bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of short-lasting atrial pacing on the release of atrial natriuretic peptide, vasopressin, and methionine enkephalin in man
Authors: Ota Kozo , Kimura Tokihisa , Ito Meiichi , Inoue Minoru , Shoji Masaru , Shinoda Susumu , Nagashima Michio , Matsui Kuniaki , Iitake Kazuhiro , Yoshinaga Kaoru
Published: December 2008

Abstract. In order to study the effect of atrial tachycardia on the release of atrial natriuretic peptide (ANP), AVP, and methionine enkephalin (M-Enk), plasma concentrations of these peptides in the right ventricle were determined in patients with various arrhythmias (N = 10) during cardiac catheterization and incremental atrial pacing. Each pacing (100 per min, the maximum rate for 1:1 atrioventricular conduction, and 200 per min) lasted 4 to 5 min. Plasma ANP was significantly increased from 53.1 ± 12.2 in the resting condition to 168.9 ± 59.9 pmol/l at a pacing rate of 200 beats per min (P < 0.05); plasma AVP tended to decrease, but not significantly, and plasma M-Enk did not change at all. Pulse pressure in the right atrium (PPRA) and mean right atrial pressure (MRAP) tended to increase during the pacing, and at the rate of 200 beats per min PPRA was significantly higher than at the rate of 100 beats per min. Mean arterial blood pressure, plasma osmolality, and plasma sodium and potassium concentrations did not change significantly. There were significant correlations between plasma ANP and PPRA, MRAP and heart rate. These results indicate that atrial pacing stimulates ANP release with a rise in right atrial pressure, but does not influence M-Enk and AVP releases.
Gonadal function in male offspring of pinealectomized female rats
Authors: Jarrige J. F. , Tlemcani O. , Boucher D.
Published: December 2008

Abstract. Female rats were exposed to a short (6 L: 18 D) photoperiod from 21 days of age. On day 2 of gestation, animals were pinealectomized or sham-operated. Lighting regimens were not changed during the course of the study. Male offspring of the 2 groups of rats were sacrificed on days 30, 42 and 49 after birth. Pinealectomy of the mother induced the following modifications: in 30-day-old offsprings, a decrease in prostatic weight and plasma dihydrotestosterone level; in 42-day-old rats, a decrease in prostatic weight, in testicular androstenedione and dihydrotestosterone content, and in plasma testosterone and dihydrotestosterone levels; in 49-day-old animals, decreased testicular and plasma testosterone and dihydrotestosterone levels. These results indicate that rat testicular function, after exposure to a short photoperiod beginning before conception, is decreased by maternal pinealectomy. The mother's pineal gland may play a part in the control of rat testicular function.
The rapid diagnosis of sensitivity or resistance to dopamine agonists with depot bromocriptine
Authors: Grossman A. , Wass J. A. H. , Besser M.
Published: December 2008

Abstract. Some patients with hyperprolactinaemia are unable to tolerate even low doses of oral bromocriptine. In such cases, it is difficult to predict whether serum prolactin might be normalized if higher doses could be tolerated, or whether true resistance to bromocriptine is present. We have investigated 8 such patients who were subjected to a dopamine infusion (4 μg/kg per min for 4 h), followed by an injection of 50 mg of depot bromocriptine on a separate occasion. Serum prolactin was normalized in 4 patients during dopamine, and in 6 patients 12–48 h following depot bromocriptine. The 2 patients who failed to respond to depot bromocriptine also failed to respond to high oral doses of bromocriptine, while the remaining 6 patients were successfully transferred to oral bromocriptine without adverse reactions after the depot preparation was administered, and with a normalization of serum prolactin. It is concluded that depot bromocriptine may represent a better predictor of true unresponsiveness to dopamine agonist therapy than a dopamine infusion, and may also allow for initiation onto oral therapy of previously intolerant patients.
Effects of two novel dopaminergic drugs, CV 205-502 and CQP 201-403, on prolactin and growth hormone secretion by human pituitary tumours in vitro
Authors: Venetikou Maria S. , Burrin Jacky M. , Woods Christine A. , Yeo Tom H. , Brownell Judith , Adams Eric F.
Published: December 2008

Abstract. Two novel dopaminergic drugs, designated CV 205-502 and CQP 201-403 have recently been developed by Sandoz Pharmaceuticals Ltd (Basle, Switzerland). The effects of these drugs on PRL and GH secretion by normal rat and tumorous human pituitary cells in vitro have been investigated. Low doses of both CV 205-502 and CQP 201-403 immediately and profoundly suppressed PRL secretion, which failed to recover up to 7 h after removal of the drugs. Similarly, CQP 201-403 significantly suppressed basal GH secretion by human pituitary somatotropic tumours in culture, and both drugs significantly reduced the stimulatory effect of GHRH. These effects are more potent and longer acting than the previously described in vitro effects of bromocriptine. It is concluded that CV 205502 and CQP 201-403 hold potential for the treatment of patients with hyperprolactinaemia and, possibly, also in patients with acromegaly.
Evidence for a physiological reduction in brain dopamine but not norepinephrine metabolism during the preovulatory phase in normal women
Authors: Paradisi Roberto , Grossi Gabriele , Venturoli Stefano , Capelli Maurizio , Magrini Otello , Porcu Eleonora , Pasquali Renato , Flamigni Carlo
Published: December 2008

