OBJECTIU: Determinar el rendiment diagnòstic de l'automesura de la pressió arterial domiciliària (AMPAd) en el diagnòstic de la hipertensió clínica aïllada (HCA) utilitzant un programa de tres dies de lectures.MATERIAL I MÈTODES: Es va incloure a cent noranta pacients diagnosticats recentment d'hipertensió lleugera-moderada no tractats, seleccionats consecutivament a 4 centres d'atenció primària de la ciutat de Barcelona. Cada pacient va realitzar lectures de AMPAd per triplicat pel matí i per la nit durant 3 dies consecutius, seguidament se'ls practicà una monitorització ambulatòria de la pressió arterial (MAPA) de 24 hores. El punt de tall de normalitat per a l'AMPAd i la MAPA diurna era de 135/85 mmHg.RESULTATS: Seixanta-tres pacients van ser diagnosticats d'HCA amb AMPAd (34.8 %; IC95%: 27.9-42.2) i 74 amb MAPA (41.6%; IC95%: 33.7-48.4). No es varen observar diferències estadísticament significatives entre els valors d'AMPAd i els de la MAPA diurna (137.4 [14.3]/82.1[8.3] mmHg vs 134.8 [11.3]/81.3[9.5] mmHg). Els paràmetres de rendiment diagnòstic de l'AMPAd van ser: S 50.0% (IC95%: 38.3-61.7), E 75.7% (IC95%: 66.3-83.2), VPP i VPN 58.7%(IC95%: 45.6-70.8) i 68.6% (IC95%: 59.4-76.7), respectivament, i CPP i CPN 2.05 i 0.66 respectivament.L'anàlisi mitjançant una corba ROC (receiver operating characteristic) dels diferents punts de tall de normalitat no va suposar l'obtenció de millores significatives en el rendiment diagnòstic de l'AMPAd.CONCLUSIONS: Un programa de 3 dies de lectures d'AMPAd en el diagnòstic de l'HCA ha obtingut una escasa precisió diagnòstica. La MAPA continúa sent la prova d'elecció en aquesta indicació. / OBJECTIVE: To determine the diagnostic performance of home blood pressure self-monitoring (hBPSM) in white-coat hypertension (WCH) using a 3-day reading program.MATERIAL and METHODS: One hundred and ninety non-treated patients recently diagnosed of mild-moderate hypertension, selected consecutively at 4 primary health-care centers in the city of Barcelona, were included. Each patient underwent morning and night hBPSM with readings in triplicate for 3 consecutive days, followed by 24-hour ambulatory blood pressure monitoring (ABPM). The normality cut-off point value for hBPSM and daytime ABPM was 135/85 mmHg.RESULTS: Sixty-three patients were diagnosed of WCH with hBPSM (34.8 %; CI95%: 27.9-42.2) and 74 with ABPM (41.6%; CI95%: 33.7-48.4). No statistically-significant differences were observed between hBPSM values and those of diurnal ABPM (137.4 [14.3]/82.1[8.3] mmHg vs 134.8 [11.3]/81.3[9.5] mmHg). hBPSM diagnostic performance parameters were: sensitivity 50.0% (CI95%: 38.3-61.7), specificity 75.7% (CI95%: 66.3-83.2), positive and negative predictive values 58.7%(CI95%: 45.6-70.8) and 68.6% (CI95%: 59.4-76.7), respectively, and positive and negative probability coefficients 2.05 and 0.66 respectively. Analysis of different normality cut-off points using a ROC curve (receiver operating characteristic) failed to produce significant improvement in the diagnostic performance of hBPSM.CONCLUSIONS: The diagnostic accuracy of a 3-day hBPSM reading program in WCH was poor. ABPM continues to be the test of choice for this indication.

