PubMed Health⌕ Search

Biomedical subjects

R Calvo

Publications and source records attributed to R Calvo.

At least 55 records · Page 3Linked to original sources
PubMed1994

Thyroxine treatment and the recovery of pyramidal cells of the cerebral cortex from changes induced by juvenile-onset hypothyroidism.

In contrast to the permanent alterations resulting from neonatal hypothyroidism, the effects of juvenile-onset hypothyroidism on the number and distribution of spines along the apical shaft of pyramidal neurons of the visual cortex appeared to be potentially reversible with adequate thyroxine (T4) therapy (Ruiz-Marcos et al., 1980, Brain Res. 185:91-102 and 1982, Brain Res. 239:559-574). Treatment with 0.20 or 1.50 micrograms T4/100 g body weight per day had, however, only partially reversed the changes induced by juvenile-onset hypothyroidism. We here study whether or not a higher dose of T4 would totally reverse these effects. A group of rats were thyroid-ectomized at 40 days of age, and injected once daily with placebo or T4 (1.75 micrograms/100 g BW per day) from 70 to 90 days of age, a group on 1.50 micrograms being included to compare with previous results. Spine number and distribution were measured, as well as the concentrations of T4 and triiodothyronine (T3) in plasma, liver and brain. The activities of two hepatic enzymes were measured as thyroid hormone-sensitive biological end points. The 1.75-micrograms dose restored spine number to 88% of normal values and was markedly more effective than the 1.50-micrograms dose, which increased it to 68%. The degree of restoration appeared related to the concentration of T3. It is concluded that the changes caused by juvenile-onset hypothyroidism in the number and distribution of dendritic spines along the apical shafts of pyramidal neurons are reversible, although complete restoration might require a higher dose of T4, a continuous mode of administration, or longer period of treatment.

Age of Onset↗
PubMed1994

Decrease in penbutolol protein binding as a consequence of treatment with some alkylating agents.

The effect of in vitro treatment of serum with the alkylating agents carmustine (BCNU) and mechlorethamine on the protein binding of penbutolol, a basic agent mainly bound to alpha 1-acid glycoprotein (AAG), was investigated. The free fraction of penbutolol increased significantly (P < 0.001) after the treatment of serum with BCNU (5.27+ +/- 0.47%) and with mechlorethamine (5.23% +/- 0.17%), being 1.98% +/- 0.18% in serum not treated with BCNU or mechlorethamine. In addition, after incubation with BCNU (2 h), the free fraction of penbutolol continued increasing (10.96% +/- 0.70% vs 5.27% +/- 0.47% at time 0; P < 0.001), whereas it remained unchanged after incubation with mechlorethamine. Moreover, dialysis against saline for 24 h did not restore the free fraction of penbutolol, which increased after treatment with carmustine (9.05% +/- 1.24% vs. 11.04% +/- 1.55%, nondialyzed). We concluded that the treatment of cancer patients with alkylating agents could alter the serum proteins and modify their binding capacity, and this should be taken into account in the simultaneous treatment of these patients with other basic drugs like penbutolol, e.g., methadone.

Adult↗
PubMed1994

Regional thyroid hormone levels in rat brain.

Levels of T4 and T3 were measured in half-brain and seven brain regions. Although thyroid hormones were distributed throughout the brain, T4 levels were highest in cerebellum and thalamus. The highest T3 levels were observed in the thalamus and lowest levels were found in olfactory bulb, hypothalamus, and amygdala.

Animals↗
PubMed1994

Effects of thyroid hormone deiodination on regulation of thyroid axis in undernourished rats.

The possible influence of hypothalamic and pituitary 5'-deiodinase II (5'-D-II) activity and 3,5,3'-triiodothyronine (T3) content on the modulation of thyroid-stimulating hormone (TSH) synthesis was studied. 1) Alterations in 5'-D-II activity and hypothalamic and pituitary T3 content produced by undernutrition were observed in fetal (21 days) and neonatal rats vs. controls. 2) After thyroidectomy, plasma TSH increased in both populations, undernourished and control, but pituitary TSH increased only in the former and not in the latter. The results obtained by giving small doses of thyroxine (T4; 0.5 micrograms/100 g body wt) to intact and thyroidectomized rats suggest a lower inhibitory effect by T4 on the pituitary in undernourished than in control rats. Although hypothalamic and pituitary 5'-D-II activity increased in both groups after thyroidectomy, the percentage increase was lower in undernourished vs. control rats, resulting in lower overall T3 content in tissues from undernourished animals. These studies on thyroid axis regulation show the in vivo regulation of TSH synthesis by hypothalamic and pituitary 5'-D-II activity and T3 content.