Abstract. To investigate the role of brain catecholamine (CA) activity in the mechanisms related to physiological ovulatory function, we used high-performance liquid chromatography with electrochemical detector to measure the levels of urinary dopamine (DA), norepinephrine (NE), epinephrine (E), vanillylmandelic acid (VMA), homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), and total 3-methoxy-4-hydroxy-phenylglycol (MHPG) in a group of 12 normal women during both the early follicular and pre-ovulatory phases of the menstrual cycle. The mean (± sem) concentrations of HVA and DOPAC were significantly lower (P < 0.001) during the pre-ovulatory phase than during the early follicular phase, whereas those of DA, NE, E, VMA and total MHPG were unaltered. A significant negative correlation between urinary HVA and plasma LH (r = −0.70, P < 0.01) was also found during the pre-ovulatory period, whereas no significant negative correlations were found between urinary HVA and plasma PRL, progesterone and oestradiol. These data show: 1) reduced brain DA activity and 2) unchanged brain NE activity at the time of the midcycle surge in normal women, suggesting a physiological variation of the central DA metabolism in ovulatory function.
Role of renal catecholamines in the control of sodium and water excretion: lack of natriuresis by endogenous dopamine in the rat kidney
Authors: Sato Tamotu , Minami Satoshi , Okabe Takashi , Igarashi Noboru
Published: December 2008

Abstract. The physiological role of dopamine in renal Na and water excretion was studied in rats treated with L-3,4-dihydroxyphenylalanine (L-DOPA), haloperidol or 6-hydroxydopamine for 1 week. Daily-pooled urine samples, plasma, and kidneys were obtained from the experimental groups and untreated controls. Urinary dopamine was markedly elevated in L-DOPA-treated and transiently decreased in haloperidol-treated rats. Urinary epinephrine, but not norepinephrine was increased in the L-DOPA and haloperidol groups. However, there was no significant difference in urine volume, urinary Na, urinary K, plasma Na and K levels between the experimental groups and controls, except for 6-hydroxydopamine-treated rats. They showed a definite increase in urinary volume, Na, K and aldosterone excretion, whereas the renal norepinephrine and epinephrine content was reduced. Urinary cAMP and Na-K ATPase activity were also similar in all groups, whereas renal cAMP content and aromatic amino acid decarboxylase activity were significantly increased in the L-DOPA and haloperidol groups, suggesting an activated catecholamine synthesis in the kidney. [3H]haloperidol binding was also increased by the L-DOPA and 6-hydroxydopamine administration, but the half maximal displacement dose was similar in all groups (6.4 × 10−9 mol/l), indicating an increase in the number of dopamine binding sites. These results indicate that 1) in contrast to the pharmacological effect of dopamine, locally-formed dopamine has no direct natriuretic action in the kidney; 2) an enhanced production of dopamine in the kidney does not suppress aldosterone secretion, and 3) renal norepinephrine and/or epinephrine play a significant role in Na retention. In conclusion, endogenous dopamine is unlikely directly to control Na and water excretion in the kidney.
Handling of iodothyronines by the liver and kidney in patients with chronic liver disease
Authors: Bauer A. G. C. , Wilson J. H. P. , Lamberts S. W. J. , Docter R. , Hennemann G. , Visser T. J.
Published: December 2008

Abstract. Possible arterio-venous gradients of T4, T3, rT3 and 3,3'-diiodothyronine (3,3'-T2) across the liver and the kidneys were measured in 9 patients with varying degrees of liver failure undergoing diagnostic catheterization. Plasma iodothyronine levels were measured in peripheral, hepatic and renal veins before and at 10-min intervals until 60 min after iv injection of 400 μg of TRH. In 2 patients estimated hepatic plasma flow and effective renal plasma flow were determined as well. In these 2 patients, no significant differences between iodothyronine levels in arterial and peripheral venous plasma were found. T4 and T3 levels were not significantly different between peripheral, renal and hepatic veins. Hepatic vein rT3 and 3,3'-T2 concentrations were 10.7 ± 8.3% (mean ± sd, P < 0.005) and 36 ± 18% (P < 0.001) lower than those in the peripheral vein (N = 9). Renal vein rT3 was just (6.2 ± 7.5%, P < 0.05) lower than rT3 in peripheral vein, whereas 3,3'-T2 was not different between the two veins. Estimates of hepatic and renal plasma flow were in agreement with values from the literature. On the basis of these data approximate hepatic clearance rates of 110 and 380 1/day for rT3 and 3,3'-T2 and a renal clearance rate of about 35 1/day for rT3 were calculated. Sixty min after TRH, plasma T3 was increased to 147 ± 56% (P < 0.05) and 3,3'-T2 in peripheral plasma was increased to 142 ± 36% (P < 0.025), whereas plasma T4 and rT3 did not change. These data suggest that the liver is the major site of plasma rT3 and 3,3'-T2 clearance in patients with mild liver disease and probably also in healthy humans. The kidneys may account for roughly 25% of plasma rT3 clearance. The increase in plasma 3,3'-T2 after TRH may be secondary to the rise in precursor T3, but thyroidal secretion of 3,3'-T2 is not excluded.
Effects of dexamethasone on ovarian activity in rats
Authors: de Greef W. J. , van der Schoot P.
Published: December 2008

