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A. Parra, A. Ramírez del Angel, C. Cervantes and M. Sánchez

Abstract.

The daily urinary excretion of dopamine (DA), noradrenaline (NA) and adrenaline (A) was investigated in 43 clinically healthy males and 37 females, aged 13 days to 37.5 years. There was a progressive increase in the daily output of each catecholamine (μg/24 h) with increasing age (P < 0.025 to < 0.001), and the opposite was seen when values were expressed as μg/g creatinine (P < 0.05 to < 0.025). However, when values were expressed as μg/m2/24 h no significant differences were disclosed among the different age groups, except for a transient rise in DA excretion in the group 1.0–4.9 years. A significant linear correlation was observed between chronological age and urinary DA (r = 0.814, P < 0.05), NA (r = 0.837, P < 0.05) and A (r = 0.839, P < 0.05), and also between body weight and each one of the catecholamines (DA: r = 0.731, P < 0.05; NA: r = 0.839, P < 0.05; A: r = 0.720, P < 0.05). However, a quadratic correlation existed between height and DA (r = 0.759, P < 0.05), NA (r = 0.853, P < 0.05) and A (r = 0.814, P < 0.05). Each one of these models could explain up to 73% of the observed variability. It is suggested that: a) the most convenient form to express the daily urinary excretion of catecholamines is as μg/m2/24 h; b) the excretion of these compounds increased at a faster rate approximately after 130.0—135.0 cm of height; c) this height-related greater increase in the output of catecholamines occurs simultaneously with previously reported increases in haemoglobin and haematocrit and significant changes in plasma concentrations of thyroid hormones; d) although the mechanisms involved in these changes remain to be clarified, it is interesting to note that they occur at a time when oxygen requirements are greater consecutive to the rapid increase of lean body tissues.

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J. M. de Gandarias, L. Casis, J. Irazusta, E. Echevarría, G. Arechaga and M. Ramírez

Abstract.

Peptidase enzymes are involved in neuropeptide processing or degradation. In order to analyse a possible functional participation of these enzymes, arylamidase activity of several rat brain regions and serum was assayed in the soluble fraction during the estrous cycle using L-Lys- and L-Tyr-β-naphthylamide as substrates. Significant differences were present in the hypothalamus, the pituitary and serum when both substrates were used. However, there were no differences in cortical areas. These results suggest a role for arylamidase activity in the hormonal changes that happen during the estrous cycle of the rat.

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M. Ramirez, B. Sanchez, G. Arechaga, S. Garcia, P. Lardelli, D. Venzon and J. M. de Gandarias

Abstract.

The thyroliberin and luliberin contents exhibit a diurnal rhythm within the brain and an asymmetrical distribution of both neuropeptides has been demonstrated in the hypothalamus. Since they have been described as substrates of pyroglutamyl peptidase I, this activity was analysed in several rat brain regions and other structures, in order to investigate its putative diurnal variations and changes in relation to the distribution of these neuropeptides and/or other susceptible substrates. Fluorometric activity was assayed in the retina, pituitary gland, superior cervical ganglia, pineal gland, some selected brain regions, and serum of adult male rats at six different time points of a 12:12 h light:dark cycle, using pyroglutamyl-β-naphthylamide as substrate. A significant circadian rhythm was demonstrated in the retina, the hypothalamus, and the intermediate-posterior pituitary lobe. In addition, a small but significant asymmetrical distribution of this activity, at certain time points, was disclosed: The activity was higher in the left than in the right retina at 10 h of the light period, whereas it was predominant in the right side at 01 h of the dark period. Furthermore, the activity was higher in the left anterior than in the right hypothalamic area at 13 and 01 h. These results could be indicative of a role of this enzymatic activity in the control of the functional status of its endogenous substrates.

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P. Pujol-Amat, J. Urgell-Roca, J. Esteban-Altirriba, M. Márquez-Ramirez and J. Hernández- Soler

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Jorge R. Ferraris, Horacio M. Domene, Maria E. Escobar, Maria G. Caletti, Jose A. Ramirez and Marco A. Rivarola