Animals↗
PubMed1994

Thyroid hormones in tissues from fetal and adult rats.

Concentrations of T4 and T3 were recently measured in rat fetal tissues, and the reported values were found to be more than 10-fold higher than those found by us. The differences have been explained by the assumption that previous analytical procedures, neither avoid deiodination during autopsy of the animals or during extraction and purification, because phloretin [(3'),4',4,6-(tetra)trihydroxyaurone], a potent inhibitor of 5'-iodothyronine deiodinase activity in vitro, had not been used to prevent such problems. We here show that perfusion with phloretin during autopsy does not affect 5'-iodothyronine activity or T4 and T3 concentrations in liver, kidney, or brain. Evidence is also provided that the addition of phloretin during the homogenization process is superfluous, as the use of 80% ethanol and 0.02 M NaOH for this step results in undetectable deiodinase activity. Data are presented showing that during the final sample drying, no losses or degradation of T4 and T3 occur, confirming the adequacy of the individual recovery corrections using radiolabeled iodothyronines as internal tracers. We also present quantitative information on the intralaboratory variability of the T4 and T3 concentrations found in tissues from normal fetuses and their mothers as well as in adult males and nonpregnant females. Results are comparable to those obtained by others using entirely different analytical procedures.

Animals↗
PubMed1994

Thyroid hormone controls the cell-specific expression of the kidney androgen-regulated protein gene in S3 mouse kidney cells.

The kidney androgen-regulated protein (KAP) gene is expressed in epithelial cells of proximal convoluted tubules of mouse kidney. Although TSH proved to be necessary for the constitutive expression of the gene in the outer stripe of the outer medulla, androgens are responsible for expression in cortical segments of the proximal tubules. We have used the congenital thyroid hormone (TH)-deficient hyt/hyt mouse to demonstrate that TH, and not TSH, is responsible for the constitutive expression of the gene in the mouse kidney. Although the androgen-dependent cortical response is partially impaired in hypothyroid mice, the expression can be fully restored after the administration of TH or pharmacological doses of testosterone, suggesting some cooperativity between TH and androgens in promoting cortical KAP gene expression. Results in hyt/hyt mice after treatment with retinoic acid, alone or in combination with TH, demonstrated that this regulator does not have any effect on the regulation of the KAP gene in mouse kidney and that induction of the gene by T3 does not require heterodimerization of TR with retinoic acid-related receptors. By using immunocytochemical analysis and specific antibodies against alpha- and beta-TH receptors we have determined the presence of both types of receptors in all segments of the proximal tubules.

Animals↗
PubMed1994

Protein binding of itraconazole and fluconazole in patients with chronic renal failure.

The serum protein binding of itraconazole and fluconazole, new triazole antifungal agents, has been investigated in vitro in the serum of healthy volunteers and in patients with chronic renal failure (predialysis). Protein binding was determined by ultrafiltration. Concentrations of both alpha 1-acid glycoprotein (AAG) and albumin were measured in all serum samples. The protein binding of itraconazole showed no significant changes in patients with chronic renal failure when compared to healthy volunteers (96.64 +/- 0.99% vs. 96.85 +/- 0.33%). In contrast, fluconazole protein binding was significantly increased in the same patients (22.91 +/- 6.15% vs. 12.51 +/- 2.37%; p < 0.001). In addition, whereas albumin levels in the latter patients were significantly decreased (p < 0.001), their AAG levels were found to be significantly elevated with respect to control subjects (p < 0.001). While no correlation was established between itraconazole protein binding and albumin or AAG concentrations, a significant correlation was found between fluconazole protein binding and AAG levels (r = 0.72; p < 0.001). Fluconazole protein binding was found to be independent of albumin concentrations. In vitro carbamylation of serum protein with potassium cyanate caused no changes in the protein binding of fluconazole or itraconazole. We conclude that the binding of itraconazole by serum proteins is not altered in diseases involving changes of AAG or albumin concentrations. However, fluconazole protein binding may be altered in disease states associated with increased AAG concentrations.