Abstract. Rats with 5-day ovarian cycles were treated with dexamethasone (0.025 to 0.4 mg per rat per day) to examine its effects on ovarian activity. All doses of dexamethasone markedly suppressed endogenous secretion of ACTH as evidenced by decrease in weight of the adrenal glands after 7-23 days of treatment. Treatment with 0.4 mg of dexamethasone from the day of ovulation appeared to induce pseudopregnancy in more than 90% of the rats studied: pseudopregnancies lasted for 14-22 days. Induction of pseudopregnancy occurred less, in a dose-dependent fashion, when the lower doses of dexamethasone were administered. However, prolonged treatment with these lower doses resulted also in pseudopregnancy albeit after 1 or more cycles of 5 to 7 days. The effects of large doses of glucocorticoids on ovarian activity in rats, and possibly in humans as well, may be mediated predominantly through a stimulatory action of such drugs on prolactin secretion. Treatment with 0.4 mg per day of dexamethasone from the day before pro-oestrus did not interfere with ovulation and pseudopregnancy ensued this ovulation in all rats studied. Occasionally, unexpectedly large numbers of eggs per ovulating animal were found during treatment with dexamethasone. The data indicate failure of large doses of dexamethasone to interfere with ovulation and, possibly, induction of an increase in numbers of maturing follicles: this latter action deserves further analysis.
The addition of glipizide to insulin therapy in Type-II diabetic patients with secondary failure to sulfonylureas is useful only in the presence of a significant residual insulin secretion
Authors: Castillô Manuel , Scheen André J. , Paolisso Giuseppe , Lefébvre Pierre J.
Published: December 2008

Abstract. The present study aimed at 1) investigating the effect of a combined insulin + glipizide treatment on the metabolic control (HbA1c levels) and insulin requirements (Biostator® assessment) in ten non-obese Type-II diabetic patients with recent secondary failure to sulfonylureas; and 2) characterizing the relative contributions of changes in endogenous insulin secretion (C-peptide response) and insulin sensitivity (insulin-induced glucose disposal in clamped conditions) to this effect. The patients were treated in a randomized cross-over order with either insulin alone or insulin + glipizide (3 × 10 mg/day) during two periods averaging 6 weeks each. Mean HbA1c levels were similar in both experimental conditions (8.2 ± 0.6 vs 7.9 ± 0.6%, NS). In fact, during the combined therapy, HbA1c levels decreased in five subjects (from 8.6 ± 0.7 to 7.1 ± 0.5%; 'responders'), but not in the five others ('non-responders'); the 20-h Biostator insulin infusion was significantly decreased in the responders (29%; P < 0.05), but not in the non-responders. Basal (0.271 ± 0.086 vs 0.086 ± 0.017 nmol/l; P < 0.05) and post-glucagon (0.468 ± 0.121 vs 0.180 ± 0.060 nmol/l; P < 0.05) C-peptide plasma levels were significantly higher in the responders than in the non-responders; in addition, glipizide significantly increased basal C-peptide concentrations in the responders only (+ 68%; P < 0.05). The insulininduced glucose disposal was significantly increased by glipizide in the responders (+ 23%; P < 0.05), but not in the non-responders; however, this difference could be due to higher plasma free insulin levels (+ 37%; P < 0.02) during the clamp with glipizide in the responders who showed persistent C-peptide stimulation. Thus, combining glipizide with insulin seems to be useful only in Type-II diabetic patients who still have a significant endogenous insulin secretion capable of being stimulated by this compound.
Pharmacokinetics and urinary excretion of orally administered diiodotyrosine
Authors: Meinhold H. , Finke R. , Bogner U. , Schleusener H.
Published: December 2008

Abstract. Serum levels of diiodotyrosine (DIT) and urinary excretion rates of DIT and iodine were measured in 10 normal subjects after oral administration of 1.57 μmol of DIT corresponding to 400 μg of iodine. Serum DIT concentrations rose promptly from a mean endogenous basal level of 0.23 nmol/l to maximum values between 6.0 and 20 nmol/l within 30 min to 1 h after DIT ingestion. Decreasing DIT levels were found in all subjects 2 h after DIT intake. Urinary excretion of intact DIT was low, being less than 1% of the administered dose of exogenous DIT within 2 days. In contrast, 52% of the iodine administered in the form of DIT was excreted in the urine in the same time interval. The rapid absorption of DIT from the gastrointestinal tract combined with rapid and almost complete metabolic degradation by deiodination make orally applied DIT seem a suitable iodine carrier compound for therapeutic purposes.
Restoration of spermatogenesis by high levels of testosterone in hypophysectomized rats after long-term regression
Authors: Huang H. F. S. , Marshall G. R. , Rosenberg R. , Nieschlag E.
Published: December 2008

Abstract. In order to correlate the levels of intratesticular testosterone and the status of spermatogenesis, the present study examined the spermatogenic responses of mature chronically hypophysectomized (HPX) rats to different regimens of testosterone (T) replacement, i.e. implantation of a 2 × 5 or 6 × 5 cm long testosterone capsule (TC), or injection of 25 mg or 100 mg of testosterone enanthate (TE) every 4 days for 90 days. These regimens restored the testicular testosterone of the HPX rats to 25–96% of that measured in normal control rats. The testis weight of untreated HPX rats was below 30% of the normal control values. It was restored to 60–80% of control values in the TC implanted rats and to 50% in those receiving TE injection. Complete spermatogenesis of HPX rats was restored in those receiving TC implants and 100 mg TE injections. It was incomplete in those given 25 mg TE injections. Quantitative evaluation of germ cells revealed that spermatogonial populations of HPX rats were restored to 70 and 50% of the normal levels in rats receiving TC implants and TE injection, respectively. Differentiation of these cells resulted in the population of preleptotene spermatocytes to the same extent as those observed in spermatogonia. The yield of spermatids in both TC- and TE-treated HPX rats was below 50% of normal controls. Ratios between two successive generations of germ cells in stage VII epithelium revealed both dosage and regimen effects upon the yield of meiotic cells and spermatids. These results suggest that both T concentration and the mode of T availability to the testis may be important for specific steps of germ cell development in different stages of the cycle of the seminiferous epithelium. The results of the present study demonstrate that as little as 25% of normal testicular T concentration is sufficient to support all stages of spermatogenesis. Failure to restore a normal germ cell number even in the presence of a normal testicular T concentration suggests the need of other factors for quantitative spermatogenesis. Furthermore, despite a higher testicular T concentration achieved by TE injections, the restoration of spermatogenesis was less pronounced by this regimen. This finding suggests that the consistency of testicular T may also be important for normal spermatogenesis.
The polymorphic pattern of somatomedins during human development
Authors: Blum Werner F. , Ranke Michael B. , Lechner Brigitte , Bierich Jürgen R.
Published: December 2008

