[Importance of the eosinophil count in respiratory secretions of infants with recurrent obstructive bronchial syndrome].
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Biomedical subjects
Publications and source records attributed to J Mallol.
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Quantitative and qualitative modifications of the specific binding sites for [3H]quinuclidinyl benzylate (QNB), a muscarinic antagonist, were studied during rat cerebellar postnatal development. Specific binding sites for QNB (QNB-sbs), regardless of whether they correspond to muscarinic acetylcholine receptors, are present with the highest density in the archicerebellar cortex, but the total amount per region is about the same in the archi -, paleo-, and neocerebellar cortex regions. Large amounts of QNB-sbs are also present in a cerebellar fraction including central white matter and deep cerebellar nuclei. QNB-sbs are low but present at birth and then accumulate during ontogenic development according to a curve which duplicates, with a delay of a few days, the curve of DNA accumulation. Dissection studies indicated that this curve does not depend on the preferential localization of QNB-sbs in a specific cerebellar region nor on the particular development of this region. The similarity of the QNB-sbs and the DNA developmental curves might indicate that the QNB-sbs are present on granule cells; however, a comparative analysis of the data in the literature suggests that a great many QNB-sbs are located on the Purkinje cell dendrites in the molecular layer, where all or some of them might correspond to the extrajunctional muscarinic acetylcholine receptor detected there by electrophysiology. It would appear that only a small percentage of cerebellar QNB-sbs corresponds to the cholinergic synapses present in cerebellar cortex; hence, the question of muscarinic receptors in the cerebellum should be re-examined.
T4 and T3 have been measured by RIA in 10-12-day-old rat embryo-trophoblasts, and in 13-20-day-old embryos and placentas, as well as in a few samples of amniotic fluid. Both T4 and T3 were measured after extraction of the samples with ethanol, purification by paper chromatography, anion exchange resin, or both. T4 and T3 could be shown in all samples studied. The amounts of T4 and T3 per conceptus and their concentrations were higher in embryo-trophoblasts and placentas than in 13-18-day-old embryos. The concentrations of T4 and T3 remained fairly constant in the embryos until day 19, when they appeared to increase. The molar ratios of T4 to T3 were 1.4, 8.5 and 103 for embryos, placentas and maternal plasma, respectively. These data show that, for at least one mammalian species, embryonic tissues are provided with T4 and T3 from the earliest date studied, namely 4 days after uterine implantation, and well before onset of thyroid function, which in the rat starts after 17 days gestational age. Such a result suggests that statements denying a possible role of thyroid hormones in early embryogenesis ought to be reconsidered.
The 5'-nucleotidase activity of the purified cytoplasmic fraction preparation of bovine brain does not depend on the presence of the divalent metal ions Mg2+, Ca2+, and Cu2+ in the incubation medium. The Zn2+ ion (0.5 mM) causes total enzyme inhibition. Although EDTA and 8-hydroxyquinoline inhibit the 5'-nucleotidase from this source, it has not been possible to show the existence of metal ions in the enzyme molecule. The inhibition of 5'nucleotidase by EDTA is progressive and irreversible; when the enzyme is not preincubated with EDTA, the inhibition is overridden by metal ions. The purines (except xanthine, 0.3 mM), pyrimidines, and their nucleosides do not affect the 5'-nucleotidase activity. The nucleoside di- and triphosphates are competitive enzyme inhibitors against 5'-AMP as substrate. The Ki values of the diphosphates are lower than those determined for the corresponding triphosphates. The inhibition caused by the above nucleotides is reversed, partly or wholly, by Mg2+, depending on the molar ratio between the effectors. The inhibitory action of the -SH group reagents on the 5'-nucleotidase activity is weak and reversible.
Previous results are contradictory regarding the concentration of thyroxin in human milk. Using a sensitive radioimmunoassay, we have found a lack of parallelism between the standard curve for thyroxin and the curve for serial dilutions of whole human milk, skimmed milk, or ethanol extracts of milk. Nonspecific binding also indicated the presence of analytical artifacts. Thus we have separated thyroxin from other milk components by means of a strongly basic Bio-Rad anion-exchange resin with quaternary ammonium exchange groups attached to a styrene divinyl benzene copolymer lattice, radioimmunoassaying the fractions eluted with an equivolume mixture of acetic acid and water. Parallelism with the standard curve was good, and results were the same whether or not the resin eluate was further purified by paper chromatography. The range of thyroxin concentration in 21 samples of human milk was 0.29-2.00 micrograms/L (mean 0.71, SD 0.40, microgram/L). Such concentrations are unlikely to afford protection to the developing brain of a breast-fed athyreotic baby, as previously claimed.