INTRODUCCIÓN: La pubarquia precoz idiopática en niñas (aparición de vello púbico antes de los 8 años) se ha asociado a manifestaciones de síndrome metabólico en edad prepuberal (hiperinsulinismo, obesidad central y dislipemia), se ha relacionado con la secuencia: bajo peso al nacer, recuperación pondoestatural exagerada, desarrollo de pubarquia precoz y pubertad avanzada rápidamente progresiva y por último, se ha visto una mayor prevalencia de hiperandrogenismo ovárico (45%) en la edad adulta. La hipótesis de estudio fue que las mujeres con PP presentan manifestaciones comunes de hiperandrogenismo ovárico y síndrome metabólico en la edad adulta, siendo mayor la incidencia en las mujeres con antecedente de bajo peso al nacer y en las que no fueron tratadas con metformina en la adolescencia.METODOLOGÍA: Estudio retrospectivo, longitudinal (20 años) n= 20 mujeres (29,6 ± 3,3 años), diagnosticadas de pubarquia precoz idiopática entre 1980 y 1986, (se descartó la presencia de PP secundaria a hiperplasia suprarrenal congénita, síndrome de Cushing o tumores virilizantes) y seguidas analítica y ecográficamente hasta pasados 2 años de la menarquia, con una valoración en la edad adulta en la cual se realizó anamnesis, examen físico (peso, talla, IMC, cociente cintura/cadera), analítica (cociente neutrófilos/leucocitos, perfil lipídico, andrógenos, leptina y test de tolerancia oral a la glucosa), Ecografía pélvica (Doppler), Ecografía carotídea (Doppler) y densitometría ósea (DXA). Se realizó el estudio estadístico mediante SPSS, con significación estadística con p<0,05)RESULTADOS: 1) la prevalencia de hiperandrogenismo ovárico (criterios de Rótterdam) en las pacientes con PP fue del 35% y de síndrome metabólico del 20% (International Diabetes Federation). 2) La prevalencia de hiperandrogenismo ovárico fue mayor en la adolescencia que en la edad adulta (70% vs 35%). 3) La prevalencia de manifestaciones comunes al síndrome metabólico e hiperandrogenismo ovárico fue la siguiente: elevación del cociente neutrófilo/linfocito 70%, elevación de leptina y alteración en el metabolismo glucídico 45%, obesidad 40%, disfunción endotelial 35%, dislipemia 20% e hipertensión arterial 5%. 4) Las pacientes con pubarquia precoz presentaron mayor engrosamiento de la íntima carotídea en relación a un grupo control (n=16) de similares características con respecto a edad e IMC (0,51 ± 0,1 Vs 0,38 ± 0,07mm respectivamente) (p:0,005). 5) las pacientes con bajo peso (n=4) y peso adecuado al nacer al nacer (n=16) presentaron una prevalencia similar de hiperandrogenismo ovárico y síndrome metabólico. 6) Las pacientes que recibieron tratamiento con metformina y flutamida, iniciado durante la adolescencia y con una duración de 2 a 3 años, tuvieron una prevalencia de hiperandrogenismo ovárico menor que las pacientes que no lo tomaron (11% vs 64% respectivamente), no hubo diferencia en la prevalencia de síndrome metabólico (22% y 18%, respectivamente).CONCLUSIONES: Las pacientes con pubarquia precoz presentan alteraciones comunes al síndrome metabólico y al hiperandrogenismo ovárico en la edad adulta. Dichas alteraciones parecen ser independientes del peso al nacer, sin embargo se requiere una muestra de pacientes mayor para sacar conclusiones. El tratamiento con metformina y flutamida durante la adolescencia disminuye la incidencia de hiperandrogenismo ovárico en la edad adulta. Las pacientes con PP precisan un seguimiento clínico y analítico en la adolescencia y un control posterior en la edad adulta. / Background: Precocious pubarche in girls (PP, appearance of pubic hair before 8 yr) is associated with prepuberal hyperinsulinemia and dyslipemia, and with increased incidence of hyperinsulinemic ovarian hyperandrogenism -so called polycystic ovary syndrome (PCOS)-, at adolescence, which has been associated with endothelial dysfunction -specially with increased carotid intima-media thickness (IMT)-, and subsequent risk for cardiovascular disease and type 2 diabetes. 2) Aim and hypothesis: We hypothesized that young women with a history of PP show an increased prevalence of common manifestations for PCOS and metabolic syndrome (MS) (hyperglycaemia y/o hyperinsulinemia, dyslipemia, central adiposity, endothelial dysfunction and hypertension); PP patients small for gestational age (SGA) show a higher prevalence of PCOS and metabolic syndrome than those with adequate weight for gestational age (AGA); and women who received metformin and flutamide treatment at adolescence, have less prevalence of common manifestations of PCOS and MS at adulthood.3) Methods: A case-control study was conducted on 20 young women [age 29,6 &#61617; 3,3 yr; body mass index (BMI): 25,2 &#61617; 4,6] with a history of PP. In all cases, PP had been attributed to an amplified adrenarche, based on high circulating levels of dehydroepiandrosterona sulphate and/or androstenedione for chronological age at diagnosis. Endocrine-metabolic variables, body composition (by dual-energy X-ray absorptiometry), carotid IMT and ovarian morphology by transvaginal ultrasonography were assessed in all women.4) Results: 1) PP patients showed a 35% prevalence of PCOS (Rotterdam criteria) and a 20% prevalence of MS (International Diabetes Federation). 2) Prevalence of PCOS was higher at adolescence than at adulthood (70% vs 35%). 3) Prevalence of common manifestations for both pathologies was as follows: 45% insulin resistance and/or impaired glucose tolerance; 40% obesity, 35% endothelial dysfunction; 20% dyslipemia and 5% hypertension. 4) PP patients showed a higher carotid IMT in relation to a control group (n=16) of similar characteristics in terms of age and BMI (0,51 ± 0,1 and 0,38 ± 0,07mm, respectively) (p:0,005). 5) Patients SGA (n=4) and AGA (n=16) showed similar prevalence of PCOS and MS. 6) Patients who received metformin and flutamide treatment at adolescence (2-3 years), showed a lower prevalence of PCOS than patients who did not receive this treatment (11% and 64%, respectively), whereas the incidence of MS did not show a significant difference (22% and 18%, respectively).5) Conclusions: At adulthood, PP patients show alterations that are usually associated to MS and PCOS, independent of the weight at birth. Treatment with metformin and flutamide at adolescence decreases the incidence of PCOS at adulthood. PP patients require clinical and analytical follow-up during adolescence and a later control when they reach adulthood.