Abstract. Human somatomedins (Sm) are heterogeneous on separation by chromatofocussing. Besides the 'classic' insulin-like growth factor I and II (IGF-I/Sm-C and IGF-II), a number of minor peaks emerge which can be classified as IGF-I/Sm-C-like or as IGF-II-like. The aim of the current study was to investigate whether or not polymorphism of somatomedins is present in individuals and whether or not the polymorphic pattern changes during development. Serum extracts from normal healthy children and adults were fractionated by chromatofocussing and the various somatomedin-like peptides were quantitated by specific radioimmunoassays for IGF-I/Sm-C or IGF-II. The results demonstrate 1) that heterogeneity of somatomedins is a common phenomenon existing in all individuals studied, and 2) that the polymorphic patterns of the IGF-I/Sm-C-family and of the IGF-II-family remain rather stable during development, although minor changes are evident.
Some qualitative differences of hCG in serum from early and late pregnancies and trophoblastic diseases
Authors: Wide Leif , Hobson Bruce
Published: December 2008

Abstract. Twenty-four sera were obtained from women in the first and third trimester of pregnancy, women with gestational choriocarcinoma, and men with testicular hCG-producing tumours. The hCG-activity was measured by an in vivo bioassay (B) based upon the increase in mouse uterine weight. The sera were also analysed by three immunoassays (I), one for hCG, one for α-hCG subunits, and one for β-subunits. All sera were also subjected to electrophoresis in 0.17% agarose suspension in 0.075 mol/l sodium veronal buffer at pH 8.6, and median charge, expressed as median mobility, was estimated for hCG. The metabolic clearance rate (MCR) of hCG in serum in early and late pregnancy and from one patient with choriocarcinoma was measured in mice. The B/I ratio was lower and the forms of hCG were less negatively charged in late pregnancy compared with early pregnancy. The lower B/I ratio might be due to the higher MCR of hCG in the test animal in the in vivo bioassay. The B/I ratio in choriocarcinoma was higher than in early pregnancy. However, the median charge of hCG was almost identical in these two groups. The most negatively charged forms of hCG were found in the men with testicular tumours. The four groups: early pregnancy, late pregnancy, gestational choriocarcinoma, and testicular tumours could be differentiated by measuring the median charge and the B/I ratio of hCG in serum. The production, later in pregnancy, of forms of hCG which disappear faster from the circulation might partially explain the lower hCG concentration in serum at this stage of gestation.
Hair growth and androgen responses in hirsute women treated with continuous cyproterone acetate and cyclical ethinyl oestradiol
Authors: Jones D. B. , Ibraham I. , Edwards C. R. W.
Published: December 2008

Abstract. Eighteen hirsute women (8 with polycystic ovarian syndrome, 10 with idiopathic hirsutism) were treated for up to 12 months with cyproterone acetate, 150 mg daily, and ethinyl oestradiol, 50 μg on days 5–25 of the menstrual cycle. Hair growth rate and density were measured from standardized serial photographs of a shaved skin area. A significant reduction was seen in mean hair growth rate, total plasma testosterone, free testosterone index, plasma dehydroepiandrosterone, and plasma androstenedione. LH and FSH also fell and sex hormone binding globulin level increased. No significant changes occurred in hair density or in serum PRL levels. A significant correlation was observed between hair growth rate and total plasma testosterone for the pooled results (r = 0.35, P < 0.005). No significant correlations were seen between hair density and the endocrine parameters studied.
Detection of heterozygous carriers for 21-hydroxylase deficiency by plasma 21-deoxycortisol measurement
Authors: Gourmelen M. , Gueux B. , Trung M. T. Pham Huu , Fiet J. , Raux-Demay M. C. , Girard F.
Published: December 2008

Abstract. Using a highly specific radioimmunoassay recently described, plasma 21-deoxycortisol levels were measured in 55 heterozygous carriers of 21-hydroxylase deficiency (as demonstrated by HLA typing). Mean baseline 21-deoxycortisol levels were above the normal range, but there was a 38% overlap with control values. In contrast to 17-hydroxyprogesterone levels, which in 71% of the subjects remained within the normal range one hour after ACTH stimulation, 21-deoxycortisol levels increased over stimulated control levels in all but two heterozygous carriers. No differences as to the levels were observed between heterozygous carriers for the classic and the late-onset forms. Plasma 21-deoxycortisol measurement appears to be a valid tool in the biological detection of heterozygosity for 21-hydroxylase deficiency and its implications in genetic counselling.
Effects of aldosterone on intralymphocytic sodium and potassium in patients with primary aldosteronism
Authors: Wehling Martin , Kuhls Stefan , Witzgall Helmut , Kuhnle Ursula , Armanini Decio , Theisen Karl
Published: December 2008

