bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunochemical and biological characterization of calcitonin originating from transplanted medullary thyroid carcinoma in rats
Authors: Myhre Lisbeth , Ekeland Arne , Gautvik Kaare M.
Published: December 2008

The immunoreactive and biological activities of calcitonin (CT) produced by transplanted rat medullary thyroid carcinomas (MCT) have been studied. Immunoreactive CT (iCT) in serum and in MCT tissues of rats carrying tumours of generations 5–8 was characterized by gel filtration on Sephadex G-100 followed by radioimmunological measurements using region specific antiserum. The hypocalcaemic effect of sera and tumour extracts was tested in a rat bioassay.

Rats with transplanted MCT of the 5th and 6th generations had mainly (70–84%) circulating iCT species of molecular size comparable to intact hormone. However, in rats with tumours of the 7th and 8th generations corresponding circulating iCT forms comprised less than 52% of total immunoreactivity while 32–38% eluted earlier. In conparison, iCT corresponding to intact hormone represented 30–50% of total immunoreactivity in the tumour extracts and no differences were observed between the generations.

Subcutaneous injections of sera from MCT rats and of tumour extracts reduced the serum levels of ionized calcium in test rats. The sera containing mainly intact iCT showed the strongest biological potency.

We conclude that rat MCT transplanted under the kidney capsule is able to secrete biologically active CT. However, the heterogeneity of circulating iCT increases in rats with transplanted tumours of older generations, approaching the heterogeneity of stored hormone in the gland.
Effect of GIP on the secretion of insulin and somatostatin and the accumulation of cyclic AMP in vitro in the rat
Authors: Szecówka J. , Grill V. , Sandberg E. , Efendić S.
Published: December 2008

The effects of gastric inhibitory polypeptide (GIP) on insulin secretion as well as on the intra-islet accumulation of [3H]cyclic AMP were investigated in isolated pancreatic islets of the rat. In the presence of 6.7 mmol/l of glucose, 3.0 and 30 nmol/l of GIP induced both insulin and [3H]cyclic AMP responses, while lower and higher concentrations of the peptide were ineffective. A coupling of the two parameters was also found with regard to interaction between glucose and GIP. Thus while 30 nmol/l of GIP was stimulatory together with 6.7, 16.7 or 33.3 mmol/l of glucose, the peptide stimulated neither insulin release, nor the accumulation of [3H]cyclic AMP in the presence of a low concentration of glucose (3.3 mmol/l).

The concomittant release of insulin and somatostatin was studied in the perfused pancreas in order to assess a possible influence by somatostatin on the dose-response pattern for GIP-induced insulin release. In this preparation 1.0 to 10 nmol/l of GIP stimulated insulin and somatostatin secretion; however while these concentrations were equipotent on insulin release, 10 nmol/l of GIP stimulated somatostatin release more than 1 nmol/l, indicating differences in dose-reponse curves for the GIP-induced stimulation of the two hormones.

It is concluded that 1) modulation of GIP-induced insulin release is coupled to changes in cyclic AMP response in the islet, 2) GIP-induced somatostatin secretion may influence the concomittant insulin response.
Somatomedin production by rat liver in organ culture
Authors: Binoux Michel , Lassarre Claudine , Hardouin Nathalie
Published: December 2008

Radioligand assays have been used to study the production of insulin-like growth factor (IGF) and its carrier (IGFCP) by rat liver in organ culture. Bound IGF released into the culture medium was dissociated and separated from its carrier by gel filtration in 1 m acetic acid. IGF was measured by a competitive protein-binding assay using human IGF and the specific IGFCP produced by rat liver. IGF CP concentrations were assessed in terms of IGFCP binding to labelled IGF, compared to a reference IGFCP preparation obtained from rat serum.

Without added hormone,the ratios IGF:total protein and IGFCP:total protein in the culture media after 3 days' culture were approximately 7 and 70 times higher, respectively, than those in serum.

GH and insulin both stimulated IGF production. The response was dose-dependent, and significant at physiological concentrations of hormone (10 ng/ml GH and 10 μU/ml insulin. With 1 μg/ml GH and 1 mU/ml insulin, the IGF concentrations in the media on average reached 2½ times the base-line level. These hormones had no significant effect on IGF CP production.

One ng/ml cortisol stimulated IGF production, but, in response to increasing concentrations, there was a dose-dependent decrease in IGF production. By contrast, IGFCP production was stimulated and there was a positive correlation between the carrier concentration in the culture media and the amount of cortisol added.

The results indicate that insulin and cortisol, in addition to GH, have a direct influence on IGF production by the liver in vitro. They also suggest that the biosyntheses of IGF and its carrier are subject to different systems of regulation.
Observations on the effects of prolactin on LH-receptors and steroidogenesis in corpus luteum and testis of the hypophysectomized rat
Authors: van Straalen R. J. C. , Zeilmaker G. H.
Published: December 2008

In this study the effects of hypophysectomy and autotransplantation of the pituitary gland on the concentration of hCG-binding sites (LH-receptors) and steroidogenesis in the corpus luteum and the testis of the rat were investigated.

It was found that during pseudopregnancy both hCG-binding to homogenates of isolated corpora lutea and the progesterone levels in blood increase until day 7 and subsequently decrease until day 13. Hypophysectomy on day 5 led to a decrease of the number of LH-receptors and the serum progesterone level. By contrast hypophysectomy followed by autotransplantation of the pituitary gland increased the LH-receptor concentration and progesterone synthesis in spite of non-detectable LH-levels. Progesterone implants in hypophysectomized rats did not influence the number of LH-receptors. Hypophysectomy on day 0 without pituitary gland transplantation did not prevent the formation of some luteal LH-receptors measured on day 5 although progesterone was not secreted.

