bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary Hyperaldosteronism without Suppressed Renin Due to Secondary Hypertensive Kidney Damage
Authors: Oelkers W. , Diederich S. , Bähr V. 
Published: January 2014

Abstract
Primary hyperaldosteronism is characterized by high plasma and urinary aldosterone and suppressed PRA. Renin suppression is due to aldosterone-dependent sodium retention and mild extracellular volume expansion. We observed three patients with primary hyperaldosteronism, severe refractory hypertension, and normal to high normal PRA levels whose aldosterone/renin ratios were still elevated because of disproportionately high aldosterone levels. All available medical data on the patients as well as publications on the aldosterone/renin relationship in primary hyperaldosteronism were reviewed to explain the unusual findings.
In one patient, histologically proven renal arteriolosclerosis was the probable cause of the escape of PRA from suppression by an aldosterone-producing adenoma. In the other two patients, hypertensive kidney damage due to primary hyperaldosteronism was the most likely explanation for the inappropriately high PRA, as in patient 1. All patients had high normal or slightly elevated serum creatinine levels and responded to 200 mg spironolactone/day with increased serum creatinine and hyperkalemia. Hyperkalemia was probably due to a decreased filtered load of sodium and a spironolactone-induced decrease in mineralocorticoid function. Two patients were cured of hyperaldosteronism by unilateral adrenalectomy but still need some antihypertensive therapy, whereas one patient has probable bilateral adrenal disease, with normal blood pressure on a low dose of spironolactone.
In patients with severe hypertension due to primary hyperaldosteronism, PRA can escape suppression if hypertensive kidney damage supervenes. An increased aldosterone/PRA ratio is still useful in screening for primary hyperaldosteronism. These patients may respond to spironolactone therapy with a strong increase in serum creatinine and potassium. Early specific treatment of primary hyperaldosteronism is therefore indicated, and even a patient with advanced hypertension will profit from adrenalectomy or cautious spironolactone treatment.
Measures of Bioavailable Serum Testosterone and Estradiol and Their Relationships with Muscle Strength, Bone Density, and Body Composition in Elderly Men*
Authors: van den Beld Annewieke W. , de Jong Frank H. , Grobbee Diederick E. , Pols Huibert A. P. , Lamberts Steven W. J. 
Published: January 2014

Abstract
In the present cross-sectional study of 403 independently living elderly men, we tested the hypothesis that the decreases in bone mass, body composition, and muscle strength with age are related to the fall in circulating endogenous testosterone (T) and estrogen concentrations. We compared various measures of the level of bioactive androgen and estrogen to which tissues are exposed.
After exclusion of subjects with severe mobility problems and signs of dementia, 403 healthy men (age, 73–94 yr) were randomly selected from a population-based sample. Total T (TT), free T (FT), estrone (E1), estradiol (E2), and sex hormone-binding globulin (SHBG) were determined by RIA. Levels of non-SHBG-bound T (non-SHBG-T), FT (calc-FT), the TT/SHBG ratio, non-SHBG-bound E2, and free E2 were calculated. Physical characteristics of aging included muscle strength measured using dynamometry, total body bone mineral density (BMD), hip BMD, and body composition, including lean mass and fat mass, measured by dual-energy x-ray absorptiometry.
In this population of healthy elderly men, calc-FT, non-SHBG-T, E1, and E2 (total, free, and non-SHBG bound) decreased significantly with age. T (total and non-SHBG-T) was positively related with muscle strength and total body BMD (for non-SHBG-T, respectively, β = 1.93 ± 0.52, P &lt; 0.001 and β = 0.011 ± 0.002, P &lt; 0.001). An inverse association existed between T and fat mass (β = −0.53 ± 0.15, P &lt; 0.001). Non-SHBG-T and calc-FT were more strongly related to muscle strength, BMD, and fat mass than TT and were also significantly related to hip BMD. E1 and E2 were both positively, independently associated with BMD (for E2, β = 0.21 ± 0.08, P &lt; 0.01). Non-SHBG-bound E2 was slightly strongly related to BMD than total E2. The positive relation between T and BMD was independent of E2. E1 and E2 were not related with muscle strength or body composition.
In summary, bioavailable T, E1, total E2, and bioavailable E2 all decrease with age in healthy old men. In this cross-sectional study in healthy elderly men, non-SHBG-bound T seems to be the best parameter for serum levels of bioactive T, which seems to play a direct role in the various physiological changes that occur during aging. A positive relation with muscle strength and BMD and a negative relation with fat mass was found. In addition, both serum E1 and E2 seem to play a role in the age-related bone loss in elderly men, although the cross-sectional nature of the study precludes a definitive conclusion. Non-SHBG-bound E2 seems to be the best parameter of serum bioactive E2 in describing its positive relation with BMD.
Effect of Calcium or 25OH Vitamin D3 Dietary Supplementation on Bone Loss at the Hip in Men and Women over the Age of 60*
Authors: Peacock Munro , Liu Guangda , Carey Mark , McClintock Ronald , Ambrosius Walter , Hui Siu , Johnston C. Conrad 
Published: January 2014