Abstract. In vitro effects of aldosterone have been described with regard to the intracellular sodium and potassium concentrations of human mononuclear leukocytes. In the present paper the in vitro effect of aldosterone on the intracellular sodium and potassium of human mononuclear leukocytes in 6 patients with primary aldosteronism was investigated. Except for one patient with elevated intracellular electrolytes, sodium and potassium in mononuclear leukocytes of patients with aldosteronism without incubation were within the range for normals. In the patients, no significant change of intracellular sodium or potassium was observed during incubation with or without aldosterone (1.4 nmol/l), whereas in normals, the loss of sodium and potassium during incubation without aldosterone was prevented by 1.4 nmol/l aldosterone. This insensitivity to aldosterone indicates that intracellular electrolytes in mononuclear leukocytes of patients with primary aldosteronism are kept in normal ranges by mechanism which are independent of mineralocorticoids and may represent the cellular correlate to the renal 'escape' phenomenon in aldosteronism.
Exit of inhibin-like bioactivity from gonadotropin-stimulated prepubertal pig ovaries
Authors: Sairam M. R. , Downey B. R.
Published: December 2008

Abstract. Inhibin-like bioactivity (IBA) was assessed by bioassay in the follicular fluid, ovarian venous plasma, and peripheral plasma of immature gilts in which follicular development had been synchronized by administration of pregnant mare serum gonadotropin (PMSG) and hCG. IBA was detectable in the pooled follicular fluid of control animals, but the concentration as well as the total content increased markedly with the growth of the follicle induced by PMSG. About 36–72 h after PMSG treatment, IBA was found consistently in the venous plasma of both ovaries, although in controls as well as after ovulation (i.e. +48 h after hCG) IBA was not detected. The amount of IBA exiting the ovary by way of venous circulation was only a small fraction (< 1%) of the total activity calculated to be in each ovary at a given time. IBA was undetectable in the peripheral plasma at any sampling time. On the basis of these results we could speculate that other routes of entry of inhibin into peripheral circulation may exist in the immature pig and/or that the predominant action of IBA might be within the follicle itself.
Isoelectric properties, lectin binding characteristics and biological activities of neuraminidase-treated rat LH components
Authors: Hattori Masa-aki , Ozawa Kazunori , Wakabayashi Katsumi
Published: December 2008

Abstract. The present study was performed to evaluate the different carbohydrate structure of rat LH isoelectric components related to their intrinsic biological activities. Terminal sialic acid residues were essential to the formation of multiple LH components observed in the isoelectric focussing profile, which was proved by their interaction with Ricinus communis agglutinin-120 following neuraminidase treatment, and the conversion of component F (pI, 10.0) to less alkaline components after incubation with liver Golgi membrane fraction in the presence of CMP-NeuNAc. The affinity studies using lentil lectin indicated that component F was not an asialo form of component A (pI 8.4). The serial removal of sialic acid residues from these components led to increases in the steroidogenic activity, owing to increases in the activation of the receptor-adenylate cyclase system. The enhancement of the steroidogenic activity by desialylation was very great in component A'(pI, 8.0) (751% increase), and decreased with increasing pI. It can be concluded that the different biological potencies of intact LH components are attributable principally to terminal sialic acid residues. However, the peripheral chains of asialo oligosaccharides of less alkaline components (pI, 8.0, 8.4) seem to prevent the maximal cellular responses, since their desialylated forms did not attain the maximum activity.
Effects of corticotropin-releasing hormone on insulin and glucagon secretion in mice
Authors: Karlsson Sven , Ahrén Bo
Published: December 2008

Abstract. Besides in the brain, corticotropin-releasing hormone occurs in the pancreas. Therefore, its effects on plasma levels of insulin and glucagon were investigated in vivo in the mouse. At 2 min after CRH injection (0.5–8.0 nmol/kg), plasma insulin was lowered: by 4.0 nmol/kg from 38 ± 4 to 28 ± 2 mU/l (P < 0.05). Plasma insulin was lowered also at 6 min, whereas at 10 min, plasma insulin levels were elevated (P < 0.05). Plasma glucagon levels were slightly lowered (P < 0.05) at 10 min after CRH injection, whereas plasma glucose was slightly elevated (P < 0.05) at 6 min after injection but not at 2 or 10 min. The effects of CRH on the plasma insulin and glucagon response to iv injections of half-maximal dose levels of glucose (2.8 mmol/kg) or the cholinergic agonist carbachol (0.16 μmol/kg) were also investigated. CRH, 4.0 nmol/kg, however, could not influence the plasma insulin or glucagon levels after the iv injection of either glucose or carbachol. Thus, CRH slightly affects basal plasma levels of insulin and glucagon in mice. In contrast, stimulated insulin and glucagon secretions are not affected by CRH. Peripheral CRH may therefore be of slight importance for the regulation of basal plasma levels of insulin and glucagon in the mouse.
Insulin/C-peptide response to intravenous glucagon
Authors: Snorgaard Ole , Hasselstrøm Kjeld , Lumholtz lb Bo , Thorsteinsson Birger , Siersbæk-Nielsen Kaj
Published: December 2008