Many psychophysical studies suggest that target depth and direction during reaches are processed independently, but the neurophysiological support to this view is so far limited. Here, we investigated the representation of reach depth and direction by single neurons in an area of the medial posterior parietal cortex (V6A). Single-unit activity was recorded from V6A in two Macaca fascicularis monkeys performing a fixation-to-reach task to targets at different depths and directions. We found that in a substantial percentage of V6A neurons depth and direction signals jointly influenced fixation, planning and arm movement-related activity in 3D space. While target depth and direction were equally encoded during fixation, depth tuning became stronger during arm movement planning, execution and target holding. The spatial tuning of fixation activity was often maintained across epochs, and this occurred more frequently in depth. These findings support for the first time the existence of a common neural substrate for the encoding of target depth and direction during reaching movements in the posterior parietal cortex. Present results also highlight the presence in V6A of several types of cells that process independently or jointly eye position and arm movement planning and execution signals in order to control reaches in 3D space. It is possible that depth and direction influence also the metrics of the reach action and that this effect on the reach kinematic variables can account for the spatial tuning we found in V6A neural activity. For this reason, we recorded and analyzed behavioral data when one monkey performed reaching movements in 3-D space. We evaluated how the target spatial position, in particular target depth and target direction, affected the kinematic parameters and trajectories describing the motor action properties.

Obesity often predisposes to coronary heart disease, heart failure, and sudden death. Also, several studies suggest a reciprocal enhancing interaction between obesity and sleep curtailment. Aim of the present study was to go deeper in the understanding of sleep and cardiovascular regulation in an animal model of diet-induced obesity (DIO). According to this, Wake-Sleep (W-S) regulation, and W-S dependent regulation of cardiovascular and metabolic/thermoregulatory function was studied in DIO rats, under normal laboratory conditions and during sleep deprivation and the following recovery period, enhancing either wake or sleep, respectively. After 8 weeks of the delivery of a hypercaloric (HC) diet, treated animals were heavier than those fed a normocaloric (NC) diet (NC: 441 ±17g; HC: 557±17g). HC rats slept more than NC ones during the activity period (Dark) of the normal 12h:12h light-dark (LD) cycle (Wake: 67.3±1.2% and 57.2 ±1.6%; NREM sleep (NREMS): 26.8±1.0% and 34.0±1.4%; REM sleep (REMS): 5.7±0. 6% and 8.6±0.7%; for NC and HC, respectively; p<0.05 for all). HC rats were hypertensive throughout the W-S states, as shown by the mean arterial blood pressure values across the 24-h period (Wake: 90.0±5.3 and 97.3±1.3; NREMS: 85.1±5.5 and 92.2±1.2; REMS: 87.2±4.5 and 96.5±1.1, mmHg for NC and HC, respectively; p<0.05 for all). Also, HC rats appeared to be slightly bradycardic compared to NC ones (Wake: 359.8±9.3 and 352.4±7.7; NREMS: 332.5±10.1 and 328.9±5.4; REMS: 338.5±9.3 and 334.4±5.8; bpm for NC and HC, respectively; p<0.05 for Wake). In HC animals, sleep regulation was not apparently altered during the sleep rebound observed in the recovery period following sleep deprivation, although REMS rebound appeared to be quicker in NC animals. In conclusion, these results indicate that in the rat obesity interfere with W-S and cardiovascular regulation and that DIO rats are suitable for further studies aimed at a better understanding of obesity comorbidities.

