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Biomedical subjects

R Calvo

Publications and source records attributed to R Calvo.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1992

In vivo potentiation of atracurium neuromuscular blockade by nimodipine in rabbits.

The interaction between nimodipine, a calcium channel blocker, used for the treatment of subarachnoid haemorrhage, and atracurium, was studied in rabbits. An intravenous dose of 0.1 mg.kg-1 of nimodipine given over 3 min caused a potentiation of the neuromuscular blocking action of atracurium (administered at an infusion rate of 7.5 micrograms.kg-1.min-1), measured on the indirectly stimulated tibialis-anterior muscle of the animal. (ED50)inf and (ED95)inf were significantly reduced (30.7% and 23.3%) in nimodipine-treated animals (P less than 0.05 and P less than 0.02, respectively). No changes were observed in recovery rate.

Animals↗
PubMed1992

Influence of changes in protein binding on the central activity of antidepressants.

The central effect (expressed as analgesic response), protein binding and brain uptake of mianserin were measured in mice receiving drug intraperitoneally. A significant decrease of the central effect of mianserin (30 mg kg-1) was seen in mice with experimental inflammation when compared with control animals (reaction time (s) = 12.12 +/- 1.22 vs 25.56 +/- 2.92; P less than 0.001) and the dose-analgesia response curve (10-60 mg kg-1) was significantly shifted to the right in mice with inflammation. In serum of mice with inflammation, unbound concentration of mianserin was decreased from 19.37 +/- 0.73 to 17.83 +/- 0.30% (P less than 0.05) and seromucoid levels were significantly increased (P less than 0.001). Following the intraperitoneal administration of 30 mg kg-1 of mianserin, brain uptake decreased in diseased mice when compared with control animals (P less than 0.02), suggesting that the decrease in analgesia was secondary to a decrease in drug delivery to the brain because of increased protein binding.

Animals↗
PubMed1992

Thyroid hormones and 5'-deiodinase activity in neonatal undernourished rats.

Undernutrition was induced in rats submitted to food restriction from the fetal stage, and malnutrition was continued after birth until 70 days of life. Body weight was decreased to less than 50%. Plasma T4 and T3 and pituitary TSH content were determined between 8-70 days of life. In control rats, plasma T4 and T3 reached a maximum at 14 and 35 days of life, respectively, and TSH pituitary content at 45 days of life. In undernourished rats, after 8 days of life, plasma T4 and T3 and pituitary TSH content were decreased to about 50% or less, and the pattern of sequential changes observed in control rats was absent or modified. T4 and T3 concentrations were measured in heart, liver, and brain in the fetus (22 days old) and 8, 14, and 23 days after birth, as well as liver and brain 5'-deiodinases (5'D). Hepatic 5'D type I was always decreased in undernourished rats from 8-70 days after birth. Liver and heart T4 and T3 concentrations were decreased in 14-day-old undernourished rats as well as brain T3. Brain 5'D type II was decreased at 8 and 14 days, and total brain 5'D activities at 8 days. These changes occurred during the critical period for brain development (7th to 20th day) during which most processes of myelination take place and T3 brain normal levels are required.

Aging↗
PubMed1992

L-thyroxine and 3,5,3'-triiodothyronine concentrations in the chicken egg and in the embryo before and after the onset of thyroid function.

The concentrations of T4 and T3 were measured by specific RIAs in chicken embryonated eggs and embryonic tissues before (at 4 and 6 days of incubation) and after the onset of thyroid function (at 10-20 days). All samples were submitted to extensive delipidation and purification. T4 and T3 were found in the yolk, as described by others, and also in the egg white, although at lower concentrations. The initial total maternal supplies per egg are 67 ng T4 and 30 ng T3 in the yolk, and 2.4 ng T4 and 1.9 ng T3 in the egg albumen. Whole 4-day-old embryos contained a total of 2.48 pg T4 and 0.65 pg T3. The head (mostly brain) of 6-day old embryos contained 4.1 pg T4 and 4.6 pg T3; T4 (but not T3) was also measurable in the carcass. The concentrations of T4 increased progressively between 10 and 20 days in the brain, eyes, liver, and heart; they were especially high in the eyes (4.8 ng/g) and liver (8.2 ng/g) at 20 days. T3 levels increased markedly in the brain (to 5.1 ng/g at 20 days) and less markedly in the eyes (to 1.3 ng/g) and heart (to 1.6 ng/g), but were low and stable in liver up to 18 days (0.3 ng/g), after which there was a sudden increase to 1.4 ng/g at 20 days. Iodothyronines are, therefore, available to the chick embryo throughout development both before and after the onset of thyroid function. T3 concentrations, especially in the brain, reach much higher levels than previously inferred from the low plasma T3 levels. These findings show similarities with those described for the fetal rat.