Abstract. The C-peptide and insulin secretory responses to increasing doses of iv glucagon (1, 2, 5, 10 μg/kg body weight and I mg (only diabetics)) were investigated in six lean non-insulin-dependent diabetic patients and six normal subjects, matched for body weight and fasting blood glucose concentrations. A well defined relationship between glucagon dose and the C-peptide/insulin response was observed in both groups. The course of the dose-response curves was significantly different in diabetics. The maximal obtainable C-peptide response (E-max) was reduced to 53% of the response in normal subjects (P = 0.037), and the insulin response was reduced to 52% (P = 0.014). E-max was reached in diabetics with only 10 μg/kg of glucagon, whereas higher doses seem to be needed in the control group. However, the glucagon dose causing 50% of E-max (ed50) was not significantly higher. Thus, the widely accepted use of 1 mg of glucagon to test residual beta cell function secures a maximal response of both insulin and C-peptide in non-insulin-dependent diabetic subjects. In addition, our data support the theory that beta cell deficiency is a basic feature of non-insulin-dependent diabetes.
Existence of nuclear thyroid hormone receptors in the porcine thyroid gland and the rat thyroid cell line FRTL-5
Authors: Nakamura Hirotoshi , Imura Hiroo
Published: December 2008

Abstract. We have investigated whether nuclear T3 receptors exist in the thyroid cell. Nuclear proteins extracted from porcine thyroid nuclei with 0.4 mol/l KCl were incubated with [125I]T3. The mixture was then analysed by sucrose density gradient ultracentrifugation which revealed that the T3-binding proteins migrated at the same position of 3.6 S as rat liver nuclear T3 receptors. Fractionation by high performance liquid chromatography using a size exclusion column and an ion exchanger column also demonstrated elution patterns of T3-binding similar to those of the rat liver receptor. Scatchard plots of crude nuclear extracts from porcine thyroid represented a curvilinear pattern. However, when the nuclear proteins partially purified by a DEAE column chromatography were analysed, a single binding component was found; the association constant was 4.1 × 1010 l/mol and the maximal binding capacity was 602 fmolT3/mg protein. Displacement study with several T3 analogues showed a highly selective affinity for L-T3. Cultured rat thyroid cells of the FRTL-5 line also contained a single class of saturable, high affinity T3-binding site. Subconfluent cells in 100-mm dishes were incubated with increasing amounts of [125I]T3 at 37°C for 3 h and radioactive T3 in isolated nuclei was counted. Scatchard analysis of data showed that the association constant and the maximal binding capacity were 3.44 ± 0.63 × 1010 1/mol and 63.7 ± 17.8 fmolT3/mg protein, respectively. These results strongly suggest that there are nuclear T3 receptors, indistinguishable from the hepatic T3 receptors, in the porcine thyroid and rat FRTL-5 cells.
Thyroid autonomy: sensitive detection in vivo and estimation of its functional relevance using quantified high-resolution scintigraphy
Authors: Bähre Manfred , Hilgers Reinhard , Lindemann Corinna , Emrich Dieter
Published: December 2008

Abstract. This study is concerned with 236 euthyroid individuals living in an area of iodine deficiency, 227 of whom had endemic goitres. In these subjects, autonomy could be suspected owing to an inhomogeneous activity distribution on the thyroid scintigram or a subnormal TSH response to TRH. They complete a total number of 426 investigated individuals. Previously, in 190 separated controls without evidence of autonomy, the reference ranges for the thyroid 99mTc pertechnetate uptake under suppression (TcUs), a measure for the non-suppressible thyroid iodide clearance, and for suppressibility of circumscribed thyroid regions, had been determined. These two parameters obtained by highresolution quantified scintigraphy were used for an accurate detection of thyroid autonomy among the 236 individuals. Suppression scintigraphy revealed autonomy in 171 patients. ΔTSH after TRH was subnormal in 40% of the subjects with abnormal thyroid suppressibility. Prevalence of abnormal suppression was dependent on three factors: patient age, goitre type and estimated thyroid weight. In the total investigated collective, the prevalence of autonomy was 77% in patients with a goitre weight above 50 g. The individuals with abnormal suppression were grouped into four classes of TcUs. In these classes, free thyroxine index (FT4I) and total triiodothyronine (TT3) increased with increasing TcUs, whereas ΔTSH decreased. This finding indicates a continuum of different extents of autonomous thyroid function, whereas in the individual patient, the extent can be determined using the pertechnetate uptake under suppression. In addition, FT4I, TT3 and ΔTSH in each of the TcUs classes depended on the individual iodine supply. It is concluded that, in patients with thyroid autonomy, actual thyroid hormone concentrations and TSH stimulation are determined by two major factors: the extent of autonomy and the individual iodine supply. Therefore, in iodine deficiency, the TRH test may be normal, although autonomy is present. This relationship explains the reduced sensitivity of the TRH test to detect autonomy in iodine-deficient goitres.
Evaluation of TSH-receptor antibodies as prognostic markers after cessation of antithyroid drug treatment in patients with Graves' disease
Authors: Kasagi Kanji , Iida Yasuhiro , Hatabu Hiroto , Tokuda Yasutaka , Arai Keisuke , Endo Keigo , Konishi Junji
Published: December 2008