AbstractDietary supplements that prevent bone loss at the hip and that can be applied safely in the elderly are likely to reduce hip fractures. A daily dietary supplement of 750 mg calcium or 15 μg 25OH vitamin D3 on bone loss at the hip and other sites, bone turnover and calcium-regulating hormones were studied over 4 yr in elderly volunteers using a randomized, double-blind, placebo-controlled trial. Bone mineral density (BMD) was measured by dual x-ray absorptiometry and bone structure by radiographs. Calcium biochemistry and bone turnover markers were measured in blood and urine. The 316 women entering the trial had a mean age of 73.7 yr and the 122 men of 75.9 yr. Baseline median calcium intake was 546 mg/day, and median serum 25OH vitamin D3 was 59 nmol/L. On placebo, loss of BMD at total hip was 2% and femoral medulla expansion was 3% over 4 yr. Calcium reduced bone loss, secondary hyperparathyroidism, and bone turnover. 25OH vitamin D3 was intermediate between placebo and calcium. Fracture rates and drop-out rates were similar among groups, and there were no serious adverse events with either supplement. A calcium supplement of 750 mg/day prevents loss of BMD, reduces femoral medullary expansion, secondary hyperparathyroidism, and high bone turnover. A supplement of 15 μg/day 25OH vitamin D3 is less effective, and because its effects are seen only at low calcium intakes, suggests that its beneficial effect is to reverse calcium insufficiency.
Effects of Suckling on Hypothalamic-Pituitary-Adrenal Axis Responses to Psychosocial Stress in Postpartum Lactating Women
Authors: Heinrichs Markus , Meinlschmidt Gunther , Neumann Inga , Wagner Sabine , Kirschbaum Clemens , Ehlert Ulrike , Hellhammer Dirk H. 
Published: January 2014

In several studies lactation has been shown to be associated with a hypothalamic-pituitary-adrenal axis hyporesponsiveness to physical and psychological stressors. As it is not known whether the marked blunting of endocrine stress reactivity in women can be ascribed to suckling as a short-term effect or to lactation in general, the acute effects of suckling on the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal-medullary system responses to mental stress were investigated in lactating women.
Forty-three lactating women were randomly assigned either to breast-feed or to hold their infants for a 15-min period with the onset 30 min before they were exposed to a brief psychosocial stressor (Trier Social Stress Test). Both breast-feeding and holding the infant yielded significant decreases in ACTH, total plasma cortisol, and salivary free cortisol (all P &lt; 0.01). There were no significant differences in baseline hormone levels between the groups 1 min before the stress test. In response to stress exposure, ACTH, total plasma cortisol, salivary free cortisol, norepinephrine, and epinephrine were significantly increased in all lactating women (all P &lt; 0.001). However, total cortisol and free cortisol responses to stress were attenuated in breast-feeding women (P = 0.001 and P = 0.067, respectively), who also showed significantly decreasing PRL levels during the stress test (P = 0.005). In addition, there was no change in plasma oxytocin or vasopressin in response to the stressor. Breast-feeding as well as holding led to decreased anxiety (P &lt; 0.05), whereas, in contrast, stress exposure worsened mood, calmness, and anxiety in the total group (all P &lt; 0.001).
From these data we conclude that lactation in women, in contrast to that in rats, does not result in a general restraint of the hypothalamic-pituitary-adrenal axis response to a psychosocial stressor. Rather, suckling is suggested to exert a short-term suppression of the cortisol response to mental stress.
The Influences of Obesity and Glycemic Control on Endothelial Activation in Patients with Type 2 Diabetes
Authors: Bagg Warwick , Ferri Claudio , Desideri Giovambattista , Gamble Greg , Ockelford Paul , Braatvedt Geoffrey D. 
Published: January 2014

