bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE PHARMACOKINETICS, SAFETY AND ENDOCRINE EFFECTS OF AUTHENTIC BIOSYNTHETIC HUMAN GROWTH HORMONE IN NORMAL SUBJECTS
Authors: HO K. Y. , WEISSBERGER A. J. , STUART M. C. , DAY R. O. , LAZARUS L. 
Published: March 2008

SUMMARYThe pharmacokinetics, safety and endocrine effects of an authentic human growth hormone (bio‐hGH), produced by the expression of genomic hGH in a mammalian cell line, were studied in six healthy young men who were administered 0.2 U/kg/day subcutaneously for five consecutive days. Changes in sodium balance and in thyroid function were studied during the week of bio‐hGH administration and safety parameters were monitored over a 3‐week period. Growth hormone levels reached a mean (±SD) peak of 106 ± 10 mIU/1 at 3.3 ± 0.5 h following the first dose and resulted in a significant rise of somatomedin C, free fatty acids, fasting blood glucose and insulin concentrations. Bio‐hGH administration resulted in a significant increase in body weight (80.0± 4.5 to 81.1 ± 4.3 kg; P<0.01) which was associated with a marked reduction in urinary sodium excretion (196 ± 38 to 45 ± 20 mmol/day; P<0.025). Serum T3 increased during bio‐hGH administration and was asssociated with reciprocal changes in free thyroxine and TSH concentrations. Cardiac, hepatic, renal, biochemical, haematological, endocrinological and immunological functions remained normal throughout the study. No antibodies to hGH or to host cell protein developed during the study. The results show that bio‐hGH is safe in the short term, well tolerated, possesses pharmacokinetic and biological properties similar to pituitary hGH, and has distinct effects on sodium balance and on thyroid function. This study stresses the need to monitor patients for effects on sodium retention, carbohydrate metabolism and thyroid function when using hGH doses of 1.0 U/kg/week (40U/m2/week) or more in patients with GH responsive short stature.
INCREASED GH RESPONSE TO GHRH IN NORMAL TALL MEN
Authors: BATRINOS M. , GEORGIADIS E. , PANITSA‐FAFLIA CH. , STRATIGOPOULOS S. 
Published: March 2008

SUMMARYThe importance of growth hormone secretion to the growth of an individual raises the question of the role that the secretory capacity of this hormone may play in defining the variations of height within the population. To investigate this problem we studied the response of GH to GHRH in 20 normal tall (mean ± SD height 190.8 ± 2.4 cm, range 187–196 cm) adult males of the third decade and in 17 age‐matched controls of average height (mean ± SD height 173.8 ± 1.6 cm, range 171.177 cm). Synthetic GHRH (1.29) NH2 (Kabi, Vitrum, Sweden) was administered at 0800 h after an overnight fast and blood was drawn for GH assay. In the tall subjects basal GH concentrations at – 15 and 0 min were not significantly different from those of the controls. However, the tendency to higher basal GH levels and spontaneous peaks was evident in tall individuals. Only three basal GH values were below 1 pg/1 (0.8–0.9 μg/1; μg/l = 2mU/l) in the tall individuals while 24 of 33 basal GH values in the controls ranged between 0.25 and 0.87 μg/l. At +15 and +30 min after GHRH the rise in GH was significantly greater in the tall subjects. Moreover, the integrated area under the response curves was significantly greater in the tall subjects than the controls (P<0.01). No differences in the mean serum testosterone and prolactin levels were found in the two groups.It is postulated that if this enhanced pituitary responsiveness is constant and chronic in tall individuals a definite relation of their stature to the GH secretion is to be anticipated.
CORTICOSTEROID‐BINDING GLOBULIN IN DEPRESSION
Authors: LEAKE A. , GRIFFITHS H. W. , PASCUAL J. A. , FERRIER I. N. 
Published: March 2008

SUMMARYWe undertook this study to evaluate the role of plasma free and total Cortisol, and corticosteroid‐binding globulin (CBG) in depression. Plasma was collected from 15 drug‐free depressed patients and 15 age and sex‐matched control subjects at 0900 and 2300 and at 1600 following an oral dose of dexamethasone. Depressed patients had elevated concentrations of both free and total Cortisol at all time points studied. The binding capacity and affinity of plasma CBG for Cortisol was similar in both groups at all times studied. No differences in CBG measures were noted if the depressed subjects were divided into elderly or younger subjects and dexamethasone suppression test (DST) suppressors or non‐suppressors.
LEUCOCYTE SODIUM CONTENT AND SODIUM PUMP ACTIVITY IN OVERWEIGHT AND LEAN HYPERTENSIVES
Authors: NG L. L. , HARKER M. , ABEL E. D. 
Published: March 2008