A similar effect of prolactin secreted by pituitary autografts on LH-receptors was seen in the testis. The rapid decline of the number of binding sites normally observed after hypophysectomy was prevented by the presence of two pituitary autografts. Testosterone and LH-levels were non-detectable in the operated male rats.

These data show that progesterone secretion by the corpora lutea is always associated with the presence of LH-receptors, regardless whether serum LH-levels are detectable or not. Moreover it appears that prolactin maintains or even increases the amount of LH-receptors in hypophysectomized male and female rats.
Thyroid hormone dependent nuclear proteins from rat liver
Authors: Rodriguez-Pena Angeles , Bernal Juan
Published: December 2008

Two nuclear proteins from rat liver were shown to be dependent on thyroid hormones. These proteins were present in the nucleosol or nucleoplasmic fraction, and were extracted from the nuclei with 0.15 m NaCl at pH8. After thyroidectomy, a 120 000-Mr polypeptide decreased in concentration to levels below 10% of normal control rats and another polypeptide of 81 000-Mr was increased. Treatment with T4 at physiological replacement doses for several days restored the levels of both proteins to normal. A single administration of 50 μg T3 induced a detectable increase of 120K after 14 h, with maximal effects at 48 h after administration. The minimum effective dose of T3 on 120K was 0.5 μg administered for three days. Preliminary observations suggest that the response of 81K to thyroid hormones is much more sensitive than that of 120K. The physiological role of these polypeptides is unknown, but they could be involved in the mode of T3 action at the nuclear level.
Biological activity of des-asp-,des-arg-angiotensin II in man
Authors: Kono Tsuyoshi , Ikeda Fumitake , Oseko Fumimaro , Ohmori Yoshiaki , Nakano Ryuichi , Muranaka Hideo , Taniguchi Ataru , Imura Hiroo , Khosla Mahesh C. , Bumpus F. Merlin
Published: December 2008

The biololgical activity of des-asp1-,des-arg2-angiotensin II (3-8AII) was studied in man. When 3-8AII was infused iv at rates of 22 and 308 pmol (17.5 and 250 ng)/kg · min separately into 5 normal men each for 120 min, blood pressure showed no change, plasma renin activity (PRA) decreased gradually and plasma aldosterone showed a gradual slight increase. The lower dose of 3-8AII partially inhibited captopril-induced PRA increase and plasma aldosterone decrease in the same 5 normal men and the higher dose of the hexapeptide completely abolished them. In one of the 5 normal men blood pressure rose in response to doses of 3-8AII greater than 2220 pmol (1750 ng)/kg · min. When 3-8AII was infused iv at 308 pmol/kg · min into 2 patients with Bartter's syndrome for 60 min, it caused marked decreases in PRA and plasma aldosterone but no change in blood pressure. This decrease in plasma aldosterone is thought to be secondary to the decrease in PRA. From these results it is evident that 3-8AII has a minimal pressor action, a weak aldosterone-stimulating action and a significant renin-suppressing action in man and this PRA-lowering action is thought to be due to direct inhibition of renin release by its whole molecule or a smaller part of the molecule.
Immunoreactive β-endorphin/lipotrophin in the chronically cannulated ovine foetus: response to bilateral foetal adrenalectomy
Authors: Hennessy D. P. , Hardy K. J. , Quigley M. E. , Wintour E. Marelyn , Yen S. S. C.
Published: December 2008

Adrenocorticotrophin (ACTH) is derived from a 'stem' hormone of approximately 31 000 daltons. In man, cleavage of this hormone can produce equimolar amounts of ACTH and β-lipotrophin (β-LPH) in the plasma. Further cleavage of β-LPH in either the pituitary or plasma can release β-endorphin (β-EP). The plasma concentrations of both ACTH and β-EP can be increased by stressful stimuli, adrenalectomy, pituitary-adrenal disorders, or decreased with glucocorticoid treatment.

This study investigated the presence of β-EP/LPH in the intact and adrenalectomized (adrX) ovine foetus. Three ovine foetuses were bilaterally adrX at the time of implantation of cannulae into the carotid artery and jugular vein (106–120 days gestation). The foetuses of 9 ewes were chronically cannulated (95–115 days gestation) to serve as controls. Gestation length was 147 ± 5 days. Plasma β-EP/LPH was measured using a heterologous modification of a human β-EP RIA. The assay system had molar cross-reactivity of about 20% with ovine β-LPH, thus results are expressed as β-EP/LPH-like immunoreactivity (IR-β-EP/LPH).

In the intact unstressed foetus the plasma IR-β-EP/LPH concentration was relatively constant throughout gestation 228.9 ± 12.0 pg/ml (mean ± sem, n = 35) except for the last 48 h prior to either parturition, abortion or in utero foetal death when concentrations were seen to rise to 357 ± 56.8 pg/ml (n = 10) in 5 out of 6 sheep. During gestation the IR-β-EP/LPH in amniotic fluid was less than in foetal plasma the mean being 130.5 ± 14.8 (n = 10). IR-β-EP/LPH in maternal plasma was similar to that in foetal plasma.

In the adrX foetus data has been arbitrarily divided into 3 age groups 90–121, 122–135 and > 136 days gestation, the IR-β-EP/LPH concentrations being 202.7 ± 16.3 (n = 9), 404.6 ± 54.8 (n = 13) and 2566 ± 681 (n = 5) pg/ml, respectively. The elevated IR-β-EP/LPH seen after 122 days does not appear to be reflected in either foetal urine or amniotic fluid. It can be suggested that the pituitary feedback systems controlling both IR-ACTH and IR-β-EP/LPH start to mature or change after 122 days gestation.