The aims of this study were to elucidate the factors that contribute to endothelial activation and fibrinolytic abnormalities in patients with poorly controlled type 2 diabetes and to determine whether improved glycemic control reduces endothelial activation. Adhesion molecules [E-selectin, intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1], von Willebrand factor, total nitric oxide (NO), endothelin-1, tissue plasminogen activator, and plasminogen activator inhibitor-1 were measured in 43 type 2 diabetic subjects with hemoglobin A1c of 9.0% or more at baseline (compared with 21 healthy controls) who after 20 wk had been randomized to either improved (IC) or usual (UC) glycemic control. At baseline, type 2 diabetic patients had significant endothelial activation and abnormal fibrinolysis compared with control subjects. Body mass index in the diabetic patients was the only independent predictor of E-selectin (P = 0.007), ICAM-1 (P = 0.01), and NO (P = 0.008) concentrations, but not vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, or tissue plasminogen activator (all P &gt; 0.05). Type 2 diabetic patients with a body mass index of 28 kg/m2 or less had concentrations of E-selectin, ICAM-1, endothelin-1, and NO similar to those in healthy controls. After 20 wk, hemoglobin A1c was significantly lower in IC vs. UC (IC, 8.02 ± 0.25%; UC, 10.23 ± 0.23%; P &lt; 0.0001), but there were no significant changes in markers of endothelial activation or indexes of fibrinolysis.
Obesity appears to be the most important predictor of endothelial activation in patients with type 2 diabetes. Short-term improvement in glycemic control does not appear to reduce endothelial activation.
The Complete Normalization of the Adrenocortical Function as the Criterion of Cure after Transsphenoidal Surgery for Cushing’s Disease
Authors: Estrada Javier , García-Uría José , Lamas Cristina , Alfaro José , Lucas Tomás , Diez Santiago , Salto Luis , Barceló Balbino 
Published: January 2014

Transsphenoidal microsurgery is the standard treatment for patients with Cushing’s disease. However, there is general lack of agreement regarding the definition of cure.
We studied 58 patients with corrected hypercortisolism after transsphenoidal surgery for Cushing’s disease. Plasma and urinary cortisol levels were measured after surgery. After the postsurgical hypocortisolism stage (or periodically in patients without hypocortisolism), urinary free cortisol, plasma cortisol at 0800 h and 2300 h, morning cortisol after 1 mg dexamethasone, and cortisol response to insulin-induced hypoglycemia were performed. Patients were classified in 3 groups: group I, patients with transient hypocortisolism and normal hypothalamus-pituitary-adrenal axis afterwards; group II, patients with transient hypocortisolism and abnormalities in the circadian rhythm or the stress response afterwards; and group III, patients without postoperative hypocortisolism.
Thirty-three patients were included in group I, 8 in group II, and 17 in group III. Groups I and II were similar in postsurgical plasma cortisol (46.9 ± 30.3 vs. 60.7 ± 38.6 nm) and mean follow-up (69.8 vs. 68.8 months) but were significantly different in their recurrence rate (3.4% vs. 50%, P &lt; 0.001). Patients in group III had normal postsurgical plasma and urinary cortisol but persistent abnormalities in circadian rhythm and stress response. After a mean follow-up of 39.1 months, their recurrence rate was similar to that of group II (64.7% vs. 50%).
The complete normalization of the adrenocortical function, which is always preceded by postsurgical hypocortisolism, is associated with a very low recurrence risk and should be considered, in our opinion, the main criterion of surgical cure in Cushing’s disease.
Action of Chicken II GnRH on the Human Placenta1
Authors: Siler-Khodr Theresa M. , Grayson Marcia 
Published: January 2014

