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Biomedical subjects

A Hernandez

Publications and source records attributed to A Hernandez.

At least 145 records · Page 8Linked to original sources

Lack of interspecies barriers in anti-Id stimulated antibody production against Echinococcus granulosus antigens.

Polyclonal human anti-hydatid antibodies were affinity purified from a hydatid patient serum and used to produce a rabbit anti-idiotypic serum. These anti-Id antibodies cross-reacted in ELISA with sera from 11 of 12 hydatid patients studied and with 13 infected or immunized mice sera. All mice primed and boosted with anti-Id produced anti-hydatid antibodies in the primary response and exhibited an increase in antibody titre after a booster injection. The same effect was observed with mice primed with antigen and boosted with anti-Id, although these mice exhibited higher antibody titres. A significant idiotype repertoire is shared by anti-hydatid antibodies produced by different individuals of the same or different species, and anti-Id raised against those antibodies behave as surrogate antigens producing a normal primary and secondary response in animals of different species from that used to isolate the Id.

Animals↗

Thyroid hormones and 5'-deiodinase in rat brown adipose tissue during fetal life.

Brown adipose tissue (BAT) iodothyronine 5'-deiodinase (5'D) activities are very high during fetal life but decrease 10-fold a few hours before birth. Accordingly, BAT 3,5,3'-triiodothyronine (T3) concentrations are also very high. The temporal patterns of changes in BAT 5'-D and fetal plasma insulin are similar (and differ from the pattern for catecholamines) but are not superimposable. A causal role for insulin in the activation of fetal BAT 5'-D is therefore not supported by the data. Maternal thyroidectomy leads to a decrease in the total and relative weight of fetal BAT and to a 30-50% increase in BAT 5'-D activities; BAT thyroid hormone concentrations are essentially unchanged. Fetal hypothyroidism was induced by giving methimazole and resulted in a marked decrease of BAT thyroxine (T4) and T3 concentrations. This treatment increased BAT 5'-D activity only on day 21 of gestation, but no effect was observed on day 20. The fetal 5'-D response to thyroid hormones infused into the methimazole-treated dams was studied at 21 days of gestation. The increase in BAT 5'-D induced by methimazole treatment was prevented by T4 infused into control dams but not by T3. In fetuses from thyroidectomized dams, the pattern of 5'-D regulation by thyroid hormones was impaired. It is suggested that the high concentrations of thyroid hormones present in fetal BAT might participate in the general maturation and development of fetal BAT.

Adipose Tissue, Brown↗

Effect of clonidine early in life on brain morphofunctional deficits induced by neonatal malnutrition in the rat.

A great body of evidence indicates that malnutrition early in life induces central noradrenergic hyperactivity (CNH). On the other hand, it is known that noradrenaline (NA) is an important regulator of the regressive processes occurring during synaptogenesis such as cell death, axonal pruning and synaptic elimination. This leads to the hypothesis that some of the morphofunctional modifications induced by malnutrition on the brain could be due, at least in part, to an increase of NA activity during the period of accelerated brain growth. This study evaluates whether early reduction of CNH by the alpha-2 presynaptic adrenoreceptor agonist clonidine, prevents long-term morphofunctional deficits induced by protein-energy malnutrition in the rat. Results of experiments performed on 45 day-old malnourished animals that received clonidine during the suckling period, show that the pharmacological treatment prevented: (i) deficits in both NA levels and NA release in the visual cortex; (ii) deficit in brain weight but not in body weight; and (iii) reduction of the normal brain interhemispheric asymmetry of visual cortical evoked potentials. It is suggested that administration of clonidine early in life prevents brain morphofunctional deficits by malnutrition, by restoring the normal tropic role of NA during synaptogenesis.

Animals↗

Role of the mediators in pulmonary hyperreactivity: the cocktail interaction hypothesis.