In summary these findings show the presence of an immunoassayable substance with β-EP/LPH-like reactivity in the plasma of the ovine foetus, and that this IR-β-EP/LPH can often increase prior to parturition, abortion of foetal death. After 122 days gestation IR-β-EP/LPH increases in adrX foetuses, suggesting that after this time feedback control systems with some product of the foetal adrenal first begin to appear.
Experimental induction of C cell tumours in thyroid by increased dietary content of vitamin D3
Authors: Thurston Valerie , Williams E. D.
Published: December 2008

Neonatal Wistar rats were given either 0, 5 or 10 μCi 131I within 24 h of birth. Following weaning, they were fed a diet high, normal or deficient in vitamin D, for up to 2 years. Animals were sacrificed at approximately 3 monthly intervals, and serial sections of thyroid scanned for C cell tumours following calcitonin localization. Plasma calcium levels were also measured, and all results statistically analyzed.

As expected, those animals given the high vitamin D had significantly raised calcium levels over those on a normal D diet, whilst those given a low D diet had lower calcium levels than normal.

Analysis of the incidence of C cell tumours showed that those given a high D diet had significantly more C cell tumours, whilst those on a low D diet had significantly fewer than normal. Radiation dose also influenced C cell tumour incidence.

There was a significant relationship between the vitamin D content of the diet and the incidence of C cell tumours, with those animals on a high D diet having the largest number of tumours. It is suggested that vitamin D or its metabolites may directly promote C cell growth, and that the high incidence of C cell tumours in the normal laboratory rat reflects the artificially high vitamin D content of the laboratory rat diet. The dietary vitamin D content may also be relevant to the variation in geographical incidence of medullary carcinoma in man. We consider it likely that vitamin D metabolites may play a significant role in the control of C cell function, hyperplasia and tumour formation in the rat, and that this may be more important in tumour formation than the role of serum calcium variation.
Durable remission of Cushing's disease after OP'DDD treatment
Authors: Couzinet Béatrice , Thomopoulos Pierre , Schaison Gilbert
Published: December 2008

A long-term remission of a case of Cushing's disease is described. The patient received medical therapy in the form of OP'DDD for 3 years without radiotherapy nor surgery. Clinical and laboratory remission was maintained for 7 years after discontinuation of drug therapy. In particular, a normal circadian rhythm of plasma cortisol and ACTH and normal suppressibility by low doses of dexamethasone were observed. The evolution of this case suggests that the most likely aetiology was a reversible hypothalamic disorder.
Evidence for two independent effects of oestradiol benzoate on the renin-angiotensin-aldosterone system
Authors: Kaulhausen Helmut , Weyand Cornelia
Published: December 2008

Plasma renin concentrations (PRC), plasma renin substrate concentration (PRS), plasma aldosterone and cortisol concentrations as well as plama renin activity (PRA) were measured in ovariectomized subjects after im administration of 10 mg oestradiol benzoate (EB).

The esterified oestrogen exerts two independent effects on the renin-angiotensin-aldosterone system.

1) 48 h after EB administration, PRS was significantly increased. Similar results were obtained for total plasma cortisol, reflecting transcortin concentration. In both cases, the increase was quantitatively related to the basal concentrations. These observations are consistent with the well known oestrogen-induced protein synthesis in the liver.

2) The elevation of PRC preceded that of PRS and was already significant 11 h after EB injection. The early rise in plasma renin activity was essentially caused by the increase in PRC, whereas an influence of the activated substrate synthesis was found later, between the 2nd and the 4th day post injection. The time course of plasma aldosterone concentration correlated well with the increased PRA.

The results provide evidence that EB has two different effects on the renin-aldosterone axis: an early one by elevating renin release and a delayed one by increasing renin substrate synthesis. Whereas the second mechanism can clearly be localized in the liver, extrarenal as well as direct renal effects of EB may be responsible for the renin stimulation.
Induction of ovulation in immature female rats by a single injection of 4-hydroxyoestradiol-dibenzoate
Authors: Emons Günter , Ball Peter
Published: December 2008

This study was designed to test the ability of 2- and 4-hydroxyoestrogens to induce ovulations and the formation of corpora lutea in immature female rats. To this end 25 day old animals received a single injection of different doses of either 4-hydroxyoestradiol-dibenzoate (10, 25, 50 μg) or 2-hydroxyoestradiol-dibenzoate (25, 250 μg) or oestradiol-benzoate (10, 25, 50 μg). On day 31 the ovaries were checked for corpora lutea.

4-Hydroxyoestradiol-dibenzoate and oestradiol-benzoate in doses of 50 or 25 μg significantly increased the number of animals with corpora lutea whereas animals treated with 10 μg of either steroid did not differ significantly from the respective vehicle groups. 2-Hydroxyoestradioldibenzoate, even at the high dose of 250 μg did not show a significant effect.