SUMMARYLeucocyte sodium content and sodium pump activity was studied in overweight and lean hypertensive subjects and normotensive controls, all in the fasting state. In lean subjects (body mass index < 27 kg m−2), hypertensives did not have altered leucocyte sodium content or pump activity. In the overweight (mostly obese) subjects, the leucocyte sodium content was higher in hypertensive than in normotensive subjects (median (range) 56.1 (42.0–84.1) vs 320 (18.2–59.4) mmol kg−1, P< 0.001). This raised sodium content in overweight hypertensives was associated with a lower (ouabain‐sensitive) 22Na efflux rate constant (2.25 (1.15–3.01) vs 2.64 (1.98–3.61) h −1, P < 0.05) and a higher passive (or ouabain‐insensitive) 22Na efflux rate constant (0.90 (0.53–1.18) vs 0.63 (0.21–1.09) h−1, (P < 0.01). The systolic and diastolic blood pressures were significantly correlated to intracellular Na+ in the overweight group (r=0.41 and 0.56, P< 0.02 and 0.001 respectively). Thus, hypertension in the overweight subjects is associated with accumulation of intracellular sodium that may be due to abnormalities of the active sodium pump, though changes in ouabain‐insensitive mechanisms also occur.
GONADOTROPHIN‐RELEASING HORMONE AND HUMAN CHORIONIC GONADOTROPHIN TESTS REVEAL THAT BOTH HYPOTHALAMIC AND TESTICULAR ENDOCRINE FUNCTIONS ARE SUPPRESSED DURING ACUTE PROLONGED PHYSICAL EXERCISE
Authors: KUJALA URHO M. , ALEN MARKKU , HUHTANIEMI ILPO T. 
Published: March 2008

SUMMARYThe mechanism of suppression of gonadotrophins and; testosterone during prolonged exercise was studied. Fourteen healthy males were injected immediately before an exhaustive bicycle run for 4 h, and; before a control period without exercise, with one of the following substances: (1) 1 ml of saline, (2) 100 μg of a GnRH agonist (buserelin), and; (3) 50 IU/kg of hCG. Each test was repeated for each subject 2 weeks apart, in a randomized single‐blind fashion. Blood samples were taken before the injections (sample A), 6 h after the injections (sample B), and; the following morning (sample C). During placebo treatment testosterone concentration decreased from A samples to B samples more in the exercise trial than in rest trial (31 vs 8%, P =0.02). This exercise‐associated decrease was reversed by both the GnRH agonist and; hCG treatments. Serum gonadotrophin concentrations responded identically to GnRH agonist injections during exercise and rest trials. hCG resulted in a greater increase of serum testosterone from A to C samples at rest than during the exercise trial (52 vs 33%, P=0.04). In conclusion, the exercise‐induced suppression of serum testosterone is associated with two effects: suppressed endogenous GnRH stimulation of gonadotrophin release during exercise, and decreased testicular capacity to secrete testosterone during recovery period.
SUBCUTANEOUS GROWTH HORMONE‐RELEASING HORMONE AUGMENTS PULSATILE NOCTURNAL GH RELEASE IN GH‐INSUFFICIENT CHILDREN, BUT MAY ALSO RAISE BASAL GH SECRETION
Authors: ROSS R. J. M. , KIRK J. M. W. , TSAGARAKIS S. , TRAINER P. J. , CICCARELLI E. , TOUZEL R. , GROSSMAN A. , SAVAGE M. O. , BESSER G. M. 
Published: March 2008