The stability, receptor binding, bioactivity, and production of chicken II GnRH and its analogs in the human placenta were studied. Both chicken II and mammalian GnRH are rapidly degraded by placental enzymes, yet the chicken II isoform is six times more stable. Analogs of chicken II GnRH were synthesized, and their stability in the presence of placental enzymes was tested. The d-Arg(6)-chicken II GnRH-aza-Gly(10)-NH2 analog was found to be resistant to enzymatic degradation. The placental receptor binding activity of the chicken II GnRH analogs and chicken II GnRH was compared with that of mammalian GnRH and its analogs. Because d-Arg(6)-chicken II GnRH-aza-Gly(10)-NH2 had the highest affinity for the placental receptor and was stable in placental extracts, the bioactivity of this analog on the regulation of placental human CG (hCG) release was compared with that for mammalian and chicken II GnRH using a human term placental explant culture system. This chicken II GnRH analog effected a stimulation of hCG at the lowest concentration studied (250 nm). With extended exposure and/or higher concentrations of this chicken II GnRH analog, the release of hCG from human placental explants was inhibited. Using a placental explant perifusion system and a highly specific RIA for chicken II GnRH, the pulsatile release of chicken II GnRH from the early human placenta was demonstrated.These studies are the first to demonstrate bioactivity of a second form of GnRH in a human tissue and to identify the pulsatile release of chicken II GnRH from a human tissue. These data led us to propose that chicken II GnRH and its synthetic analogs may be potent ligands for hormone regulation during pregnancy.
Estrogen Receptor β, But Not Estrogen Receptor α, Is Present in the Vascular Endothelium of the Human and Nonhuman Primate Endometrium1
Authors: Critchley Hilary O. D. , Brenner Robert M. , Henderson Teresa A. , Williams Karin , Nayak Nihar R. , Slayden Ov D. , Millar Michael R. , Saunders Philippa T. K. 
Published: January 2014

Estrogen action is dependent upon the presence of specific ligand-activated receptors in target tissues. The aim of the present experiments was to compare the spatial and temporal pattern of expression of estrogen receptor β (ERβ) with that of ERα in full thickness endometrial samples (from the superficial to the basal zone) obtained from both women and rhesus macaques. Immunohistochemical localization with specific antibodies revealed that ERα and ERβ were both expressed in nuclei of the glands and stroma. Consistent with previous studies, expression of ERα declined in the glands and stroma of the functionalis during the secretory phase. The luminal epithelium also displayed positive immunoreactivity for ERβ. Expression of ERβ declined in glandular cell nuclei, but not stroma, within the functionalis during the late secretory phase. Levels of expression of ERα and ERβ in all cellular compartments remained unchanged in the basalis. Both receptor subtypes were detected on Western blots using proteins extracted from uterine samples obtained throughout the menstrual cycle.
There was a striking contrast between the pattern of expression of ERα and ERβ in the vascular endothelium and the perivascular cells surrounding endometrial blood vessels; only ERβ was present in the endothelial cell population, although both forms of ER were expressed in perivascular cells. We conclude that estrogen action(s) within the vascular endothelium in the endometrium may be mediated via direct binding to the ERβ isoform and that these cells could therefore be a target for agonists or antagonists that selectively target the β form of the ER.
Branched Chain Amino Acids Activate Messenger Ribonucleic Acid Translation Regulatory Proteins in Human Skeletal Muscle, and Glucocorticoids Blunt This Action1
Authors: Liu Zhenqi , Jahn Linda A. , Long Wen , Fryburg David A. , Wei Liping , Barrett Eugene J. 
Published: January 2014

Branched chain amino acids (BCAA) are particularly effective anabolic agents. Recent in vitro studies suggest that amino acids, particularly leucine, activate a signaling pathway that enhances messenger ribonucleic acid translation and protein synthesis. The physiological relevance of these findings to normal human physiology is uncertain. We examined the effects of BCAA on the phosphorylation of eukaryotic initiation factor 4E-binding protein 1 (eIF4E-BP1) and ribosomal protein S6 kinase (p70S6K) in skeletal muscle of seven healthy volunteers. We simultaneously examined whether BCAA affect urinary nitrogen excretion and forearm skeletal muscle protein turnover and whether the catabolic action of glucocorticoids could be mediated in part by inhibition of the action of BCAA on the protein synthetic apparatus.BCAA infusion decreased urinary nitrogen excretion (P &lt; 0.02), whole body phenylalanine flux (P &lt; 0.02), plasma phenylalanine concentration (P &lt; 0.001), and improved forearm phenylalanine balance (P = 0.03). BCAA also increased the phosphorylation of both eIF4E-BP1 (P &lt; 0.02) and p70S6K (P &lt; 0.03), consistent with an action to activate the protein synthetic apparatus. Dexamethasone increased plasma phenylalanine concentration (P &lt; 0.001), prevented the BCAA-induced anabolic shift in forearm protein balance, and inhibited their action on the phosphorylation of p70S6K. We conclude that in human skeletal muscle BCAA act directly as nutrient signals to activate messenger ribonucleic acid translation and potentiate protein synthesis. Glucocorticoids interfere with this action, and that may be part of the mechanism by which they promote net protein catabolism in muscle.
The Influence of Aging and Sex Hormones on Expression of Growth Hormone-Releasing Hormone in the Human Immune System1
Authors: Khorram O. , Garthwaite M. , Golos T. 
Published: January 2014

