The very high carrier frequency of 21-hydroxylase deficiency worldwide has been postulated as indicating a survival advantage. The 'mediators' of such an effect remain speculative.To look for possible differences in the metabolic and atherogenic risk profile of carriers and noncarriers of CYP21A2 gene mutations at puberty in order to identify possible mediators of the presumed survival advantage for the carriers. It is anticipated that by studying atherogenic risk factors at such an early developmental stage, age-related alterations in these factors may be minimized.The study group included 45 adolescent girls diagnosed in our center with premature pubarche, 29 of whom were noncarriers and 16 carriers of CYP21A2 mutations. The two groups did not differ in chronological age, age at pubarche or menarche, pubertal stage, body mass index and waist-to-hip ratio. Biochemical and hormonal profile markers as well as markers of endothelial dysfunction were determined by appropriate methodology. Additionally, in each subject, an oral glucose tolerance test and a gonadotrophin-releasing hormone GnRH analogue stimulation test were carried out.Endothelin-1 values were lower in the carriers compared to the noncarriers (p = 0.031). Higher tissue plasminogen activator and lower plasminogen activator inhibitor-1 values were found in carriers compared to noncarriers (p = 0.02 and <0.001, respectively). The ratio of the insulinogenic index/homeostasis model assessment for insulin resistance, which reflects beta-cell function, was higher in carriers (p = 0.048), indicating a more favorable beta-cell function in the carriers.Our findings that carriers of CYP21A2 gene mutations have a more favorable internal milieu with regard to the metabolic syndrome and atherogenesis support the theory that heterozygous CYP21A2 mutations provide a survival advantage. The mechanisms involved may be related to the insulin secretion-action pathway, hypothalamic-pituitary-adrenal axis responsiveness or other still unrecognized factors.
This chapter addresses the dynamic response of single-degree-of-freedom (SDOF) oscillators in the linear elastic domain, with emphasis on ground-induced excitation. It develops the equation of motion, discusses solution approaches and presents the representation of response using pseudo-acceleration, velocity, and displacement spectra. The equations governing structural dynamics are easily established based on Newton's first two laws of motion. The momentum of a body is a vector quantity given by the product of mass and velocity. Resonance is the tendency of a system to oscillate with large peak amplitude under forced vibration at particular frequencies, known as the system's resonant frequencies. Earthquake ground motion is conveniently defined by acceleration records obtained in three orthogonal directions from a seismograph. The time derivative of the relative displacement time history is the relative velocity time history; its time derivative is the relative acceleration time history.
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A procedure is presented for deriving low‐complexity structural models to predict the global response of asymmetric‐plan low‐rise frame buildings for purposes of class‐level assessment. As a compromise between employing a full‐scale multi‐degree‐of‐freedom structural model versus an equivalent single‐degree‐of‐freedom one, the challenge is to create an idealized 3D structure with few degrees‐of‐freedom that can match the inelastic response of a building for which full knowledge of geometrical and mechanical properties is available. Such a 3D reduced‐order model can offset the computational cost related to performing multiple nonlinear dynamic analyses within the framework of Performance‐Based Earthquake Engineering. To this goal, rules and equations are proposed for achieving equivalence among the linear and nonlinear properties (e.g. mass, stiffness, strength) of the building analysed and the related 3D reduced‐order model. The procedure is applied on a sample of 15 existing reinforced‐concrete frame school buildings, from the province of Foggia in Southern Italy, for which the full numerical models are available. Both calibrated and uncalibrated reduced‐order models are created, exploring the limitations of the proposed order‐reduction in a real‐life case study.
The antiglucocorticoid steroid, RU 486, elevated plasma ACTH concentrations when administered im at 0700 h in a dose of 1.0 mg/kg in nonhuman primates (Macacafascicularis; P < 0.05). The duration, but not the magnitude, of this response increased after 5.0 mg/kg RU 486 im; release of ACTH did not rise further after 10 mg/kg. Peak ACTH elevations occurred 1−2 h after RU 486 administration. Plasma cortisol concentrations peaked 4 h after RU 486 administration and the response was significant only after 5.0 mg/kg RU 486. Plasma arginine vasopressin (AVP) concentrations also increased after RU 486 but the increase occurred only after the 10.0 mg/kg dose {P < 0.05). The AVP elevation was greatest 4 h after 10 mg/kg RU 486 and was abolished by dexamethasone pretreatment. We conclude that: 1) RU 486 elevates plasma ACTH, cortisol,and AVP concentrations in a manner which is both dose and time dependent, 2) ACTH releaseoccurred at an order of magnitude lower dose than did AVP release, and 3) plasma AVP changes after RU 486 are glucocorticoid dependent.