SUMMARYGrowth hormone‐releasing hormone (GHRH) when given s. c. to GH‐insufficient children either as pulses, or once or twice daily, promotes linear growth. These treatment regimens, however, are not ideal as they require frequent drug administration and a significant proportion of patients do not show improved growth. We have now investigated the GH response to a nocturnal s. c. infusion of GHRH(1–29)NH2, at two dosages, 5 and 10 μg/kg/h, in a group of five GH‐insufficient children. The s. c. infusion of GHRH between 2100 h and 0600 h augmented nocturnal pulsatile GH release in all five children. There was a dose‐dependent response for the GH area under the curve (AUC), and mean total GH concentration. The AUC for GH was significantly greater after the 10 than 5 μg/kg/h GHRH which in turn was greater than that after placebo; mean (SD) AUC: 14816 (3978), 8125 (1931), 3032 (1582) mU min/1 respectively (P < 0.01 and P < 0.05). There was no significant change in the number of GH pulses during the 9‐h infusions when the subjects were infused with GHRH 10 or 5 pg/kg/h compared to placebo, and they occurred at similar times although the number of pulses tended to be greater after GHRH; the mean (SD) numbers of GH pulses were 5.0 (0‐7), 3.8 (0.8), 3.2 (0.8), respectively. There was however a significant rise in the mean baseline GH concentration in all patients during the infusion of GHRH 10 or 5 μg/kg/h compared to placebo, but not with 5 μg/kg/h. Thus, GHRH(1–29)NH2 given s. c. augmented nocturnal pulsatile GH release in GH‐insufficient children but it also increased baseline GH secretion. These results suggest that a sustained release preparation of GHRH could be a potential treatment for GH‐insufficient children, and that a dose of 5 μg/kg/h would promote pulsatile GH release, but that at higher dosage it may also raise basal GH secretion.
THE INTERACTION BETWEEN CLONIDINE AND GROWTH HORMONE RELEASING HORMONE IN THE STIMULATION OF GROWTH HORMONE SECRETION IN MAN
Authors: SURI D. , HINDMARSH P. C. , BRAIN C. E. , PRINGLE P. J. , BROOK C. G. D. 
Published: March 2008

SUMMARYSix normal adult males were given clonidine and GHRH either separately, or in combination, in random order. The peak serum GH concentrations elicited by clonidine or GHRH were variable but one factor influencing the GH response to GHRH was the GH secretory status in the hour prior to the administration of the GHRH. Peak serum GH concentrations attained were significantly greater when serum GH concentrations were rising (mean 52.9 mU/l, SD 17.2) than if they were falling (mean 27.5 mU/l, SD 13.3) or unchanged/undetectable (mean 20.6 mU/l, SD 9.8) (one‐way ANOVA, F=8.77; P= 0.004). The GH response to clonidine was not influenced by the secretory status in the hour prior to administration of clonidine. Pretreatment with clonidine did not augment the peak serum GH response to GHRH but the direction of response was more predictable than when GHRH was administered separately or repeatedly. Prior treatment with GHRH(1–29)‐NH2 led to a marked attenuation of the peak serum GH response to clonidine. These results suggest that the alpha‐2 adrenergic agonists probably stimulate GH secretion through pathways other than just GHRH.
HORMONAL STUDIES ON WOMEN WITH POLYCYSTIC OVARIES DIAGNOSED BY ULTRASOUND
Authors: OBHRAI M. , LYNCH S. S. , HOLDER G. , JACKSON R. , TANG L. , BUTT W. R. 
Published: March 2008

SUMMARYEighty‐six patients were diagnosed by ultrasound to have polycystic ovaries. Twelve have fairly regular but anovular cycles (P1), 56 had oligomenorrhoea (P2) and eight had primary or secondary amenorrhoea (P3). The remaining 10 patients had raised progesterone concentrations and were excluded from the hormonal studies. Gonadotrophins, steroid hormones and sex hormone binding globulin (SHBG) were measured in all patients and the results were compared with those of 29 normal women who acted as controls. A high LH: FSH ratio was the most frequently found abnormality (raised in 68.4% of patients) followed by LH (65.8%), free testosterone (FT, calculated from total testosterone (T) and SHBG) (59.2%) and 17‐OHP (48.7%). Each of these four estimations was above the normal ranges in 25% of patients: proportionally most of the results outside the normal range occurred in group P3 followed by P2 and P1 respectively. To obtain a quantitative measure of the abnormalities, results were expressed as percentages of the mean control value for each hormone and these percentages were then summated. The four measurements, LH: FSH ratio, LH, FT and 17‐0HP gave abnormality scores ranging from a mean of 667 in P1 to 1189 in P3 compared with 405 in controls. Twenty‐one of the 76 patients were hirsute with significantly higher androgens than the non‐hirsute patients. Their mean abnormality score was 1141 compared with 855 in the non‐hirsute group and they all had at least one hormonal abnormality. The study demonstrates that there is a relationship between the degree of hormonal abnormality and the menstrual irregularities and hirsutism in women with PCOS suggesting that there may be a progressive nature to the syndrome.
MELATONIN IN INFANTS AND MOTHERS AT DELIVERY AND IN INFANTS DURING THE FIRST WEEK OF LIFE
Authors: KIVELÄ AARRE , KAUPPILA ANTTI , LEPPÄLUOTO JUHANI , VAKKURI OLLI 
Published: March 2008

