Browsing by Author "FORADORI, A"

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    A PREPUBERTAL SURGE OF THYROTROPIN PRECEDES AN INCREASE IN THYROXINE AND 3,5,3'-TRIIODOTHYRONINE IN NORMAL-CHILDREN
    (ENDOCRINE SOC, 1991) MICHAUD, P; FORADORI, A; RODRIGUEZPORTALES, JA; ARTEAGA, E; LOPEZ, JM; TELLEZ, R
    The variations in plasma levels of TSH, T4, T3, and rT3, during the pubertal period, were studied in 647 school students from the urban area of Santiago in Chile (47% males and 53% females) with ages ranging between 7.5 and 15 yr. The subjects were grouped by age in consecutive intervals of 6 months each, and pubertal development was determined in every subject. TSH showed a significant increase, reaching a peak in the 9- to 9.5-yr interval. The same was found for T3 and T4, which reached a peak by 10 and 11 yr. The T4/T3 ratio did not show any significant variation with age. After 9.5 yr, a decrease in rT3 and increase in the T4/rT3 ratio was found. The TSH peak preceded the onset of clinical pubertal development, while the T3 and T4 peaks coincided with this onset. The variations in rT3 suggest an increase of peripheral conversion of T4 to T3. These transient events, not described until now, could be termed thyroidarche and could have a significant effect on pubertal growth and development.
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    COMPARATIVE-STUDY OF SIZE, TOTAL PROTEIN, FIBRINOGEN AND 5-HT CONTENT OF HUMAN AND CANINE PLATELET DENSITY SUBPOPULATIONS
    (1986) MEZZANO, D; ARANDA, E; FORADORI, A
    The size, total protein, fibrinogen and 5-HT content were evaluated in density subpopulations of human and canine platelets fractionated in linear arabinogalactan gradients. The methodology was assessed to ascertain that platelet separation was by density and to discard artifactual changes and platelet release during the procedure. EDTA or PGE1 increased the size of human PRP-platelets, but not of dog platelets. In humans, high density (HD) platelets were 1.26 times larger and contained 1.88 times more fibrinogen, 2.23 times more 5-HT and 1.37 times more protein than low density (LD) platelets; in dogs, these density cohorts did not differ in protein content, but LD platelets were 1.29 times larger and had 1.33 times more fibrinogen and 5-HT than HD platelets. These findings suggest that cell density is mostly dependent on the protein content per unit volume of platelets (and not on dense bodies). The differences in fibrinogen and 5-HT content between HD and LD cohorts in humans and dogs may be related to platelet age. The difference in volume between HD and LD platelets in dogs is of uncertain interpretation.
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    EFFECT OF MATERNAL ADMINISTRATION OF THYROTROPIN-RELEASING-HORMONE ON THE PRETERM FETAL PITUITARY-THYROID AXIS
    (1991) MAYA, F; MENA, P; FORADORI, A; BECERRA, M; INZUNZA, A; GERMAIN, A
    We evaluated the response of preterm fetuses to maternal intravenous injection of 400-mu-g of thyrotropin releasing hormone (TRH) between 30 minutes and 5 hours before delivery (n = 12). An additional seven mothers received saline solution and served as control subjects. There were no statistically significant differences in gestational age, birth weight, or Apgar scores between groups. At delivery, concentrations of maternal thyrotropin were elevated in the TRH group compared with the control group (12.0 +/- 1.6 vs 5.6 +/- 0.5 mU/L; p < 0.005); however, maternal triiodothyronine (T3) values remained unchanged. Significant elevations of fetal thyrotropin and T3 were observed after maternal administration of TRH compared with control subjects (45.8 +/- 7.7 vs 8.4 +/- 0.9 mU/L (p < 0.002) and 1.3 +/- 0.07 vs 0.7 +/- 0.04 nmol/L or 87 +/- 5 vs 49 +/- 3 ng/dl (p < 0.001), respectively). Fetal thyroxine (T4) and prolactin values were also elevated after exposure to TRH (135 +/- 5 vs 86 +/- 10 nmol/L or 10.5 +/- 0.4 vs 6.7 +/- 0.8-mu-g/dl (p < 0.001) and 212 +/- 31 vs 105 +/- 28-mu-g/L (p < 0.05), respectively). Two hours after birth, a significant increase in T3 but not T4 levels was observed in both groups of infants. These data indicate that fetal exposure to a single dose of TRH via maternal administration of this hormone results in marked stimulation of the preterm fetal pituitary-thyroid axis, as in the fetus at term, and that this treatment does not inhibit the early postnatal surge of T3.