Pulmonary hyperreactivity is a common feature in asthma. In the present study we investigated the possible role of different mediators in the genesis of this phenomenon. In particular the ability of prostaglandin D2 (PGD2), substance P (SP) and bradykinin (BK) to potentiate acetylcholine (ACh)-induced bronchospasm was assessed in anaesthetized and mechanically ventilated guinea-pigs. Threshold doses of PGD2, SP and BK significantly enhanced ACh-induced bronchospasm in normal guinea-pigs, even if a different trend in the onset and duration of the phenomenon was observed. Ovalbumin (OA) active sensitization modified the ability of the three compounds tested to positively interact with ACh. Beta-adrenoceptor blockade due to propranolol treatment increased the positive interaction between the three compounds and ACh. The role of PGD2, SP and BK in the genesis of pulmonary hyperreactivity is proposed and the relevance of mediator-mediator interaction during adrenergic imbalance is discussed.

Acetylcholine↗

Beta-adrenoceptor desensitization in a model of experimental asthma in guinea-pigs.

We investigated the possible occurrence of the desensitization of pulmonary beta-receptors in a model of experimental asthma such as the ovalbumin sensitized guinea-pig. Although some differences were observed between normal and asthmatic guinea-pigs, the desensitization procedure (isoproterenol (ISO) 10(-6) M x 20 min x 2) markedly impaired the relaxing capacity of ISO, epinephrine (EPI) and procaterol. With the beta 2 agonist procaterol, the sensitized tissues seemed to be more sensitive compared to normal. In parallel, the desensitization procedure produced a greater decrease in the relaxing capacity of procaterol in the sensitized tracheas. On the other hand, the two unselective beta-agonists (ISO and EPI) did not seem to discriminate between the two experimental conditions used. These data suggest that the immunological disturbance due to the active sensitization may induce a modification in beta-adrenoceptor reactivity. The results obtained with EPI after anaphylactic challenge are in agreement with this. In fact, the relaxing capacity of EPI was markedly reduced by antigen challenge.

Adrenergic beta-Agonists↗

Lapidus: when and why?

The Lapidus procedure for correction of hallux valgus has fallen into disfavor over the years because of its complexity and often poor results. This article re-examines the Lapidus and describes its indications and use. The authors contend that the procedure does have efficacy and a place in the foot surgeon's armamentarium.

Arthrodesis↗

Intracytoplasmic triglyceride accumulation produced by dexamethasone in adult rat hepatocytes cultivated on 3T3 cells.

Glucocorticoids, such as hydrocortisone (HC) and dexamethasone (DEX), when administered to rats, induce lipid accumulation within hepatocytes (fatty liver). To investigate whether glucocorticoids can produce triglyceride (TG) accumulation as they do in vivo and the involved mechanisms, we have used primary cultures of rat hepatocytes which synthesized and secrete triglycerides into the culture medium. Hepatocytes cultivated on a feeder layer of lethally treated 3T3 cells were exposed for 2 weeks to micromolar concentrations of DEX. This glucocorticoid caused morphological alterations and cells accumulated lipid droplets in their cytoplasm; the TG content increased up to 6-fold in a concentration- and time-dependent manner. The removal of [14C]acetic or [14C]oleic acid from the culture medium was not altered in the cultures treated with 50 micrograms/ml DEX but the incorporation of [14C]acetic and [14C]oleic acid into TG in these cultures was about 13-fold and 60% higher than in non-treated cells, respectively. On the other hand, hepatocytes treated with 50 micrograms/ml DEX for 2 weeks showed a 16-fold decrease in TG release and 40% inhibition in protein export, whereas synthesis of total cellular proteins was not altered. Our results show that corticosteroids, such as DEX, caused lipid accumulation in liver cells through an increased synthesis and/or esterification of fatty acids, but mostly through a decrease in the secretion of TG.

Animals↗

Topical application of morphine to the rat somatosensory cortex produces analgesia to tonic pain.

Topical application of 0.01 or 0.1% morphine solution to the somatosensory SI area of the rat cerebral cortex significantly decreased the pain intensity rating in the formalin test without producing motor side effects or sensory deficits. Naloxone partially antagonizes this effect. Topical application of morphine to the striate cortex did not induce analgesia. It is suggested that the primary somatosensory SI area of the cerebral cortex plays a role in opiate pain control.

Animals↗

Dilated cardiomyopathy in infants and children.