This is the first demonstration that a catecholoestrogen 4-hydroxyoestradiol - can induce ovulation. As its potency in doing so is similar to that of oestradiol and as 4-hydroxyoestradiol can be formed in neuroendocrine tissues from primary oestrogens, we conclude that this catecholoestrogen might play a role in the regulation of ovulation.
Stimulation of transport of alpha-aminoisobutyric acid into the testes of immature mice in vivo by follicle-stimulating hormone
Authors: Oza Nila , Meanock Sarah J. , Davies A. G.
Published: December 2008

Groups of immature mice were injected sc with radiocarbon-labelled alpha-aminoisobutyric acid (AIB) after being given a single sc injection of hFSH or of 0.9% saline. As an index of the transport of AIB, the specific activity of isotope was measured in homogenates of testis and of liver. FSH treatment caused statistically significant increases in the specific activity of isotope in the testes and in the ratio of testicular to liver specific activity. The effect was greatest in 9-day-old mice injected with FSH 16 h before removal of the testes. Uptake of labelled AIB was not stimulated after administration of hCG or testosterone. Doses of cycloheximide sufficient to reduce the rate of protein synthesis by over 99% did not impair testicular uptake of labelled AIB or the influence of FSH on AIB uptake. These results suggest that FSH stimulates amino acid transport into cells of the immature testis and that this action is independent of the stimulatory effect of FSH on testicular protein synthesis.
Urinary free and conjugated oestrone and oestradiol- 17β in early infancy
Authors: Kuhnle Ursula , Bidlingmaier Frank , Knorr Dietrich
Published: December 2008

Conjugated and free urinary oestrone and oestradiol-17β were determined by radioimmunoassay in 98 urine samples of 44 normal male and female infants ranging from 7 days to 2 years of age.

Both sexes excreted significantly more oestrone and oestradiol-17β during the first 3 months of life compared to the end of the first year. Values peaked at the beginning of the second month. During the first 7 months of life, female infants excreted significantly more conjugated oestradiol-17β than oestrone, whereas male infants consistently excreted equal amounts of conjugated oestradiol-17β and oestrone. However, both sexes excreted significantly more free unconjugated oestrone than oestradiol-17β during the same period.
Concentrations of 2-hydroxyoestrogens in human sera measured by a heterologous immunoassay with an 125I-labelled ligand
Authors: Berg D. , Thaler F. , Kuss E.
Published: December 2008

A heterologous immunoassay for 2-hydroxyoestrogens1 has been established in which antibodies raised against 2-hydroxyoestradiol-17-succinyl-BSA serve as binding protein and 2-hydroxyoestrone-17-cmo-[125I]iodohistamine as radioligand. Lipophilic serum components competing for binding sites in this system were defined as 'total 2-hydroxyoestrogens'. The underlying assumption of specificity was supported by the pattern of cross-reactivity evaluated with structural related steroids and o-diphenols and by the fact, that an additional chromatography of the serum extracts preceding the competing reaction had little if any effect. Sensitivity: 2.8 ± 1 pg/tube; accuracy: Y = 0.91x + 2.2; r = 0.989; precision: 5.8% intra-assay; 6.5% inter-assay. The following concentrations ( ± standard deviation) were found in the sera of healthy subjects.

Young men: 29 ± 5 pg/ml (n = 11); women follicular phase: 32 ± 8 pg/ml (n = 25); luteal phase: 53 ± 13 pg/ml (n = 23); postmenopausal women: 13 ± 4 pg/ml (n = 10); pregnant women 11th–20th week: 70 ± 16 mg/ml (n = 64); 36th–40th week: 240 ± 23 pg/ml (n = 40); newborn cord blood: 604 ± 43 pg/ml (n = 48).
Interrelationship between TSH- and prolactin secretion in patients with prolactinoma and autoimmune thyroiditis
Authors: Pelkonen Risto , Salmi J. , Lamberg B.-A.
Published: December 2008

The relationship between the TSH and prolactin (Prl) responses to TRH has been investigated in 36 patients with prolactinoma, in 12 patients with symptomless autoimmune thyroiditis (SAT) and in 10 patients with Graves' disease in remission (GD). Autoimmune thyroiditis in combination with prolactinoma was found in 3 patients. The TSH -response was exaggerated in 4 prolactinoma patients without autoimmune thyroiditis. Moreover, in the patients with prolactinoma and intact function of the non-tumours pituitary gland the mean TSH increment was higher than in the controls. In patients with SAT, on the other hand, the Prl-response to TRH was significantly greater than that in the controls and in patients with GD.

The significance of these findings is not obvious but they suggest that TRH may be involved in the development of prolactin secreting adenomata.
Pituitary prolactinoma, adrenal aldosterone-producing adenomas, gastric schwannoma and colonic polyadenomas: a possible variant of multiple endocrine neoplasia (MEN) type I
Authors: Doumith Roland , de Gennes Jean Luc , Cabane Jean Paul , Zygelman Nicole
Published: December 2008

A large pituitary prolactinoma was found in a mentally deficient 45 year old woman presenting with amenorrhoea, glactorrhoea, headache, anaemia and hypertension, and removed surgically. She was subsequently found to have multiple adrenal aldosterone-producing adenomas, a gastric schwannoma and colonic polyadenomas. All these tumours were also removed surgically. Despite the absence of parathyroid and islet-cell hyperplasia, this case seems to be a variant of multiple endocrine neoplasia (MEN) type I.
Effects of glucocorticoid on body growth and serum levels of somatomedin A in the rat
Authors: Asakawa Kumiko , Takano Kazue , Kogawa Megumi , Hasumi Yoko , Shizume Kazuo
Published: December 2008

Serum levels of somatomedin A, as measured by radioreceptor assay, and body weight gain were 86.5 ± 9.2% and 166.9 ± 7.8% (N = 5) of the initial values, respectively, after 18 days administration of 2.5 mg cortisone acetate (CA). These values were significantly lower than those for saline treated rats (P < 0.005). Reduced serum somatomedin A and body growth rate were partially restored after halting the injection of CA.