Adult↗
PubMed1993

Effects of iodine deficiency on thyroid hormone metabolism and the brain in fetal rats: the role of the maternal transfer of thyroxin.

Thyroid hormones, thyroxin (T4) and 3,5,3'-triiodothyronine (T3), of maternal origin, are available to the mammalian embryo early in development. However, after the onset of fetal thyroid function, they are of both fetal and maternal origin. Maternal T4 has a protective effect on the fetal brain in cases of congenital hypothyroidism. In severe iodine deficiency, maternal T4 is low, although T3 is normal; the developing embryo is markedly T4-deficient; and T3 deficiency increases with gestational age. In contrast to mechanisms in the hypothyroid fetus from a normal mother, the low T4 of the iodine-deficient mother prevents any protective effects on the fetal brain. Thyroid hormone deficiency of the iodine-deficient fetus, including the brain, is more severe and prolonged than it is in the cases of maternal or fetal thyroid failures. These findings may help to explain the relationship between severe maternal hypothyroxinemia and the severe central nervous system damage of the neurological endemic cretin.

Animals↗
PubMed1993

Differential effects of thyroid hormones on growth and thyrotropic hormones in rat fetuses near term.

We have studied the effects of thyroid hormone deficiency and excess on GH and TSH economy in the rat fetus near term. Pregnant rats were either left untreated (C group) or treated with methimazole to block thyroid function and infused with placebo, T4, T3, or both, until 21 days of gestation. Two experiments were performed: the doses (per 100 g body wt/day) of T4 ranging from 2.4-21.6 micrograms, those of T3 from 1.5-13.5 micrograms, with groups on 2.4 micrograms T4 + 1.5 micrograms T3. Fetal plasma T4 levels varied between 6-160% of C values and T3 values between 52-770%. Both plasma and pituitary GH decreased in hypothyroid fetuses from methimazole dams, and their plasma TSH was elevated. When T4 and/or T3 were infused, plasma and pituitary GH increased as a function of fetal plasma T4 and T3, reaching normal values when plasma T3 levels became normal, then increasing further. The effects on GH economy were related to the plasma T3 level, with no appreciable difference if T3 had been infused or derived from T4. In contrast, the elevated plasma TSH of the hypothyroid fetus decreased toward normal values when fetal plasma levels of T4, and of T3 derived from T4, became normal, but was not affected by normal fetal plasma T3 when T3 was infused. In the absence of T4, T3 decreased plasma TSH only when infused in doses that increased fetal plasma T3 3-fold above C values or more. Thus, both GH and TSH economy are under thyroid hormone control in rat fetuses near term. Similarities and differences with respect to regulation in adult rats cannot, however, be attributed exclusively to differences in fetal somatotrophs and thyrotrophs, because of the possibility that control is exerted at regulatory sites which are unique to the fetus.

Animals↗
PubMed1993

Detection of thyroid hormones in human embryonic cavities during the first trimester of pregnancy.

Transfer of maternal thyroxine (T4) to the human fetus near term has recently been demonstrated. We investigated whether maternal thyroid hormone is available to the conceptus during the first trimester of pregnancy as well. Transvaginal ultrasound-guided puncture of the embryonic cavities was performed during the first trimester of pregnancy to obtain coelomic fluid between 6 and 11 weeks, and amniotic fluid between 8 and 11 weeks of pregnancy. T4 was found in coelomic fluid with mean values (+/- SEM) being 961 +/- 193 pmol T4/L (747 +/- 150 pg/mL). Concentrations increased both with gestational age and with rising maternal serum T4. Concentrations of 3,5,3'-triiodothyronine (T3) were at least 30 times lower, and those of 3,3',5'-triiodothyronine (rT3) four times higher, than coelomic fluid T4. Thyroxine and rT3 in amniotic fluid (8-11 weeks) were markedly lower than in the coelomic fluid, and T3 was undetectable. These results show that maternal thyroxine can cross the placental barrier as early as the second month of pregnancy. T4 from the coelomic fluid may reach the embryo via the yolk sac. This finding raises the possibility that the increase in maternal T4 occurring during the first trimester may be functionally important for the developing embryo, when its thyroid is not yet functioning.