El rápido progreso mundial en manejo y genética en vacas lecheras de alta producción, ha culminado con un aumento de animales por rebaño. A pesar de este aumento, la fertilidad y la eficacia reproductiva de estos animales ha ido disminuyendo desde los años 80. El manejo también ha sufrido importantes cambios estos años, al igual que el ambiente donde se encuentran las vacas de alta producción. La temperatura de confort de vacas lecheras se encuentra entre 5 y 25ºC, y por este motivo se puede pensar que el estrés por calor no sólo se producirá en zonas tropicales, si no que se expande globalmente y tiene una gran importancia para la ganadería. %&/El objetivo de esta tesis es estudiar factores de manejo y ambientales que puedan afectar a la fertilidad y a perdidas fetales iniciales en vacas altamente productoras en el Noreste español. Los estudios se realizaron en la zona del Segriá y los datos meteorológicos se obtuvieron de una estación situada a menos de 6 km de las granjas.En el primer estudio realizado se determinó que el índice de temperatura-humedad (THI) es mejor predictor para las perdidas fetales iniciales que la temperatura sola. Además, el período de 21-30 días postinseminación se determinó como un período crítico para la gestación.En el segundo estudio, las vacas altamente productoras fueron las que presentaron mayor fertilidad, evidenciando que el efecto negativo de la producción lechera sobre la eficacia reproductiva tiene que ser revisado. En el tercer estudio, los efectos de manejo fueron de gran importancia para la fertilidad de rebaños lecheros: el número de ordeños, los inseminadores y el toro. Posiblemente cada granja tiene que revisar periódicamente los toros utilizados, y entrenar a los técnicos inseminadotes correctamente.En el cuarto estudio se demostró que factores ambientales alrededor del periodo de inseminación tienen gran efecto sobre la fertilidad. No se pudo demostrar si el THI era mejor predictor para la pérdida de fertilidad que la temperatura sola.Finalmente en el quinto estudio se puso de manifiesto algunos marcadores de riesgo para la disminución de la fertilidad en granjas lecheras de alta producción, como los quistes ováricos y la baja producción de leche.En conclusión, para poder aumentar la eficacia reproductiva de granjas lecheras altamente productoras es necesario llevar a cabo un control periódico de los datos de cada rebaño, y monitorizar correctamente los animales. Además, el ambiente y el manejo se deben mejorar en este tipo de animales si se quiere seguir aumentando la producción lechera como hasta ahora. / The rapid worldwide progress in management and genetics of dairy herds has culminated in an increase of milk production and number of animals per herd. But despite this rapid progress, reproductive performance and reproductive disorders of high producing dairy has suffered a dramatic decrease and increase, respectively, since the mid 1980's. Management practices have also suffered significant changes during the last decades besides an increase in milk production. The most comfortable temperatures for dairy cows ranged from 5 to 25ºC. Therefore, heat stress in not confined in tropical regions of the world and has a great impact on farm economy. The main objectives of this thesis were to study environmental and management factors that affect fertility and pregnancy losses in high producing dairy cattle in northeastern Spain, a country with a seasonal warm weather. The studies were performed in high producing dairy herds in Lleida. Climatic data were obtained from a meteorological station located less than 6 km from the herds and management data were recorded in each herd.In the first study results indicated that temperature humidity index during the periimplantational period and warm season were a risk factor for pregnancy losses.In the second, cows that get pregnant before 90 days postpartum were those who produce more milk on 50 days postpartum. Management practices of these herds offset the negative effects of milk production.In the third, management practices demonstrated to be an important factor for conception rate. Three times per day milking, inseminating bull and AI technician were a risk factors for infertility.In the fourth, environment proved to be directly affecting conception rate especially around AI period.In the fifth, monthly summary records provide risk markers for fertility: low milk production and ovarian cysts.In conclusion, to increase reproductive performance of high producing dairy herds, it is necessary to monitor their status periodically. Moreover, management and environmental factors of dairy herds have a great importance on economic success of high producing dairy farms.