Abstract. Clinical usefulness of thyroid-stimulating antibodies (TSab) and TSH-binding inhibitor immunoglobulins (TBII) for predicting the prognosis in patients with Graves' disease after cessation of antithyroid drug treatment was evaluated, and compared with that of T3 suppression test and goitre size. Among 46 patients who had been euthyroid on a maintenance dose of antithyroid drugs for at least one year and had discontinued taking medicine, 16 relapsed within one year (group 1), 7 relapsed later than 1 year (group 2), and 23 patients remained in remission for more than 1 year (group 3). Incidence of TSab, TBII, T3 nonsuppressibility and large goitre (transverse diameter longer than means of the values for the 46 patients: ≥ 4.36 cm in females; ≥ 4.74 cm in males) determined at the time of discontinuation of treatment was 87.5% (14/16), 56.3% (9/16), 78.6% (11/14) and 81.3% (13/16) in group 1; 66.7% (4/6), 28.6% (2/7), 50.0% (3/6), and 57.1% (4/7) in group 2, and 56.5% (13/23), 24.1% (5/23), 35.7% (8/23), and 26.1% (6/23) in group 3, respectively. All relapsed patients showed remarkable increases in both TSab and TBII activities at the time of relapse. High incidence of TSab in patients remaining in remission suggests that a reduced functional reserve of the thyroid, probably owing to destructive changes and/or shrinkage of the gland, may cause impaired responses to TSab and is involved in the cause of remission. Development of blocking type of TBII was not considered to be a cause of remission. Remission was predictable in all patients with any two of the indices such as negative TSab, positive T3 suppressibility, and small goitre.
Relaxin: a mammotropic hormone promoting growth and differentiation of the pigeon crop sac mucosa
Authors: Bigazzi Mario , Bani Gastone , Sacchi Tatiana Bani , Petrucci Fabrizia , Bianchi Stefano
Published: December 2008

Abstract. The pigeon crop sac is responsive to local administration of mammotropic hormones independently of systemic hormonal influences. We showed previously in mice that relaxin promotes growth of the mammary gland only after pre-treatment with estrogen. In this study we investigated whether relaxin, locally administered, has a stimulatory effect without estrogen pre-treatment. The results of this study show that relaxin stimulates the crop sac mucosa causing changes in its gross appearance and histological modifications indicating enhanced growth and differentiation of the mucosal epithelium. The effects of relaxin are dose-related, as demonstrated by the increases of the wet and dry weights, the [3H]thymidine and [3H]uridine uptakes of the mucosa, and the histochemically detectable DNA content of the mucosal epithelium. These results strengthen the idea that relaxin should be included in the list of mammotropic hormones.
Phagocytotic activities of latex beads by FRTL cell: possible interaction of cell surface glycoprotein
Authors: Takazawa Kazunaga , Endo Toyoshi , Onaya Toshimasa
Published: December 2008

Abstract. We investigated the phagocytotic activity of cultured rat thyroid cells (FRTL) by using latex beads. FRTL cells ingested many carboxylate-modified polystyrene latex beads (c-latex beads), which had carboxyl residues on the surface, whereas they ingested few polystyrene latex beads (p-latex beads), which had no electrostatic charge. Phagocytotic activity of c-latex beads was stimulated by TSH in a dose-related manner. Dibutyryl, 8-bromo-cAMP, and forskolin also stimulated this process. Tunicamycin significantly inhibited dibutyryl cAMP-stimulated phagocytotic activity of clatex beads by FRTL cells. N-acetylglucosaminidase also inhibited dibutyryl cAMP-stimulated phagocytosis. These results suggest that the interaction between negative surface charge of c-latex beads and positive surface charge probably induced by N-acetylglucosamine in the cell surface glycoprotein, might play an important role in the phagocytosis of FRTL cells.
Effects of somatostatin and serotonin on calcitonin secretion from cultured rat parafollicular cells
Authors: Endo Toyoshi , Saito Tsukasa , Uchida Takashi , Onaya Toshimasa
Published: December 2008

Abstract. A primary culture of mammalian parafollicular cells was established from rat thyroid glands in order to investigate the effects of serotonin and somatostatin on calcitonin secretion. Minced rat thyroid glands were dissociated with collagenase and cultured in a Ham's F-12K medium supplemented with calf serum (5%), insulin (1.3 × 10−6 mol/l), hydrocortisone (10−8 mol/l), transferrin (6.1 × 10−9 mol/l), and glycyl-L-histidyl-L-lysin (2.5 × 10−8 mol/l). Immunohistochemical peroxidase-antiperoxidase method revealed that the cultured parafollicular cells were immunopositive for human calcitonin, and electron microscopy demonstrated the existence of dense secretory granules in the cultured parafollicular cells. Addition of the Ca2+ to the culture medium stimulated calcitonin secretion from the cells dose-dependently as measured by radioimmunoassay. Pre-incubation of serotonin with the cells produced higher calcitonin levels in a dose-dependent manner. On the other hand, pre-incubation of somatostatin with the cells significantly inhibited calcitonin secretion.
Suppressed plasma prolactin response to thyrotropin-releasing hormone in hyperthyroidism reproduced by thyroxine but not by triiodothyronine administration to normal subjects
Authors: Erfurth Eva Marie , Hedner Pavo
Published: December 2008

Abstract. In 10 hyperthyroid women studied in the follicular phase of the menstrual cycle, basal plasma PRL was normal, but PRL release after TRH was significantly suppressed compared with that in 11 control women. The suppressed PRL response to TRH was not explained by changes in serum estradiol or sex hormone-binding globulin. It recovered after treatment of hyperthyroidism. When normal women were treated with T4 (0.5 mg daily for 6 to 10 days), their mean serum free T4 level increased to about 70% of that in the hyperthyroid patients, whereas their serum free T3 levels increased to a lesser degree. During T4 administration, these women had PRL changes similar to those of the hyperthyroid patients. When the normal women took T3 (60–120) μg for 6 to 8 days), their serum free T3 increased to almost the level of the hyperthyroid patients, but the TRH stimulated PRL release remained close to the control level. The PRL increase after dopaminergic blockade with metoclopramide was significantly suppressed in hyperthyroid patients, and they had no PRL response to TRH after pretreatment with metoclopramide. In conclusion, the PRL changes in hyperthyroidism were reproduced by administration of T4, but not by administration of T3 to healthy women. The site of action is suggested to be pituitary, but additional hypothalamic effects cannot be excluded.
In vitro cellular interactions among thyrocytes, T cells and monocytes from patients with Graves' disease
Authors: Otsubo Toshio , Eguchi Katsumi , Shimomura Chikako , Ueki Yukitaka , Tezuka Hiroshi , Ishikawa Naofumi , Ito Kunihiki , Nagataki Shigenobu
Published: December 2008