The outcome of medical treatment of dilated cardiomyopathy in infants and children was reviewed to develop a predictive index for selection of patients likely to benefit from cardiac transplantation. The clinical findings, laboratory investigations, treatment and outcome of 20 patients (Group 1) less than 2 years of age at presentation and 12 patients (Group 2) greater than 2 years of age at onset were compared. Of 20 Group 1 patients, 5 (25%) died. Available autopsies (four patients) showed endocardial fibroelastosis. Of 15 survivors, 10 showed improvement in cardiac status and 5 remained unchanged. Ninety-three percent of survivors had dilated cardiomyopathy consistent with endocardial fibroelastosis by angiocardiography. All 12 Group 2 patients died. In addition to age at presentation and poor outcome, Group 2 differed from Group 1 in having a higher incidence of other family members with cardiomyopathy, more significant rhythm disturbances at presentation and a more rapid course to death. Risk factors of poor outcome in both groups included persistent cardiomegaly and the development of significant arrhythmias by Holter electrocardiographic monitoring. Cardiac transplantation is recommended for children with dilated cardiomyopathy presenting after age 2 years who survive 1 month. Those patients less than 2 years old at presentation whose condition has not improved after 1 year and who have persistent cardiomegaly or complex ventricular arrhythmias may also benefit from transplantation.

Actuarial Analysis↗

Croton oil pleurisy induces pulmonary hyperreactivity.

Inflammatory process of the airways has been claimed to be relevant to the development of bronchial hyperreactivity in different experimental models. We investigated the consequences of pleural inflammation induced in the guinea-pigs by croton oil injection into the pleural space. Croton oil injection was followed by the development of an inflammatory reaction localized to the pleura as shown by recovery of inflammatory exudate from the pleural cavity of treated animals. An increased number of white cells was observed in the pleural fluid of treated animals as compared to control. Moreover, the croton oil induced inflammation was characterized by development of pulmonary hyperreactivity which involved both airway and vascular smooth muscles. We also studied this phenomenon in an animal model of asthma, such as the actively sensitized guinea-pigs. Polymorphonuclear leukocyte and particularly eosinophil recruitment was increased in this experimental condition and a different trend in the development of the hyperreactive phenomenon was observed. Our data support the relationship between inflammatory process within the pleural space and increased reactivity of pulmonary tissues. The possible involvement of different classes of white cells in this phenomenon has also been discussed.

Animals↗

Successful vaccination against murine Schistosoma mansoni infection with a purified 12 Kd Fasciola hepatica cross-reactive antigen.

A 12 Kd antigen was isolated from Fasciola hepatica adult worm extracts by gel filtration in Sephadex G-50 and ion exchange chromatography using DEAE Sephadex A-120. Mice immunized with this Fasciola-derived 12 Kd antigen developed antibodies to Schistosoma mansoni adult worm extracts, demonstrating its cross-reactivity with schistosomes. Vaccination of mice with microgram amounts of the antigen in Freund's adjuvant induced up to 77% reduction in worm burdens after challenge with S. mansoni cercariae. F. hepatica 12 Kd degraded by proteinase K to lower molecular weight polypeptides which still retain their antigenicity as determined by the enzyme-linked immunoelectrotransfer blot technique. Treatment with either Endoglycosidase H, neuraminidase, or dithiothreitol had no effect on its mobility in sodium dodecyl sulfate polyacrylamide gels, or in its recognition by antibody, suggesting the absence of carbohydrate moieties or disulphide bonds in relation to its antigenic determinants and also suggesting that the antigen is a pure polypeptide. These studies establish that a molecularly defined cross-reactive component of one parasitic trematode (F. hepatica) induces resistance to challenge infection with another parasitic trematode (S. mansoni). Its polypeptide nature makes recombinant DNA technology an alternative for the manufacture of a vaccine.

Animals↗

The effect of tunicamycin on Leishmania brasiliensis. Glycosylation and the cell surface components.