Combined administration of daily doses of 100 μg hGH with CA did not prevent the decrease in somatomedin activity in treated rats. This observation suggests that GH plays a minor (or no) role in the fall of serum somatomedin A in CA-treated rats.

From these data we conclude that glucocorticoids reduce serum somatomedin by inhibiting the effect of GH on the generation of somatomedin.
Vasopressin in the cerebrospinal fluid of patients with normal pressure hydrocephalus and benign intracranial hypertension
Authors: Hammer Mogens , Sørensen Per Soelberg , Gjerris Flemming , Larsen Kim
Published: December 2008

We have studied plasma and cerebrospinal fluid vasopressin (CSF-AVP) and osmolality in 28 patients with cervical or lumbar pain syndromes (control patients), 11 patients with normal pressure hydrocephalus (NPH) and in 5 patients with benign intracranial hypertension (BIH). Vasopressin concentration in lumbar CSF to a high extent reflected the actual ventricular CSF-AVP concentration. In all groups CSF-AVP was lower than plasma AVP. Mean CSF-AVP in the control group was 1.3 pg/ml ± 0.1 (sem). In the NPH patients, who all suffered from severe dementia, CSF-AVP level was not different from that found in the control group (1.4 pg/ml ± 0.2). In contrast to the findings in the two other groups CSF osmolality in BIH patients was higher than plasma osmolality (P < 0.02). CSF-AVP in the BIH patients, characterized by an elevated intracranial pressure (ICP), was higher than in the control group (2.7 pg/ml ± 0.4, P < 0.001).
Early remission in thyrotoxicosis produced by short courses of treatment
Authors: Bing R. F. , Rosenthal F. D.
Published: December 2008

Twenty-eight patients with Graves' disease were treated with short-term antithyroid drug therapy, i.e. treatment was discountinued as soon as they became euthyroid. This was less than 4 months in all patients. Ten patients remained euthyroid, although in two of these, thyrotoxicosis recurred after the patients had been euthyroid for more than 12 months. The other 18 patients relapsed within 12 weeks of stopping therapy, and only two have become euthyroid after a further 12 month period of treatment. All patients who remitted were thyrotoxic for the first time whereas all patients with a past history of thyroid disease relapsed. Positive thyroid microsomal antibody titres were more frequent in patients who remitted, otherwise there were no indicators of a favourable outcome.

The remission rate with antithyroid therapy which is only continued until the patient becomes euthyroid is similar to that for treatment lasting 12–18 months. Short-term therapy has the advantage of savings in both patient and clinician time.
Responses to TRH, T3 suppression tests and histological findings by needle biopsy in patients with simple goitre in Japan
Authors: Fukino Osamu , Tamai Hajime , Kumai Mitsuharu , Ohsako Noriyuki , Kuma Kanji , Nagataki Shigenobu
Published: December 2008

Studies were performed in 120 patients with simple goitre, defined as relatively soft diffuse goitre. All were clinically and biochemically euthyroid and their antithyroid antibodies were negative. The TRH test was performed in 115, and a T3 suppression test was performed in 99 after the TRH test, while satisfactory biopsies of the thyroid were obtained in 37. The results showed that 28 of the 115 cases (24%) had an abnormal response to TRH; 8 (7%) were hyporesponders and 20 (17%) were hyperresponders. The T3 suppression test showed that 3 of 99 cases (3%) were non-suppressible. As determined by histological examination of the needle biopsy specimen, 17 of the 37 cases (46%) had normal follicles without lymphocytic infiltration, 10 (27%) had diffuse chronic thyroiditis, 5 (14%) had focal thyroiditis and 4 (11%) had diffuse epithelial hyperplastic change, and 1 (3%) had an adenomatous goitre.

It is suggested that simple goitre defined as above includes various thyroid diseases and that the results of TRH tests, antithyroid antibody estimations and histological findings do not correlate in many patients.
Defects in intrathyroidal binding of iodine and the perchlorate discharge test
Authors: Hilditch T. E. , Horton P. W. , McCruden D. C. , Young R. E. , Alexander W. D.
Published: December 2008

The kinetics of [123I]iodide uptake were studied when organification of iodine by the thyroid gland was normal and when this binding function was diminished by drugs or disease. Each study was terminated by a sodium perchlorate discharge test (300–600 mg iv) at 60 min or, in some cases, 10–30 min. The results confirmed that binding takes place rapidly in the uninhibited gland with the binding rate constant being at least 0.150 min−1. Discharge from the uninhibited gland is less than 3.5% of the gland uptake when perchlorate is given 60 min after the radioiodide. Subjects with an intrinsic binding defect manifested discharges of 11% or greater of the 60 min uptake and the estimated binding rate constants ranged from 0.003–0.057 min−1. Thyrotoxic subjects receiving 5 mg carbimazole twice daily manifested discharges ranging from 5.4–64.2%, and in those receiving 20 mg twice daily the observed discharges were 67.6–94.6% of the 60 min uptake.