GHRH is a neuropeptide that has also been localized to the immune system. The physiological function of GHRH in the immune system has not been elucidated. This study was conducted to determine whether immune GHRH expression is altered in certain pathological states, such as immune cell tumors, and whether gender, aging, and alterations in the sex steroid milieu influence the expression of this peptide in immune cells.
Using double color flow cytometry, GHRH protein was found to be expressed in less than 2% of peripheral blood mononuclear cells (PBMC). Monocytes and B and T cells all expressed GHRH protein, although a greater percentage of T cells compared with B cells and monocytes expressed GHRH (5- to 7-fold). Semiquantitative RT-PCR was used to quantify GHRH messenger ribonucleic acid (mRNA) in PBMC and several immune cell-derived tumors. PBMC and granulocytes expressed low levels of GHRH mRNA with relatively higher levels of expression in monocytes. The tumor cell lines CEMX 174 (B/T cells), HUT 78 (T cells), WIL2-N (B cells), U937 (monocytes/macrophages), and JM 1 (pre-B cell lymphoma) all showed greater expression of GHRH mRNA relative to PBMC. However, two cell lines, CCRF-SB, a B lymphoblastoid cell line, and HL-60, a promyelocytic cell line, expressed GHRH mRNA at similar levels as PBMC.
A significant decrease in the percentage of lymphocytes (CD45+ cells) expressing GHRH protein was found in age-advanced men and women compared with young men and women. This decline was noted in B cells (CD20+) and monocytes (CD14+), but not in T cells (CD3+). GHRH mRNA expression in PBMC derived from postmenopausal women was lower than that from premenopausal women. However, no differences in PBMC GHRH mRNA expression were found in young and old men. Although in older men there were fewer peripheral lymphocytes that express GHRH protein, these cells secreted significantly more GHRH in vitro than cells from postmenopausal women with no hormone replacement therapy (HRT), but similar levels as cells from women receiving HRT. PBMC from women receiving HRT secreted more GHRH in vitro than cells from women receiving no hormone replacement.
This study demonstrates that the expression of immune GHRH is dynamic, and therefore likely to be regulated. Increased expression of GHRH in certain immune tumors suggests that GHRH may be mitogenic under certain conditions and therefore play a role in the pathogenesis of select immune cell tumors. Collectively, these results suggest a role for GHRH as a local immune modulator and in the pathophysiology of immunosenescence and immune cell tumors.
Luteal Angiogenesis: Prevention and Intervention by Treatment with Vascular Endothelial Growth Factor TrapA401
Authors: Wulff Christine , Wilson Helen , Rudge John S. , Wiegand Stanley J. , Lunn Stephen F. , Fraser Hamish M. 
Published: January 2014

The possibility of stimulating or inhibiting paracrine factors regulating angiogenesis may lead to new approaches for the treatment of pathological conditions of the female reproductive tract. We examined the effects of a clinical candidate, a soluble truncated form of the Flt-1 receptor, vascular endothelial growth factor trapA40 (VEGF trap), in a primate model to determine its ability to prevent the onset of luteal angiogenesis or intervene with the on-going process. Marmosets were treated from the day of ovulation until luteal day 3 (prevention regimen) or on luteal day 3 for 1 day (intervention regimen). Effects of VEGF inhibition were studied by obtaining a proliferation index using bromodeoxyuridine incorporation, quantifying endothelial cell area using CD31, and assessing luteal function by plasma progesterone. After both treatments, intense luteal endothelial proliferation was suppressed, a concomitant decrease in endothelial cell area confirmed the inhibition of vascular development, and a marked fall in plasma progesterone levels showed that luteal function was compromised. In situ hybridization was used to localize and quantify compensatory effects on the expression of angiogenic genes. VEGF messenger ribonucleic acid (mRNA) expression in luteal cells was increased, whereas expression of its receptor, Flt, was decreased. Inhibition of VEGF resulted in localized increased expression of angiopoietin-2 mRNA and its receptor, Tie-2.
The results show that the VEGF trap can prevent luteal angiogenesis and inhibit the established process with resultant suppression of luteal function. Luteal Flt mRNA expression is dependent upon VEGF, and VEGF inhibition results in abortive increases in expression of VEGF, angiopoietin-2, and Tie-2.