The membrane-bound acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7) from adult rat brain has been purified to homogeneity using sequential affinity chromatography on Con A-Sepharose and on dimethyl-aminoethylbenzoic acid-Sepharose 4B followed by DEAE-cellulose chromatography. The yield of the purified enzyme (specific activity: 3068 U/mg protein) is higher than 50%. Polyacrylamide gel electrophoresis in the presence of Triton X-100 gives only one band with acetylcholinesterase activity. With the exception of electrofocusing and pore gradient electrophoresis, where a multiple band pattern was detected (which seems to be artefactual), the enzyme appears to be homogeneous. Gel filtration and sucrose density gradient centrifugation in the presence of Triton X-100 give only one symmetrical peak, with a calculated molecular weight of 328 000. Since polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS) and mercaptoethanol gives only one band with a molecular weight of 74 500, a tetrameric structure can be postulated for the membrane-bound acetylcholinesterase from rat brain.
Female rats were killed 15 days, 2 months, and 4 months after surgical thyroidectomy that was followed by injection of 100 microCi 131I. The concentrations of T3 and T4 were measured in tissues (liver, kidney, brain, heart, and hindleg muscle) specific RIAs. Results were compared to those found in intact rats. Thyroidectomy resulted in severe hypothyroidism by 2 and 4 months after the operation, as assessed by undetectable levels of T4 and T3 in unextracted plasma, high circulating TSH, hypothermia, stasis of body weight increase, and depletion of pituitary GH content. Concentrations of T4 and T3 in plasma, as determined after extraction and concentration, were very low, being less than 5% of the normal value by the earliest observation period (15 days). In contrast, although tissue concentrations and total organ contents also decreased after thyroidectomy, they were still clearly detectable 4 months after thyroidectomy. The rates of decrease of T4 and T3 concentrations in most tissues were markedly slower than expected from their rapid decrease in plasma. Some tissues still contained 20% of the normal level 2-4 months after ablation of the thyroid. Tissue levels of thyroid hormones were hardly detectable in rats thyroidectomized 6 months before, having decreased in most tissues to less than 5% of the normal value. Several animals from this group had died. It is concluded that tissues from severely hypothyroid thyroidectomized rats may contain higher concentrations of T4 and T3 than previously thought. The idea that thyroid hormone is not essential for life, based on the assumption that thyroidectomized animals survive without thyroid hormones, might have to be reevaluated.
All the boys and girls between six and fourteen years old regularly attending school in three villages from an area in Spain known ass Las Hurdes were studied with respect to thyroid size, body weight and height. Casual urine samples were obtained for the determination of iodine and creatine concentrations. Capillary blood was spotted on filter paper and used for the determination of thyroxine and thyrotropin by radioimmunoassay. The same survey was carried out in 354 school children from Madrid, whose data were used as a reference of the adequacy of the methods employed in Las Hurdes. Goitre prevalence was very high, the overall frequency being 86 per cent. The concentration of iodine in the urine was less than 20 micrograms/1 in 71 per cent of the school children. The concentration of creatine in the urine was also half that found in children from Madrid, and the daily creatine excretion in children from Las Hurdes was lower than expected from their body weight. Their somatic development, as measured by height and weight, was retarded markedly, both as compared to the Madrid reference group and to international charts. Serum T4 was less than 78 nmol/l ( micrograms/kl) in 46 per cent, of the children from Hurdes, and serum TSH greater than 7.5 mU/l in 40 per cent. A relatively low stature (below the 10th percentile) was associated with either a low serum T4, an elevated serum TSH, or both, in 30 per cent of the children. These results indicate that the persistence of endemic goitre in Las Hurdes is of great significance and that there is a continuing risk of the birth of cretins. Observations made a decade earlier in the same area show that the goitre endemic is not diminishing, and that an iodization programme is urgently needed. It also appears that a high proportion of the "normal' schoolchildren have features found in hypothyroidism.
To determine whether T4 has an intrinsic effect at the pituitary level, it would be important to block conversion of T4 to T3 completely. We have attempted to achieve this with iopanoic acid (IOP), a radiographic contrast agent. We have then measured in the same animals the effects of such treatment on the conversion of T4 to T3 or on the deiodination of T3 and on the pituitary response to a dose of T4 or T3. Plasma TSH levels and pituitary GH content were measured as biological end points. Thyroidectomized rats were injected with a single dose of T4 (1.7 micrograms/100 g BW) labeled with [125I]T4 (Exp A) or with a single dose of T3 (0.33 microgram/100 g BW) labeled with [125I]T3 (Exp B) and treated with IOP or solvent. Animals of Exp A were killed 24 h after iodothyronine injection and those of Exp B were killed 4, 12, and 24 h after injection of the iodothyronine. The concentrations of [125I]T4 and [125I]T3 were measured in several tissues, including the anterior pituitary, after extraction and paper chromatography and quantified with the aid of 131I-labeled markers added in vitro. Plasma and pituitary T3 and T4 plasma TSH, and pituitary GH were measured by specific RIAs. Results show that treatment with IOP markedly inhibits the conversion of T4 to T3 and the deiodination of T3. In IOP-treated thyroidectomized rats, the injection of T4 results in little, if any, effect at the pituitary level, despite an almost 3-fold increase in the percentage of injected T4 found in the gland. Treatment with IOP does not inhibit the effects of a T3 dose; if anything, they appear to be enhanced. It is concluded that, as assessed from biological responses involving the anterior pituitary, a dose of T4 has little if any effect other than that which can be attributed to the T3 generated from it.