Amniotic Fluid↗
PubMed1993

Propranolol absorption in peptic ulcer disease.

This study was designed to determine whether gastroduodenal ulcer influences propranolol absorption. Eleven patients with peptic ulcer disease and eight healthy subjects received 80 mg of propranolol orally. Serum propranolol levels were measured with high-performance liquid chromatography. Ulcer patients showed a significant decrease in mean peak concentration of propranolol (90 +/- 12 ng/ml versus 151 +/- 23 ng/ml) (p < 0.025), in the absorption constant (1.43 +/- 0.21 h-1 versus 0.96 +/- 0.12 h-1) (p < 0.05), and in the area under concentration-time curve (802 +/- 129 ng/ml.h versus 492 +/- 73 ng/ml.h) (p < 0.05). No significant difference was seen in drug effect on the heart at 90 min. We conclude that propranolol is absorbed more slowly in ulcer patients than in healthy subjects, but this delay has no clinical effect after a single dose.

Adult↗
PubMed1993

Netilmicin kinetics in urology.

Plasma kinetics of netilmicin, an aminoglycoside antibiotic was studied in 62 patients undergoing urologic surgery. Despite the use of a standard 100 mg-dose, no toxic levels were achieved except in one patient. A poor correlation was found between netilmicin plasma elimination constant and creatinine clearance (r = 0.34, p = NS). We can conclude that the prediction of netilmicin plasma concentrations is not possible using only demographic patient's data. The monitoring of netilmicin levels should be performed in long-term treatments but not in 4-dose regimes such as in urologic prophylaxis.

Adult↗
PubMed1993

Unchanged protein binding of penbutolol in renal insufficiency: a possible role of carbamylation.

The effect of in vitro carbamylation of serum protein with potassium cyanate on protein binding of penbutolol, a basic agent exclusively bound to alpha 1 acid glycoprotein (AAG), was investigated. Carbamylation of serum resulted in a weak increase on free fraction of penbutolol (4.45 +/- 0.54% before carbamylation vs 5.66 +/- 0.40% after; p < 0.025). Parallelly, potassium cyanate added to pure AAG and incubated for 90 min induced carbamylation of this protein (38 mumoles of 14C cyanate incorporated per gram of protein). A study in serum from patients with chronic renal disease (pre and postdialysis) showed no changes in protein binding of penbutolol, although AAG levels were significantly higher. However, Scatchard [1949] plot for penbutolol binding to serum from renal patients (both pre and postdialysis) showed a decrease in affinity constant (nKa = 11.13 x 10(5) M-1 in healthy volunteers, vs 5.56 x 10(5) M-1 in patients before dialysis and 4.57 x 10(5) M-1 after dialysis). We concluded that carbamylation of serum AAG in uremic patients could explain, in part, the absence of changes in protein binding of any basic drugs in this pathological condition. It appears that a decreased affinity constant could balance the effect of increased AAG levels.

Adult↗
PubMed1992

Investigation of conformational specificity at GPIIb/IIIa: evaluation of conformationally constrained RGD peptides.

RGD-containing proteins and peptides are known to bind to the platelet GPIIb/IIIa receptor and inhibit platelet aggregation. That a conformational component to the specificity exists is suggested by significantly lower activity of linear RGD analogs relative to closely related cyclic peptides and small proteins containing the RGD sequence. Recently, conformations for a suite of RGD containing cyclic peptides have been defined by NMR-based methods and, for one molecule, by X-ray diffraction. We report here the NMR-based conformational analysis of an additional cyclic peptide, cyclo(Pro-Arg-Gly-Asp-D-Pro-Gly), and compare the conformational variations in the suite of peptides and related analogs. Biological activity data for these peptides shows a preference of the platelet GPIIb/IIIa receptor for one conformation of the RGD sequence, but suggests its ability to bind a second, distinct conformation.

Amino Acid Sequence↗