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    KINETICS OF PLATELET DENSITY SUBPOPULATIONS IN SPLENECTOMIZED MONGREL DOGS
    (1984) MEZZANO, D; ARANDA, E; FORADORI, A; RODRIGUEZ, S; LIRA, P
    Autologous 51Cr-platelet kinetic studies were performed in splenectomized mongrel dogs. Mean survival time of PRP[platelet-rich plasma]-platelets was 5.4 .+-. 1.5 (SD) days (n = 6). The curves, though slightly curvilinear, showed mostly a linear type of decay, denoting that platelet removal from the circulation is mainly determined by aging of the cells. High-density (HD) and low-density (LD) platelet cohorts were isolated in Stractan gradients from samples drawn daily after infusion of labeled platelets. Specific radioactivity in HD cohorts declined rapidly postinfusion (T1/2 [half-life] = 1.3 days), but specific radioactivity in LD platelets increased for 2 days and steadily declined for 4 days thereafter (n = 6). Labeled HD platelets, comprising 11.7% of the total population, lived significantly longer in circulation than LD platelets (19.1% of the total population) (n = 3). The patterns of decay of the radioactivity do not have all the characteristics of pure age-cohort survival curves; 3.7 days after the infusion of labeled HD platelets, the specific radioactivity in LD cohorts was 6 times higher than on day 1, but attained only 20% of the initial specific radioactivity in HD platelets. After the infusion of labeled LD platelets no radioactivity was recovered in circulating HD cohorts. Mongrel dog platelets apparently decrease in density with aging, but also platelet density heterogeneity is in part determined during the thrombopoietic process. These data are consistent with those of other authors in rabbits and rhesus monkeys, but contrast with the observations that platelets in humans, baboons and Macaca fasicularis monkeys increase in density with age, suggesting that the displacement of platelets toward compartments of either higher or lower density depends on the species under study.
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    MONITORING OF CYCLOSPORINE BLOOD-LEVELS WITH POLYCLONAL AND MONOCLONAL ASSAYS DURING EPISODES OF RENAL GRAFT DYSFUNCTION
    (1989) MARTINEZ, L; FORADORI, A; VACCAREZZA, A; MARTINEZ, P; RODRIGUEZ, L
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    PLATELET 5-HYDROXYTRYPTAMINE INCREASES WITH PLATELET AGE IN DOGS
    (GEORG THIEME VERLAG KG, 1991) MEZZANO, D; DELPINO, GE; MONTESINOS, M; GARCIA, ME; ARANDA, E; FORADORI, A
    Thrombocytopenia was induced in mongrel dogs by two mechanisms: immunologically, by intravenous injection of heterologous antiplatelet antibody, and non-immunologically, by circulating the blood through glass beads in anesthetized animals. The platelet content of 5-HT was monitored before and during the recovery of the blood platelet counts. This period is associated with the normalization of the mean platelet survival time and with a progressive increase in the mean age of the circulating platelet population. A continuous increment in platelet 5-HT closely followed the increase in platelet counts in both models of thrombocytopenia, and a strong correlation was found between the platelet age and 5-HT content. These findings support the concept that platelets accumulate 5-HT during their physiological aging process, contradicting the notion that a negative balance in 5-HT content results at the end of their physiological lifespan in circulation. These results are not in conflict with the concept that circulating platelets release and re-uptake 5-HT.