The study shows that a correctly performed perchlorate discharge test will detect minimal inhibition of iodine binding. An important factor is the duration of the follow-up period after perchlorate is given. In some of the cases studied discharge was not complete until 60 min after the perchlorate.
In vitro lymphocyte proliferation in response to polyclonal activators and microbial antigens, and production of immunoglobulins stimulating thyroid adenylate cyclase in Graves' disease
Authors: Bech Karine , Andersen Vagn , Madsen Stig Nistrup
Published: December 2008

Cultures of blood lymphocytes from 16 patients with Graves' disease (GD) and 14 matched controls were studied. Incorporation of [14C]thymidine was significantly increased in unstimulated cultures of GD lymphocytes, while the incorporation after stimulation with polyclonal activators (concanavalin A, pokeweed mitogen, phytohaemagglutinin), microbial antigens (E. coli, Candida albicans extract, purified protein derivative of tuberculin, Yersinia enterocolitica serotype 3) and subcellular fractions of human thyroid antigens did not differ from the controls. Due to the increased incorporation in unstimulated cultures, stimulation index is not suitable as an indicator of lymphocyte sensitization. After polyclonal activation or stimulation with thyroid antigens the lymphocytes were cultured for up to 21 days, and the supernatants were investigated for thyroid adenylate cyclase stimulating immunoglobulins (TACSI). No TACSI were demonstrated in supernatants of the lymphocyte cultures neither after polyclonal activation nor after specific stimulation with several thyroid antigens.
Growth hormone, prolactin and cortisol nyctohemeral variations during naloxone-induced opiate receptor blockade in man
Authors: Delitala G. , Giusti M. , Rodriguez G. , Mazzocchi G. , Ferrini S. , Baccelliere L. , Montano V. , Rosadini G. , Giordano G.
Published: December 2008

To evaluate the role of endogenous opioid peptides in prolactin (Prl), growth hormone (GH) and cortisol neuroregulation, 50 mg of the opiate antagonist naloxone was infused over 24 h to 6 normal male volunteers. An additional naloxone dose (5 mg) was given iv as a bolus injection at 20.00 h. Blood specimens were collected hourly by means of a portable constant withdrawal pump.

Naloxone failed to alter 24 h secretion of GH and Prl. The sleep-related GH and Prl rise was also unaffected by the opiate blocker. Moreover, naloxone failed to alter the circadian rhythm of cortisol and its 24 h concentration.

The results do not suggest a major role of opiate receptors in spontaneous GH, Prl and cortisol secretion in man.
Immunological and clinical characterization of patients with untreated euthyroid and hypothyroid autoimmune thyroiditis. Antibody spectrum, response to TRH and clinical study
Authors: Scherbaum W. A. , Stöckle G. , Wichmann J. , Berg P. A.
Published: December 2008

In a region of endemic goitres, 200 untreated patients in whom thyroid microsomal (MCHA) and/or thyroglobulin (TGHA) antibodies have been detected were analyzed and other organ specific autoantibodies were tested. Thyroid function was assessed by a TRH test in all of them. Patients with previous thyroid disease and patients with clinical or biochemical signs of thyrotoxicosis were excluded.

In 58 (29%) of the patients diseases coexisted in which a high incidence of autoimmune reactions has been recognized. In the absence of the corresponding clinical disease, 13.7% of the patients had antibodies to parietal cells of the stomach, 3.1% had antibodies to adrenal cortex, 1% to steroid producing gonadal cells, 1% to pancreatic islet cells, and 0.5% of the patients had antibodies to striated muscle fibrils. The incidence of associated organ-specific autoantibodies was no higher in patients with hypothyroidism (36.4%) compared with patients who had a normal thyroid function (27.9%). The determination of a 'significant' thyroid antibody titre is discussed.

In 24.5% of the 200 patients a form of hypothyroidism was recognized. Fifty of the patients with TGHA titres ≥ 6400, and 56.2% of those with MCHA ≥ 102400 were hypothyroid. Patients with such titres of thyroid antibodies should be examined and followed up. Patients with associated islet cell or adrenal antibodies should be reinvestigated and followed up observing their glucose tolerance and adrenocortical function, respectively.
Plasma testosterone and androstenedione in insulin dependent patients at time of diagnosis and during the first year of insulin treatment
Authors: Gluud Christian , Madsbad Sten , Krarup Thure , Bennett Paul
Published: December 2008

Ten male patients and 6 female patients with newly diagnosed insulin dependent diabetes mellitus and significant ketosis were studied before and during the first year of insulin treatment. At onset plasma concentrations of testosterone and androstenedione were significantly (P < 0.02) decreased in female patients when compared to healthy sex- and age-matched controls. Plasma concentrations of testosterone and androstenedione increased significantly (P < 0.001 and P < 0.05) in both sexes during insulin therapy. Plasma concentrations of testosterone were not significantly different from controls in both sexes after 4 days of insulin treatment and remained so during the first year of insulin treatment. Plasma concentrations of androstenedione were not significantly different from controls in both sexes after 4 days of insulin treatment, but increased to levels significantly raised in both males (P < 0.001) and females (P < 0.05) after 7 days and during the first year of insulin treatment.
Pituitary responses to a dopamine antagonist at different times of the day in normal women
Authors: Pérez-López F. R. , González-Moreno C. M. , Abós M. D. , Andonegui J. A. , Corvo R. H.
Published: December 2008

In order to determine whether or not pituitary responsiveness to the dopaminergic antagonist clebopride changes during the nyctohemeral cycle, 10 healthy women with regular cycles were given 1 mg of clebopride orally at 09.00 h and 24.00 h with at least a 5 day interval between each test. In addition, 5 of the women were given a placebo instead of clebopride at midnight to evaluate the spontaneous hormonal changes. During the 24.00 h test the women had significantly higher P < 0.05) mean TSH basal levels. Serum prolactin (Prl) increased significantly (P < 0.001) after clebopride administration while these changes did not occur when placebo was used instead of clebopride at midnight. The Prl response to clebopride was qualitatively similar at 09.00 h and at 24.00 h. Clebopride given at midnight induced a significant increase (P < 0.05) in serum TSH while this change did not occur when the drug was given at 09.00 h or when placebo was given at midnight. The administration of clebopride resulted in no discernible alterations in serum LH, FSH or GH in either the 09.00 h or the 24.00 h tests.

