5 on the basis of a positive family history, but confirmed in all cases by the finding of low to normal testosterone levels (30–184 ng/dl) with high Δ4-androstenedione levels (188–808 ng/dl), after hCG. Treatment with im testosterone oenanthate (25–50 mg/dose) was given in one to three 3-months courses and penile size was increased into the normal range without evoking a significant increase in height velocity or skeletal maturation. Five patients underwent the first stage of male genitoplasty between 2 and 3 years of age. This consisted of bilateral orchidopexy, chordee release and penile lengthening – yielding finally an anatomically normal-sized and shaped penis.

Androgen responsive male pseudohermaphroditism due to 17β-HSD deficiency or a similar defect and diagnosed in infancy should be treated as soon as possible with systemic testosterone before considering any sex change, and in preparation for male genitoplasty. Early gender reassignment according to genetic and gonadal sex is probably the management of choice for these cases since this may result in a normal adjustment to the male gender role, particularly after puberty.
The local administration of relaxin induces changes in the microcirculation of the rat mesocaecum
Authors: Bigazzi M. , Del Mese A. , Petrucci F. , Casali R. , Novelli G. P.
Published: December 2008

Abstract. The clinical improvement of Reynaud's disease during pregnancy has been attributed to the increased relaxin (RLX) level in blood. Therefore we investigated the effect of topical porcine RLX (NIH-RXN-Pl) on the microcirculation of the mesocaecum of Wistar male rats, under direct microscope observation as judged by two observers. The hormone was applied locally to avoid systemic interferences either alone or after norepinephrine (NE) and promethazine (PM). The drugs were coded and the results were recorded independently by two observers. Porcine RLX induced rapid dilatation of the veins of the rat mesocaecum in a dose-related manner. The arteriolas and capillary flows were unchanged, while the venular flow was progressively reduced. The observed effects were sustained and disappeared with tissue wash-out. The RLX effects were reversed by addition of NE; conversely high doses of RLX were able to oppose the NE and PM vasospasm.

We conclude that the local administration of RLX influences the microcirculation, possibly through an action on the smooth muscle of the venulae. The effects seems antagonistic with those of NE and PM.
Hypothalamic defects in two adult patients with septo-optic dysplasia
Authors: Lam K. S. L. , Wang C. , Ma J. T. C. , Leung S. P. , Yeung R. T. T.
Published: December 2008

Abstract. Two adult patients with unilateral hypoplastic optic nerves, absent septa pellucida and hypopituitarism are described. Patient 1, aged 20, presented with diabetes insipidus due to partial vasopressin deficiency. Patients 2, aged 29, presented with focal epilepsy. Both had short stature. They showed absent growth hormone (GH) response to insulin-hypoglycaemia or glucagon, but responded to 100 μg growth hormone releasing factor (GRF-44) with a rise in circulating GH, suggesting a hypothalamic defect in GH release though a co-existing pituitary defect cannot be excluded. Other hypothalamic-pituitary functions were normal. These two patients probably represent the milder form of the clinical spectrum of septo-optic dysplasia which, with the extensive use of CT brain scans, will be increasingly encountered by physicians attending adult patients.
Effects of Acarbose on the relationship between changes in GIP and insulin responses to meals in normal subjects
Authors: Groop Per-Henrik , Groop Leif , Tötterman Karl Johan , Fyhrquist Frej
Published: December 2008

Abstract. The relationship between changes in gastric inhibitory polypeptide (GIP), C-peptide and insulin responses to meals was studied in 8 normal subjects after 2 weeks of Acarbose treatment. Acarbose caused a significant reduction of GIP and insulin responses (P <0.05). The decrease in insulin response could not be explained by changes in the glycaemic stimulus of insulin secretion, as Acarbose did not significantly change the plasma glucose response to meals during the study. The reduced insulin response was seen without a concomitant reduction in the C-peptide response to the meals, thus resulting in a decreased insulin/C-peptide ratio after Acarbose treatment (P < 0.05). The changes in GIP response after Acarbose correlated positively with the change in insulin/C-peptide ratio (r = 0.69; P < 0.05). Our data thus challenge the concept that Acarbose therapy affects the secretion of insulin. The positive relationship between changes in GIP response and changes in the insulin/C-peptide ratio rather suggests that GIP affects the metabolism of insulin or C-peptide.
Ontogenetic development of pancreatic thyrotropin-releasing hormone in human foetuses and in infants
Authors: Martino E. , Grasso S. , Bambini G. , Pardo G. , Vitti P. , Aghini-Lombardi F. , Pinchera A.
Published: December 2008