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    RESPONSE OF THE MATERNAL, FETAL, AND NEONATAL PITUITARY-THYROID AXIS TO THYROTROPIN-RELEASING-HORMONE
    (1986) MOYA, F; MENA, P; HEUSSER, F; FORADORI, A; PAIVA, E; YAZIGI, R; MICHAUD, P; GROSS, I
    Thyrotropin releasing hormone (TRH) readily crosses the placenta and stimulates the fetal pituitary. We studied the response of the maternal and fetal pituitary-thyroid axes to TRH and the influence of prenatal exposure to TRH on the physiological postnatal increase in thyrotropin (TSH) and triiodothyronine (T3) in the neonate. Twenty-six pregnant women received TRH (400 or 600 .mu.g) intravenous or saline (controls) either 2 or 12 h before elective cesarean section at term. Administration of 400 .mu.g of TRH resulted in significant elevations of maternal TSH (15.7 .+-. 2.9 versus 3.2 .+-. 0.4 .mu.U/ml, p < 0.01) and prolactin (416 .+-. 94 versus 223 .+-. 41 ng/ml, p < 0.05) 2 h later. Maternal T3 remained unchanged. A higher dose of TRH (600 .mu.g) produced comparable results. Maternal administration of TRH (400 .mu.g) 2 h before delivery resulted in significant increases in fetal TSH and T3 over controls (21.1 .+-. 3.7 versus 4.8 .+-. 1.0 .mu.U/ml, and 132 .+-. 12 versus 64 .+-. 9 ng/dl, p < 0.01, respectively). Cord blood hormone levels 12 hours after TRH administration were similar to controls. Higher doses of TRH did not produce further increases in fetal TSH or T3. Control and treated neonates demonstrated similar physiological postnatal increases in TSH and T3, suggesting that prior exposure to TRH did not blunt this response. These data suggest that maternal administration of TRH is an effective way of increasing fetal T3 levels, and that this treatment does not inhibit the postnatal surge is TSH and T3.
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    UTERINE KALLIKREIN IN THE EARLY PREGNANT RAT
    (OXFORD UNIV PRESS INC, 1993) VALDES, G; CORTHORN, J; SCICLI, AG; GAETE, V; SOTO, J; ORTIZ, ME; FORADORI, A; SAED, GM
    Uterine homogenates of cycling and early pregnant Sprague Dawley rats and purified rat urinary kallikrein showed similar curves of displacement of I-125-kallikrein binding to a polyclonal antibody. Uterine kallikrein concentration measured by RIA was 8.7 +/- 2 SEM ng/g wet weight during the cycle (n = 6 in diestrus and metestrus) and 20.8 +/- 2 SEM (n = 7) ng/g wet weight on Day 7 of pregnancy (P7) (p < 0.001). On P7, kallikrein concentration was increased 12.4-fold in the implantation nodes, as compared to the interimplantation segments. Uterine homogenates of rats on P7, submitted to DEAE-cellulose chromatography and Sephadex gel filtration, yielded two fractions containing kallikrein immunoreactivity and kininogenase activity, with molecular masses that ranged from 120-125 kDa and 39-43 kDa, respectively. In the RIA, both fractions displayed parallelism with purified kallikrein. Enzymatic activity was expressed after activation by trypsin. It was inhibited by aprotinin, PMSF, p-amino-benzamidine, and leupeptin, but not by soybean or ovomucoid trypsin inhibitors. Kallikrein mRNA was demonstrated by reverse transcriptase/polymerase chain reaction in uteri of nonpregnant and P7 rats. These results show that rat uterus synthesizes one or more serine proteases that are immunologically and enzymatically related to tissue kallikrein. The increase of kallikrein in the implantation node on P7-determined both by an increment of whole uterus kallikrein content and a depletion of the interimplantation segments-suggests that kallikrein may play a role in the vasoactive changes of implantation.