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The corpus luteum (CL) lifespan is characterized by a rapid growth, differentiation and controlled regression of the luteal tissue, accompanied by an intense angiogenesis and angioregression. Indeed, the CL is one of the most highly vascularised tissue in the body with a proliferation rate of the endothelial cells 4- to 20-fold more intense than in some of the most malignant human tumours. This angiogenic process should be rigorously controlled to allow the repeated opportunities of fertilization. After a first period of rapid growth, the tissue becomes stably organized and prepares itself to switch to the phenotype required for its next apoptotic regression. In pregnant swine, the lifespan of the CLs must be extended to support embryonic and foetal development and vascularisation is necessary for the maintenance of luteal function. Among the molecules involved in the angiogenesis, Vascular Endothelial Growth Factor (VEGF) is the main regulator, promoting endothelial cells proliferation, differentiation and survival as well as vascular permeability and vessel lumen formation. During vascular invasion and apoptosis process, the remodelling of the extracellular matrix is essential for the correct evolution of the CL, particularly by the action of specific class of proteolytic enzymes known as matrix metalloproteinases (MMPs). Another important factor that plays a role in the processes of angiogenesis and angioregression during the CL formation and luteolysis is the isopeptide Endothelin-1 (ET-1), which is well-known to be a potent vasoconstrictor and mitogen for endothelial cells. The goal of the present thesis was to study the role and regulation of vascularisation in an adult vascular bed. For this purpose, using a precisely controlled in vivo model of swine CL development and regression, we determined the levels of expression of the members of VEGF system (VEGF total and specific isoforms; VEGF receptor-1, VEGFR-1; VEGF receptor-2, VEGFR-2) and ET- 1 system (ET-1; endothelin converting enzyme-1, ECE-1; endothelin receptor type A, ET-A) as well as the activity of the Ca++/Mg++-dependent endonucleases and gelatinases (MMP-2 and MMP-9). Three experiments were conducted to reach such objectives in CLs isolated from ovaries of cyclic, pregnant or fasted gilts. In the Experiment I, we evaluated the influence of acute fasting on VEGF production and VEGF, VEGFR-2, ET-1, ECE-1 and ET-A mRNA expressions in CLs collected on day 6 after ovulation (midluteal phase). The results indicated a down-regulation of VEGF, VEGFR-2, ET-1 and ECE-1 mRNA expression, although no change was observed for VEGF protein. Furthermore, we observed that fasting stimulated steroidogenesis by luteal cells. On the basis of the main effects of VEGF (stimulation of vessel growth and endothelial permeability) and ET-1 (stimulation of endothelial cell proliferation and vasoconstriction, as well as VEGF stimulation), we concluded that feed restriction possibly inhibited luteal vessel development. This could be, at least in part, compensated by a decrease of vasal tone due to a diminution of ET-1, thus ensuring an adequate blood flow and the production of steroids by the luteal cells. In the Experiment II, we investigated the relationship between VEGF, gelatinases and Ca++/Mg++-dependent endonucleases activities with the functional CL stage throughout the oestrous cycle and at pregnancy. The results demonstrated differential patterns of expression of those molecules in correspondence to the different phases of the oestrous cycle. Immediately after ovulation, VEGF mRNA/protein levels and MMP-9 activity are maximal. On days 5–14 after ovulation, VEGF expression and MMP-2 and -9 activities are at basal levels, while Ca++/Mg++-dependent endonuclease levels increased significantly in relation to day 1. Only at luteolysis (day 17), Ca++/Mg++-dependent endonuclease and MMP-2 spontaneous activity increased significantly. At pregnancy, high levels of MMP-9 and VEGF were observed. These results suggested that during the very early luteal phase, high MMPs activities coupled with high VEGF levels drive the tissue to an angiogenic phenotype, allowing CL growth under LH (Luteinising Hormone) stimulus, while during the late luteal phase, low VEGF and elevate MMPs levels may play a role in the apoptotic tissue and extracellular matrix remodelling during structural luteolysis. In the Experiment III, we described the expression patterns of all distinct VEGF isoforms throughout the oestrous cycle. Furthermore, the mRNA expression and protein levels of both VEGF receptors were also evaluated. Four novel VEGF isoforms (VEGF144, VEGF147, VEGF182, and VEGF164b) were found for the first time in swine and the seven identified isoforms presented four different patterns of expression. All isoforms showed their highest mRNA levels in newly formed CLs (day 1), followed by a decrease during mid-late luteal phase (days 10–17), except for VEGF182, VEGF188 and VEGF144 that showed a differential regulation during late luteal phase (day 14) or at luteolysis (day 17). VEGF protein levels paralleled the most expressed and secreted VEGF120 and VEGF164 isoforms. The VEGF receptors mRNAs showed a different pattern of expression in relation to their ligands, increasing between day 1 and 3 and gradually decreasing during the mid-late luteal phase. The differential regulation of some VEGF isoforms principally during the late luteal phase and luteolysis suggested a specific role of VEGF during tissue remodelling process that occurs either for CL maintenance in case of pregnancy or for noncapillary vessel development essential for tissue removal during structural luteolysis. In summary, our findings allow us to determine relationships among factors involved in the angiogenesis and angioregression mechanisms that take place during the formation and regression of the CL. Thus, CL provides a very interesting model for studying such factors in different fields of the basic research.

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