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The main objective of this study was to evaluate the effect of fenoterol alone or associated with ipratropium bromide or steroid on the heart rate in young children. Ninety-four infants less than 1 year of age were randomly allocated to receive nebulized fenoterol alone, fenoterol plus ipratropium bromide, fenoterol plus corticosteroids, or normal saline solution. An increase in heart rate was observed in all four groups. The increases were statistically significant (P less than 0.001) in all three treatment groups, and no difference between them was observed (F = 0.65, NS). However, the heart rate remained within clinically acceptance limits. We conclude that nebulized fenoterol alone or combined with ipratropium or steroids can be safely used in the treatment of wheezy infants.
The main purpose of this study was to evaluate four different forms of treatment in young infants admitted for acute wheezing (AW). Seventy-nine infants less than one year of age were randomly assigned to one of five groups. Group 1 received nebulized fenoterol plus ipratropium bromide, group 2 fenoterol, group 3 fenoterol plus steroids, and group 4 aminophylline, IV, plus steroids and oral fenoterol; the control group, or group 5, received nebulized normal saline solution. Clinical evaluation was done by means of a scoring system. The effectiveness of treatments was estimated by a score decrease in the first 24 hours, by the percentage of patients whose scores did not decrease during the same period, and by the number of days in the hospital. All infants had significantly decreased scores, except those in the control group; the aminophylline group included a greater percentage of patients who did not abate their scores, and they stayed in the hospital for more days than those in the other groups. The fenoterol group had the shortest hospital stay. All four treatments produced objective clinical improvement in bronchial obstruction. However, the nebulized bronchodilator treatments were more effective than aminophylline IV in decreasing scores on the first day, and they resulted in shorter hospitalization.
Twenty-eight infants admitted to Exequiel González Cortes Children's Hospital because of acute wheezing (AW) were randomly assigned to three study groups. Fenoterol (FNT), ipratropium bromide (IB), and placebo were administered respectively to children in the different groups by means of metered dose inhalers (MDI) with spacers, using doses of 3 puffs every hour, for 4 hours. The degree of bronchial obstruction was assessed clinically and scored with the single-blind method every hour prior to each treatment. The criterion of a bronchodilator effect was a significant decrease in the degree of bronchial obstruction at subsequent scorings. The scores of the three groups were compared using the Student's t test for matched samples. The same test was also applied to the independent samples for determining the superiority of one treatment, FNT or IB, over the other. The results indicated a significant decrease in the scores of the groups receiving FNT and IB (P less than 0.05); this did not occur in the group in which placebo was used. FNT produced a more rapid and sustained effect than IB (P less than 0.05). Significant bronchodilator effect was obtained in infants with AW when repeated doses of FNT or IB were administered with MDI and spacers. This effect was significantly greater in the group treated with FNT.
Reserpine (0.5 mg/kg i.m.) produced emesis in pigeons with 60% of the animals responding. Metoclopramide HCl at 10, 20 and 40 mg/kg p.o. administered 30 min before or after reserpine injection was effective in blocking reserpine emesis. Metoclopramide was unable to antagonize reserpine-induced sedation and hypotension in rats, thus inviting discussion of its possible mechanism in blocking reserpine emesis.
Administration of Benzo(a)pyrene (BP, 50 mg/kg/d) to pregnant rats significantly increased Glutathione S-transferase (GST) activity in placental tissue-extract (Vmax = 40 nmol/min/mg protein and 69 nmol/min/mg protein in controls versus treated animals respectively; P less than 0.01) and total fetal tissue-extract (Vmax = 51 nmol/min/mg protein and 82 nmol/min/mg protein in controls versus treated animals respectively; P less than 0.01) indicating an induction effect of BP on the GST system. An increase in the Km values was also observed: 1.61 x 10(-3) M and 2.84 x 10(-3) M in control versus treated placentae; 1.38 x 10(-3) M and 2.05 x 10(-3) M in control versus treated fetuses. A competitive effect on the enzyme by the BP present in the sample may also be involved. The glutathione content in both tissues did not show any changes after the treatment with BP. This increase in the GST system was not sufficient to protect the fetus. BP affected the reproductive performance of pregnant rats by significantly increasing the number of resorptions and fetal wastage, and, also, by decreasing the fetal weight.