Thus, Prl responses to clebopride were similar in the morning and at midnight, TSH significantly increased after clebopride at midnight whereas this did not occur when the drug was given in the morning, and no significant changes were induced in LH, FSH or GH at the times studied.
Long-term effect of oestrogens in combination with gestagen on plasma prolactin and FSH levels in post-menopausal women
Authors: Hagen Claus , Christiansen Claus , Christensen Merete Sanvig , Transbøl Ib
Published: December 2008

Plasma prolactin (Prl) and follicle stimulating hormone (FSH) concentrations were determined in 196 normal post-menopausal women, aged 45–54 years, receiving different doses of oestrogens in combination with gestagen (28 day cycle) in a placebo-controlled trial. In experiment I, 15 women received trisequens forte for 3 years, 19 women the same hormone combination for 2 years followed by 1 year's placebo treatment, and 15 women received placebo for 3 years. In experiment II, 30 women received trisequens forte, 22 women trisequens, 23 women trisequens mite, 20 women trisequens without oestriol, and 42 women placebo for 1 year. In both studies plasma concentrations of Prl and FSH were measured with 3 to 6 months interval.

The mean plasma Prl concentration increased about 25% (P < 0.01) in all hormone treated groups in both experiments within 1 year's treatment. However, only 26/139 (19%) of the hormone treated women had elevated Prl levels (> 20 μg/l) after 1 year of treatment. The elevated mean plasma Prl levels were maintained throughout the second and the third year of treatment with a trend to further increase. Initially, 6/196 (3.1%) of the post-menopausal women had plasma Prl concentrations of 21–40 μg/l. After 3 years of hormone therapy, 5/15 (33%) had plasma Prl concentrations of 21–60 μg/l. A significant and clearly dose-related fall in the plasma FSH concentration occurred in the hormone treated groups. The decrease varied between 40% and 75% and was seen within the first 3 months of treatment. No significant changes occurred in the mean plasma concentrations of FSH and Prl in the placebo groups.

It is concluded that hormone substitution with cyclical oestrogen/gestagen induces a rise in plasma Prl concentration, which is not related to the dose of oestrogens; and a fall in plasma FSH concentration, which is doserelated. Furthermore, it is suggested that oestriol has no significant Prl stimulating effect.
The effect of ageing on insulin sensitivity and insulin secretion in non-obese healthy subjects
Authors: Ratzmann K. P. , Witt S. , Heinke P. , Schulz B.
Published: December 2008

The relationship of age to insulin sensitivity was studied in 74 non-obese healthy subjects with normal fasting plasma glucose concentration, ranging in age from 17 to 65 years. Glucose tolerance and early as well as late insulin responses were characterized by means of a 2 h glucose infusion test (12 mg/kg/min) primed by an initial injection of 0.33 g/kg body weight glucose. Glucose tolerance did not markedly differ between young (< 30 years; n = 31) and middle-aged subjects (31–45 years; n = 29) but deteriorated significantly in the elder group (> 45 years; n = 14). Early and late insulin responses to glucose were not appreciably altered during ageing in this selected healthy population. For the determination of insulin sensitivity a 1 h priming dose-constant infusion technique (two 30 min periods of 8 and 16 mU/kg, insulin 'MC-Actrapid', initiated by a start injection of 1 and 2 mU/kg, respectively) was used. The percent decrease of plasma glucose, FFA and glycerol levels serves as a measure of the whole body sensitivity to exogenous insulin. Under condition of identical steady-state insulin levels the decrease in plasma glucose was significantly reduced in elderly (24 ± 5%) vs young (34 ± 2%) subjects (P < 0.05). However, a marked sensitivity to the antilipolytic effect of insulin was demonstrated in elderly subjects considered to be resistant to its glucose-lowering action. There was no evidence that disappeared time and metabolic clearance rate of insulin were altered with advancing age. In conclusion, the impaired insulin sensitivity to glucose metabolism seems to be the primary factor responsible for the deterioration of glucose tolerance with advancing age.
Early detection of patients at risk of developing diabetic nephropathy. A longitudinal study of urinary albumin excretion
Authors: Parving H.-H. , Oxenbøll B. , Svendsen P. Aa. , Christiansen J. Sandahl , Andersen A. R.
Published: December 2008

In an attempt to detect patients at high risk of developing diabetic nephropathy, a longitudinal study of urinary albumin excretion rate (radial immunodiffusion) was carried out in 15 female and 8 male long-term insulin-dependent diabetics without proteinuria (negative Albustix test).

Five females and 3 males had an elevated urinary albumin excretion at the time of screening, mean 115 ± 26 (sd) mg/24 h. Our upper normal range for urinary albumin excretion is ≤ 40 mg/24 h. The 5 patients with the highest albumin excretion subsequently developed persistent albuminuria, 132 → 1007 mg/24 h, P < 0.05, elevated serum creatinine, 83 → 128 μmol/l, P < 0.05, and raised blood pressure, 135/86 → 163/112 mmHg, P < 0.05. One patient developed intermittent albuminuria (positive Albustix test), while the variables in the remaining 2 patients were about the same during the 6 years observation period. Fifteen patients had a normal urinary albumin excretion, mean 17 ± 9 (sd) mg/24 h, at the time of the screening. Intermittent and persistent albuminuria developed in 2 patients, while albumin excretion, serum creatinine, and blood pressure were nearly unchanged in the remaining 13 patients after 6 years.