SUMMARYTo evaluate the possible effect of the extreme and permanent changes in the hormonal milieu and in the lighting conditions at birth on the pineal hormone, melatonin (MT), we measured maternal vein and umbilical artery concentrations of MT in 19 parturients, post‐partum urinary concentrations of MT in 14 mothers and their infants, and daytime (0800‐2000 h) and night‐time (2000‐0800 h) urinary concentrations of MT and 6‐sulphatoxymelatonin in 22 infants during the first 8 days of life. The mean MT concentrations in maternal venous blood and umbilical arterial blood did not differ significantly from each other and there was a positive correlation between them. The same was true for postpartum urinary MT of the mothers and their infants. There was no diurnal rhythm of MT during the first week of life. MT excretion in neonates was 2‐5 pmol/12 h (only 1‐5% in comparison with adults) and that of 6‐sulphatoxymelatonin 150‐300 pmol/12 h. In reverse phase high pressure liquid chromatography (HPLC) studies, 84‐100% of total MT immunoreactivity was eluted at the same position as synthetic MT, and a small amount of hydrophobic MT‐like immunoreactive material was also detected in five of the 10 urine extracts studied. This material (perhaps a novel neonatal metabolite of MT) may be indicative of immaturity of neonatal metabolism of MT although 6‐hydroxylation is also functional in neonates. Although infant MT immediately after delivery at least partly reflects maternal MT secretion, our results show that the pineal gland is capable of producing MT at this time. However, the diurnal rhythm of MT is not yet developed, possibly because of the inability of the pineal gland to react to external stimuli at this stage, or because increased secretion of gonadotrophins after delivery suppresses the pineal gland.
GROWTH OF MALES WITH IDIOPATHIC HYPOPITUITARISM WITHOUT GROWTH HORMONE TREATMENT
Authors: VAN DER WERFF TEN BOSCH J. J. , BOT A. 
Published: March 2008

SUMMARYWe report auxologic data on 23 males with idiopathic hypopituitarism who grew up at a time when human growth hormone (GH) was not yet available, while receiving other appropriate hormonal substitution. We had reported previously that their adult heights were not significantly less than those of similar patients who had received GH. In the absence of GH the pubertal growth period was remarkably protracted, averaging 8.7 years for 19 patients during androgen substitution. Pubertal increment in height averaged 20.4 cm during induced puberty, a figure which compares favourably with those reported for GH‐treated patients. This implies that GH does not increase the height gained during pubertal growth; the increase in the rate of growth appears to be off‐set by a rise in the rate of skeletal maturation. During pubertal growth acceleration of growth of the skeleton seems unavoidably associated with acceleration of its maturation. Adult heights were significantly correlated with the heights at the time of onset of pubertal growth. This is evidence in favour of attempts to stimulate prepubertal growth much more than hitherto by earlier, higher, and more frequent doses of GH. It remains to be proved, however, that before puberty the processes of growth and maturation of the skeleton can be dissociated.
A long‐term dose‐response study of somatostatin analogue (SMS 201–995, octreotide) in resistant acromegaly*
Authors: McKnight John A. , McCance David R. , Sheridan Brian , Mcllrath Edward , Hadden David R. , Kennedy Laurence , Atkinson A. Brew 
Published: March 2008

Summary Ten acromegalic subjects were studied in a trial designed to ascertain the optimum dosage of the somatostatin analogue SMS 201–995 (octreotide) In active acromegaly. Twenty‐four‐hour growth hormone (GH) profiles were assessed monthly for 6 months and again after 1 year of continuous therapy. After basal assessment octreotide was administered subcutaneously at a dose of 100 μg three times a day throughout the first month. The dose was increased by 300 μg/day at monthly intervals to a maximum of 1500 μg/day, unless serum GH fell to within set criteria. Eight patients completed the trial. One patient withdrew because of intractable diarrhoea while another died of causes related to his acromegaly and we have no evidence that octreotide played any part in his death. Mean 24‐h GH fell from a basal level of 34·3 ± SEM 7·6 mU/I to 8·0 ± 1·3 mU/I (P > 0·05) after 6 months. At 1 month (300 μg/day) mean GH was 13·6 ± 2·2 mU/I and at 2 months (600 μg/day) 10·8 ± 2·2 mU/I (P > 0·05 vs 300 μg/day dose), and at 5 months (1500 μg/day) 11·3 ± 2·0 mU/i (all P > 0·05 vs basal). Analysis of group means revealed no significant difference between any dose schedules above 600 μg/day. After 1 year the mean GH of the group (n= 8) was 7·5 ± 1·3 mU/I (P > 0·05 vs basal). Three patients developed a deterioration and one an improvement in their glucose tolerance and three developed asymptomatic gallstones during the year of therapy. In conclusion, octreotide lowered GH levels in acromegaly over a 1‐year period. We found no evidence that routinely increasing the dose beyond 600 μg/day was helpful.
Effect of low dose iodide supplementation on thyroid function in potentially susceptible subjects: are dietary iodide levels in Britain acceptable?†
Authors: Chow C. C. , Phillips D. I. W. , Lazarus J. H. , Parkes A. B. 
Published: March 2008