Abstract. In order to investigate the cellular interactions among thyrocytes, T cells and monocytes in thyroid glands from patients with Graves' disease, we determined alterations of HLA-DR antigen expression on thyrocytes and T cells, and the production of interferon-γ during coculture of thyrocytes, T cells and monocytes obtained from patients with Graves' disease. Thyroid glands were obtained at operation from 17 patients with Graves' disease. When thyrocytes and autologous peripheral blood T cells were cocultured for 7 days, the percentage of HLA-DR antigen expression on thyroyctes was significantly increased by T cells and that on T cells was also significantly increased by thyrocytes. Addition of autologous monocytes to the mixtures of thyrocytes and T cells significantly increased the expression of HLA-DR antigens on both thyrocytes and T cells compared with mixtures without monocytes. In culture supernatants, inteferon-γ was detected in 4 of 14 cocultures of thyrocytes and T cells, in 5 of 10 cocultures of thyrocytes, T cells and monocytes, but not in any cultures of thyrocytes alone, T cells alone and T cells and monocytes. Induction of HLA-DR antigen expression on thyrocytes and T cells was blocked by addition of anti-interferon-γ monoclonal antibody to the mixture. These results suggest that HLA-DR antigen positive thyrocytes are able to induce the HLA-DR antigen expression of T cells in the presence of monocytes, and the activated T cells are capable of producing interferon-γ which acts on thyrocytes to induce and maintain the expression of HLA-DR antigens.
The effect of pirenzepine on growth hormone and blood glucose levels in Type I diabetes mellitus
Authors: Pietschmann P. , Schernthaner G.
Published: December 2008

Abstract. Increased GH levels in Type I diabetes mellitus have been implicated in the pathogenesis of metabolic complications such as the so-called dawn phenomenon. GH secretion is under control of cholinergic mechanisms. In 21 Type I diabetic patients the effect of oral administration of the anticholinergic drug pirenzepine in addition to intensive insulin therapy on GH and blood glucose levels was studied. At 21.30, 08.00 and 12.00 h, all patients received in random order 50 mg of pirenzepine or placebo po. Blood for determination of GH, blood glucose, cortisol and Cpeptide levels were obtained at 3-h intervals. Serum levels of plasma glucose and GH were significantly lower under pirenzepine than under placebo (P < 0.05 and P < 0.01, respectively). Serum levels of cortisol, free insulin and C-peptide were comparable on the test and the control day. Our data indicate that in Type I diabetes mellitus the anticholinergic drug pirenzepine is effective in decreasing both GH and blood glucose levels.
Effect of voluntary intake of iodinated salt on prevalence of goitre in children
Authors: Hintze Gerhard , Emrich Dieter , Richter Klaus , Thal Hanne , Thal Horst , Wasielewski Thomas , Köbberling Johannes
Published: December 2008

Abstract. The availability of iodinated salt containing 20 mg of iodine as iodate/kg salt consumed on a voluntary basis enabled us to investigate its effect on goitre prevalence and iodine excretion in urine in a longitudinal, prospective, randomized study over 4 years. With this salt, under the assumption of a consumption of 5 g salt per day and person, an additional intake of 100 μg of iodine can be achieved. The study was performed on initially 334 children (168 boys, 166 girls) at the age of 10 years living in an area of iodine deficiency. After 4 years, 286 children still participated in the study. Initially, goitre prevalence as assessed by palpation was found to be 30.5% (37.4% in girls and 23.8% in boys). Neck circumference was found to be significantly higher in children with goitre compared with those without (30.2 ± 1.4 vs 29.4 ± 1.4 cm; P < 0.001). Iodine excretion in the urine was significantly lower in children with goitre compared with those without (40.4 ± 16.7 μg/g creatinine vs 46.1 ± 24.9 μg/g creatinine; x ± sd; P < 0.05). The children were randomly assigned to two different groups: group A (N = 146) was asked to use iodinated salt, group B (N = 188) non-iodinated salt. Over the 4 years, a continuous increase in iodine excretion in urine could be demonstrated in group A. After 1 year, it was significantly higher than in the control group that used non-iodinated salt. After 4 years, the mean iodine excretion in children using iodinated salt was 60.1 ± 24.1 μg/g creatinine in contrast to 45.1 ± 18.6 μg/g in the control group (x ± sd; P< 0.0001). However, no decrease in goitre prevalence could be documented: after 4 years, 23.8% of the children belonging to the group using iodinated salt and 22.5% of those in the group taking non-iodinated salt had a goitre. From these observations we conclude: 1. The voluntary use of a commercially available iodinated salt containing 20 mg iodate/kg leads to a significant increase in iodine intake, measured by urinary iodine excretion. Even after 4 years, the value is far below the daily iodine intake recommended by the WHO. No decrease in goitre frequency could be assessed. 2. An increase in iodine ingestion can be achieved either by increasing the iodine content of the salt or by application of iodine by alternative measures. The safest way would be to use iodinated salt exclusively, i.e. also in the food industry and restaurants. An increase in the iodine content of the salt and its continuous voluntary use would lead to a large variation in iodine intake. A higher risk of adverse reaction, e.g. iodine-induced thyrotoxicosis, cannot be excluded in susceptible persons.