Analysis of Variance↗
PubMed1992

The rat placenta and the transfer of thyroid hormones from the mother to the fetus. Effects of maternal thyroid status.

We have studied the effects of maternal thyroid status on the effectiveness of the rat placenta near term as a barrier for the transfer of T4 and T3 to the fetus. Dams were given methimazole to minimize the fetal contribution to the T4 and T3 pools, so that the iodothyronines found in the conceptus are ultimately of maternal origin. The dams were infused with saline, or with T4 or T3 at doses ranging from 2.3-27.8 nmol T4 and from 0.77-20.7 nmol T3/100 g BW per day. A group of normal pregnant dams (C) was included. At 21 days of gestation T4, T3, and rT3 were measured by RIA in maternal and fetal plasma, and in maternal and fetal sides of the placenta. The total fetal extrathyroidal T4 and T3 pools were also determined. The dose-related changes in T4, T3, and rT3 levels in the placenta confirm the presence of both inner and outer ring iodothyronine deiodinase activities, and suggest increasing accumulation of the iodothyronines. Despite this, fetal extrathyroidal T4 and T3 increase progressively in T4-infused groups as a function of maternal circulating T4 levels. Fetal extrathyroidal T3 increases progressively in T3-infused groups as a function of maternal plasma T3. There was no evidence that the net maternal contribution of T4 or T3 would be proportionally less when the maternal pools became very high. It was concluded that the rat placenta is only a limited barrier for the transfer of T4 and T3 to the fetus.

Animals↗
PubMed1992

The influence of renal failure on the kinetics of intravenous midazolam: an "in vitro" and "in vivo" study.

The effect of renal failure upon the "in vitro" binding of midazolam, a new water-soluble short-acting benzodiazepine, has been studied in man. An increase of its free fraction (ranging from 2.52 to 5.17%) in serum from uremic patients was observed. A similar situation was originated in rabbits by administering uranyl nitrate (2 mg/Kg i.v.) and posterior hypnosis with midazolam. Uremic rabbits showed a marked increase in the free concentration of midazolam in serum (ranging from 8.9 to 13.7 micrograms/ml) and in midazolam brain levels (156.2 micrograms/g in cortex vs 84.5 micrograms/g in control animals). A positive correlation between brain and serum free concentration of midazolam was also observed. It is concluded that in renal patients more unbound drug is available to produce central nervous system effects, and a decrease in intravenous dose of midazolam could be recommended in this clinical situation.

Adolescent↗
PubMed1992

Homeostasis of brain T3 in rat fetuses and their mothers: effects of thyroid status and iodine deficiency.

Faced with large variations in iodine, T4 or T3 supply, the fetal brain is able to maintain T3 homeostasis to a greater degree than apparent from changes in plasma and other tissues, such as the liver. Changes in the activity of 5'D-II play an important role in this homeostasis, although this does not exclude other regulatory mechanism(s), such as changes in type III (5D) activity, in uptake of the iodothyronines by the brain, or in cerebral iodothyronine turnover rates. T3 generated locally from T4 is more important than plasma derived T3 as determinant of the total T3 available to the brain throughout the life cycle of the rat. It is especially important during the fetal and neonatal phases of brain development, when the brain depends almost exclusively on the supply of T4. Fetal brain T3 homeostasis is maintained despite large fluctuations in the supply of T4. An excess of T3 also affects brain T3 to a lesser degree than it does other tissues. If present results are relevant to man, they suggest that overtreatment of mother of a congenital hypothyroid fetus with T4 is not likely to be harmful for the fetal brain. Treatment with T3 should be avoided, as it deprives the fetal brain of the main regulatory mechanism involved in homeostasis of brain T3, namely generation of T3 from T4.

Animals↗