Summary
objective The aim of the study was to evaluate the risk of exposure to an Increase in dietary Iodide Intake amongst potentially susceptible population groups in Britain.
design A randomized controlled trial was performed in healthy women and In women with underlying thyroid abnormalities due to subcllnical Hashimoto's thyroiditis (diagnosed on the basis of antithyroid antibodies) or previous Iodide deficiency of supplementation with 500 μg/day iodide (giving a total Intake of approximately 750 μg/day) for 28 days versus placebo.
patients Two hundred and twenty‐five women aged 25–54, randomly selected from a general practice In Cardiff, were screened for thyroid microsomal antibody. Antibody positive women (n=20), and antibody negative controls (n=30) were recruited Into the trial comparing Iodide and placebo. In addition, groups of patients aged 60–75 randomly selected from the Cardiff practice (n=29), an Iodide sufficient area, and a practice in Dowlals (n= 35), a previously iodide deficient area, were also enrolled Into the trial.
measurements Changes In free thyroxine and thyro‐trophin levels were measured after 14 and 28 days of Iodide supplementation.
results All the iodide supplemented groups responded in the same way with a small fall in free thyroxine and rise In thyrotrophin levels (combined fall In free thyroxine 14 days after the start of supplementation –1.22 (95% confidence interval – 0.59 to −1.84) pmoUl and at 28 days – 0.86 (– 0.30 to –1.43) pmol/I and rise in thyrotro‐phin at 14 days 0.55 (0.19 to 0.92) mU/I and at 28 days 0.59 (0.12 to 1.07) mU/I). In two of the iodide supplemented subjects thyrotrophin levels rose above the laboratory reference range and In a further three subjects initially elevated thyrotrophin values Increased further. In contrast, no changes In thyroid function were observed in the placebo treated controls and none developed biochemical hypothyroidism.
conclusions Dietary Iodide Intakes of 750 μg/day or more may adversely affect thyroid function, especially in individuals with borderline hypothroidism
Defects in monocyte polarization and dendritic cell clustering in patients with Graves’ disease. A putative role for a non‐specific immunoregulatory factor related to retroviral p15E
Authors: Tas M. , de Haan‐Meulman M. , Kabel P. J. , Drexhage H. A. 
Published: March 2008

SUMMARY A depressed chemotactic responsiveness of monocytes and a depressed cluster capability of dendritic cells have been found in diseases such as chronic purulent Infections of the respiratory tract and In various types of malignancies. These Impairments in monocyte and dendritic cell function could be ascribed to the action of a low molecular weight factor (LMWF; > 25 kDa) circulating In the serum of the patients. The factor, which seems to be a non‐specific Immunoregulatory factor, shares a structural homology with p15E, the capsular protein of murine and feline leukaemogenlc retroviruses. In order to study the chemotactic responsiveness of monocytes and the cluster capability of dendrltic cells of Graves’ patients, monocytes were Isolated from the peripheral blood and dendritlc cells were prepared from these peripheral blood monocytes by exposure to metrizamide. Monocytes were studied for their chemotactic responsiveness measuring their capability to polarize (morphological changes determined by light microscopy) after stimulation with the chemoattractant fMLP. Dendritic cells were studied for their capability to form clusters with allogenelc lymphocytes. A defective fMLP‐Induced monocyte polarization was found (16 vs 37% In healthy controls), whereas the dendrltic cells showed a defective clustering (60 clusters vs 151 clusters in healthy controls). The effect of fractions of > 25kDa prepared from the serum of Graves’ patients on healthy donor monocytes and dendritic cells was studied to test the presence of p15E‐like factors. The serum fractions had a significant inhibitory effect on monocyte polarization and dendrltlc cell clustering. A mixture of two monoclonal antibodies directed against p15E was able to neutralize these suppressive effects. The relationship of this p15E‐like factor occurring In the serum of Graves’ patients to the recently reported genomic expression of retroviral sequences in thyrocytes/leucocytes of Obese Strain chickens and Graves’ patients (ev 22, HIV gag) needs further clarification.