Abstract. The ontogeny of thyrotropin-releasing hormone (TRH) in pancreata of human foetuses from 15–36 weeks of gestation and of infants has been studied. TRH was detectable in the pancreas of a 15 week old foetus; a progressive increase of pancreatic TRH content was observed until the 34th week of gestation, whereas a progressive decrease was found in the late period of pregnancy and in 1 year old infants. In contrast, the pancreatic insulin content showed a progressive increase during the entire pregnancy and in the first year after birth. These data indicate that TRH and insulin have different ontogenetic patterns in the human pancreas.
Hormone levels in the foetal and neonatal prostate
Authors: Zondek T. , Mansfield M. D. , Attree S. L. , Zondek L. H.
Published: December 2008

Abstract. The prostates of 41 foetuses and neonates have been assayed for testosterone, 5α-dihydrotestosterone (DHT), oestradiol and oestriol and the presence of these hormones has been demonstrated in all cases. Oestriol was found to be present in the highest concentration. A highly significant correlation was found between testosterone and DHT as well as between DHT and oestradiol. The correlation between oestriol and oestradiol was also significant. It has been pointed out that the presence of these hormones is essential for the growth and development of the prostate gland.
Absorption of 1-deamino-8-D-arginine vasopressin from different regions of the gastrointestinal tract in rabbits
Authors: Lundin Stefan , Vilhardt Hans
Published: December 2008

Abstract. By using a specific radioimmunoassay for 1-deamino-8-D-arginine vasopressin (DDAVP), plasma concentrations were measured in rabbit plasma at various times after intra-gastrointestinal injections. Five anatomically distinct regions were employed to administer the peptide, namely: the stomach, the duodenum, the mid-part of the ileum, the ileo-coecal junction and the mid-part of the colon. In each case immunoreactive DDAVP could be demonstrated in plasma. The highest concentrations were observed after duodenal and ileocoecal administration. Absorption was rapid; peak levels were reached after 10–20 min.
Theophylline blunts the GH-response to growth hormone releasing hormone in normal subjects
Authors: Losa Marco , Huss Roland , König August , Müller O. Albrecht , von Werder Klaus
Published: December 2008

Abstract. Theophylline enhances GH-secretion in vitro, whereas in vivo a slight decrease of basal GH-levels has been observed. In the present study the effect of theophylline on the GH-responsiveness to acute and continuous administration of growth hormone releasing hormone (GHRH) was investigated. The following protocol was performed.

GHRH study. Fifty μg GHRH was given as an iv bolus followed by constant GHRH-infusion (100 μg/h) over 2 h after which another GHRH bolus of 50 μg was given.

GHRH plus theophylline study. GHRH was administered as in the first study and theophylline was infused at a constant rate of 3.56 mg/min over 3 h, starting one h before the GHRH bolus.

Theophylline study. Only saline and theophylline were infused.

GHRH alone led to a GH-rise within 30 min with a maximum of 22.8 ± 7.2 ng/ml (mean ± se) after which GH-levels decreased despite continuous GHRH-infusion to a nadir of 12.1 ± 4.4 ng/ml at 105 min. The second GHRH bolus led to a minimal GH-increase (13.3 ± 6.4 ng/ml at 135 min). Theophylline administration resulted in blunting of the GH-response to GHRH in all volunteers, with GH levels fluctuating between 4–6 ng/ml throughout GHRH-administration. Theophylline alone did not affect GH-levels in three subjects studied, whereas in the other one a GH secretory episode 90 min after administration of the drug was observed. Prl showed a minimal increase only after the second GHRH bolus (from 254.2 ± 7.7 μU/ml to 317.3 ± 96.0 μU/ml in study 1, and from 139.3 ± 26.9 μU/ml to 193.0 ± 32.6 μU/ml in study 2), TSH-levels did not change during any of the test-procedures and GHRH-levels were comparable in both study 1 and 2. Free fatty acids (FFA) rose progressively after theophylline administration (from 0.68 ± 0.10 mEq/l to 1.06 ± 0.08 mEq/l in study 2, and from 0.64 ± 0.12 mEq/l to 1.09 ± 0.05 mEq/l in study 3), but also after GHRH alone (from 0.50 ± 0.05 mEq/l to 0.78 ±0.11 mEq/l). This shows that therapeutical doses of theophylline blunt the GH-response to GHRH in normal subjects. The mechanisms involved may be a competition for the adenosine receptor at the pituitary, or an indirect effect mediated by the rise of FFA levels.