Abstract. The effects of chronic renal failure on the hypothalamic-pituitary-ovarian axis in 25 girls, aged 9.1 to 20.9 years (mean 13.8) were studied. Twelve patients on conservative treatment (group A) had serum creatinine values between 176.8 and 1502.8 μmol/l; 9 patients were on haemodialysis (group B); and 12 patients had received a renal transplant (group C). Tanner stage of breast development was delayed relative to chronological age in 5 out of 18 patients. Serum oestradiol was normal or low when related to pubertal stages in all groups. Serum LH was elevated in group A and B patients, but normal in group C patients. Serum FSH was elevated in 6 out of the 21 patients in group A plus B, and in 2 out of the 12 patients in group C. Serum PRL was elevated in 12/12, 6/8, and 4/11 patients in group A, B, and C respectively. After GnRH administration to 4 patients in group A, 3 showed delayed or absent gonadotropin response; all 4 patients studied in group C showed normal gonadotropin response. The data indicate a decreased E2 secretion, abnormal gonadotropin and PRL levels and a blunted gonadotropin response to GnRH in girls with chronic renal failure. These results seem to indicate an alteration of the hypothalamic-pituitary unit that can be reversed after successful renal transplantation.

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Manuel Luque-Ramírez, Covandonga Mendieta-Azcona, José M del Rey Sánchez, Milagro Matíes and Héctor F Escobar-Morreale

Objective

To study the blood clotting tests and endothelial function of polycystic ovary syndrome (PCOS) patients and non-hyperandrogenic women, and their changes during PCOS treatment, as a function of the presence of obesity and smoking.

Design

Case-control study followed by a randomized clinical trial.

Methods

Blood clotting and endothelial function were analyzed in 40 PCOS patients and 20 non-hyperandrogenic women. Thirty-four PCOS women were randomized to an oral contraceptive containing 35 μg ethinyl-estradiol plus 2 mg cyproterone acetate (Diane35Diario) or metformin (850 mg twice daily), monitoring the changes on these parameters during 24 weeks of treatment. The influence of obesity and smoking was also analyzed.

Results

Blood clotting and endothelial function tests were similar among PCOS patients and controls with the exception of a higher platelet count in the former. Obesity increased circulating fibrinogen levels, prothrombin activity and platelet counts, and reduced prothrombin and activated partial thromboplastin times. Smoking increased fibrinogen levels, platelet counts, and prothrombin activity, and reduced prothrombin time, in relation to the larger waist circumference of smokers. Irrespective of the treatment received, PCOS patients showed a decrease in prothrombin time and an increase in prothrombin activity, with a parallel increase in homocysteine levels in metformin users. The activated partial thromboplastin time decreased markedly in the patients treated with Diane35Diario. Finally, flow-mediated dilation improved in non-smokers irrespective of the drug received, but worsened in smokers.

Conclusions

Oral contraceptives and metformin may exert deleterious effects on blood clotting tests of PCOS women, yet the effects of metformin appear to be milder. Because smoking potentiates some of these effects and deteriorates endothelial function, smoking cessation should be promoted in PCOS patients.

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Anna Aulinas, María-José Ramírez, María-José Barahona, Elena Valassi, Eugenia Resmini, Eugènia Mato, Alicia Santos, Iris Crespo, Olga Bell, Jordi Surrallés and Susan M Webb

Introduction

Hypercortisolism in Cushing's syndrome (CS) is associated with increased morbidity and mortality. Hypercortisolism also occurs in chronic depressive disorders and stress, where telomere length (TL) is shorter than in controls. We hypothesized that shortening of telomere might occur in CS and contribute to premature aging and morbidity.

Aim

To investigate TL in CS patients compared with controls.

Methods

Seventy-seven CS patients (14 males, 59 pituitary, 17 adrenal, and one ectopic; 21 with active disease) were compared with 77 gender-, age-, and smoking-matched controls. Fifteen CS were evaluated longitudinally, during active disease and after remission of hypercortisolism. Leukocyte TL was measured by telomere restriction fragment–Southern technique. Clinical markers were included in a multiple linear regression analysis to investigate potential predictors of TL.

Results

Mean TL in CS patients and controls was similar (7667 vs 7483 bp, NS). After adjustment for age, in the longitudinal evaluation, TL was shorter in active disease than after remission (7273 vs 7870, P<0.05). Age and dyslipidemia were negative predictors (P<0.05), and total leukocyte count was a positive predictor for TL (P<0.05). As expected, a negative correlation was found between TL and age (CS, R=−0.400 and controls, R=−0.292; P<0.05). No correlation was found between circulating cortisol, duration of exposure to hypercortisolism or biochemical cure and TL.

Conclusion

Even though in the cross-sectional comparison of CS and controls no difference in TL was found, in the longitudinal evaluation, patients with active CS had shorter TL than after biochemical cure of hypercortisolism. These preliminary results suggest that hypercortisolism might negatively impact telomere maintenance. Larger studies are needed to confirm these findings.