Our longitudinal study indicates that early detection of patients at high and low risk of developing persistent proteinuria i.e. diabetic nephropathy, is possible by using a sensitive method for measuring urinary albumin excretion.
Effects of diets rich and poor in fibres on the development of hereditary diabetes in mice
Authors: Berglund Ove , Hallmans Göran , Nygren Charlotte , Täljedal Inge-Bert
Published: December 2008

Young mice with different genetic dispositions to obesity and hyperglycaemia were fed isocaloric diets rich (B-diet) or poor (O-diet) in fibre from rye. Normal C57BL/KsJ-+/+-mice developed equally well on the two diets with no differences in serum glucose or insulin. In non-inbred ob/ob-mice both diets were as effective as standard laboratory diet in supporting the fat accumulation and weight gain typical of these animals. No effect on serum insulin was observed, but at the age of 10 and 13 weeks the ob/ob-mice were more hyperglycaemic on the O-diet than on the B-diet. C57BL/KsJ-db/db-mice on the B-diet developed and maintained obesity until 20–25 weeks of age; they then began to lose weight and died at a median age of 36 weeks. KsJ-db/db-mice on the O-diet soon began to mobilize their fat reserves and died at a median age of 28 weeks; they also exhibited a more severe hyperglycaemia and less pronounced hyperinsulinaemia than KsJ-db/db-mice fed the B-diet. It is concluded that, at least in mice, the manifestations of a defined genetic disposition to severe diabetes mellitus can be modified by such simple an environmental factor as rye bran.
Acromegaly and hypertension: role of the renin-angiotensin-aldosterone system
Authors: Karlberg Bengt E. , Ottosson Anna-Maria
Published: December 2008

The incidence of arterial hypertension was evaluated in a partly retrospective study of patients with active acromegaly.

Of 37 patients studied, 18 (48%) had hypertension, i.e. a supine blood pressure of > 160/95 mmHg. The type of hypertension was explored further by measuring plasma renin activity and, in some patients plasma aldosterone concentrations before and after stimulation (upright posture or furosemide 80 mg given orally). Urinary 24 h excretion of aldosterone was also determined.

About half of the patients with hypertension but also a substantial part of normotensive acromegalics had inappropriately low plasma renin levels both during basal conditions and after stimulation. On the other hand urinary aldosterone excretion was either normal or (in 2 patients) slightly elevated. There was no other evidence of coexistent primary aldosteronism.

Our results confirm previous reports of a high frequency of alterations in the renin-angiotensin-aldosterone system in acromegalic patients with growth hormone excess which in some instances may lead to an elevated blood pressure. The biochemical changes have many similarities to low renin essential hypertension.

A volume factor may be operating in acromegalic patients with hypertension since in 10 patients treatment with the aldosterone antagonist, spironolactone, with doses between 50–200 mg daily lowered blood pressure to near normal levels. Thus, spironolactone seems to be a worthwhile alternative in the treatment of hypertensive acromegalics.
Plasma progesterone levels following subdermal implantation of progesterone pellets in lactating women
Authors: Croxatto Horacio B. , Díaz Soledad , Peralta Octavio , Salvatierra Ana María , Brandeis Astrid
Published: December 2008

The magnitude and duration of elevated plasma progesterone levels resulting from subdermal implantation of progesterone pellets were investigated in full nursing women. This condition was chosen because it is associated with a low rate of ovulation and minimal endogenous progesterone production. In addition, treatment with progesterone pellets was intended to be a substitute for oral or parenteral administration of synthetic progestogens to nursing mothers. A control group of full nursing women receiving no hormones provided blood samples so that basal plasma progesterone levels from the second to the sixth post-partum month could be assessed. Progesterone pellets were implanted subdermally on day 30–35 after delivery. Insertion of 2, 4 or 6 pellets each containing 100 mg of progesterone caused an initial elevation of plasma progesterone to 5.9, 9.9 and 13.5 nmol/l, respectively. This initial elevation was followed by a gradual decline, so that basal levels were attained at 70, 100 and 150 days after insertion of 2, 4 or 6 pellets.

Implantation of 6 progesterone pellets led to a significant decrease in the ovulation rate of nursing women. These results indicate that subdermal implantation of 6 progesterone pellets can provide biologically effective levels of the hormone for up to 5 months.
Immunocytochemical study of the hypophysis in 25 dogs with pituitary-dependent hyperadrenocorticism
Authors: Peterson Mark E. , Krieger Dorothy T. , Drucker William D. , Halmi Nicholas S.
Published: December 2008

Pituitary adenomas were found in 21 (84%) of 25 dogs with spontaneous pituitary-dependent hyperadrenocorticism. Six dogs had pars intermedia adenomas, whereas 15 had tumours of the pars distalis. Diffuse corticotroph cell hyperplasia was found in 1 of the 4 pituitaries without adenoma; in 2 dogs with pituitary adenoma, coexisting hyperplasia of the surrounding corticotrophs was also present.

Immunocytochemical staining of the pituitaries revealed positive staining for ACTH, β-lipotrophin, and β-endorphin in the majority of both pars distalis and pars intermedia adenomas. The most frequent and intense staining was found with anti-β-endorphin. In most part intermedia tumours, many cells stained strongly for α-MSH; double immunostaining of one pars intermedia adenoma for ACTH and α-MSH showed that some tumour cells stained only for ACTH or α-MSH whereas others contained both peptides. Only occasional cells stained for α-MSH in pars distalis adenomas.