Culture conditions of Leishmania cells were developed to allow the study of the effect of tunicamycin (TM) on glycosylation and on the cell surface components. Leishmania incorporate [14C]-mannose and [35S]-methionine in vitro. The incorporation of [14C]-mannose is linear for 150 min and is inhibited by TM (2 micrograms/ml) in a time dependent effect which reaches a plateau of 45% inhibition at 36 h. Under the same experimental conditions [35S]-methionine incorporation into protein is slightly affected. This is reflected by an almost identical polypeptide pattern for TM treated and non-treated cells when analyzed on SDS-PAGE. On the contrary, strong differences were detected on the labeled compounds analyzed on SDS-PAGE followed by autoradiography when the precursor used was [14C]-mannose. A shift in the electrophoretic mobility of most of the glycopeptides synthesized in the presence of TM was observed, which is also reflected in the structure of the main Leishmania cell surface components. The findings are discussed in the light of biological implications.

Animals↗

Norethisterone contraceptive microspheres.

Two formulations of polylactic and polyglycolic acid microcapsules containing 75 and 100 mg of NET respectively were studied for a 90-day period of anticipated contraceptive effect in two groups of five women. A 200 mg dose of NET preparation was also studied for a 180-day period of anticipated contraceptive effect in 19 women. Alteration in menstrual cycle, with tendency to short bleeding episodes, spotting days, and amenorrhea were the most important collateral effects. In the majority of cases, ovulation was inhibited. No cases of pregnancy were presented. The obtained NET circulating levels were very stable during the period of anticipated contraceptive effect.

Contraception↗

Locus coeruleus stimulation modulates olfactory bulb evoked potentials.

Field-evoked potentials from the main olfactory bulb in response to stimulation of the olfactory nerve and lateral olfactory tract were measured without and with conditioning stimulation of the locus coeruleus noradrenergic system. The locus coeruleus conditioning stimulus suppressed or inhibited the late components of the olfactory bulb potential evoked by orthodromic olfactory nerve stimulation; this inhibitory effect was suppressed by the microinjection of the alpha-adrenergic blocker prazosin into the olfactory bulb. Results indicate that noradrenergic fibers projecting from the locus coeruleus exert modulatory influences on neuronal networks underlying orthodromic evoked responses in the main olfactory bulb.

Adrenergic Fibers↗

PGD2 induces pulmonary hyperresponsiveness to acetylcholine in vivo in the guinea-pig.

1 A threshold dose of Prostaglandin D2 (PGD2) (0.5 microgram/kg i.v.), which did not modify the basal values of airway resistance, potentiated the acetylcholine induced bronchospasm in anaesthetized guinea-pigs. 2 beta-adrenoreceptors blockade induced by propranolol enhanced the positive interaction between PGD2 and acetylcholine in the pulmonary dynamics. 3 Active sensitization of guinea-pigs by ovalbumin increased the pulmonary PGD2-acetylcholine interaction and the phenomenon was sustained during the time. 4 The inability of PGD2 to potentiate histamine-induced bronchoconstriction suggests a specificity for the interaction.

Acetylcholine↗

Hormone regulation of the rodent Harderian gland: binding properties of the androgen receptor in the male golden hamster.

Studies were conducted in castrated golden hamsters to assess whether sexual dimorphism and sensitivity to sex steroid hormones in the rodent Harderian gland are mediated by an interaction of androgens with specific intracellular receptors. Physical properties, binding kinetics and stereospecificity of the androgen receptor were analysed using [3H]mibolerone as the radioligand. The presence of [3H]mibolerone-androgen receptor complexes with a sedimentation coefficient of 7-8S was demonstrated in Harderian gland cytosol by a linear sucrose gradient ultracentrifugation technique using a vertical rotor. Kinetic analysis revealed an androgen-binding site with an apparent dissociation constant of 0.3 +/- 0.07 (S.D.) nmol/l and a saturation binding capacity of 113 +/- 15 fmol/mg protein. Displacement studies indicated that unlabelled mibolerone, methyltrienolone, 5 alpha-dihydrotestosterone and testosterone were efficient competitors for the androgen-binding sites, while progesterone, 17 beta-oestradiol, dexamethasone, dehydroepiandrosterone, ethiocholanolone and 5 alpha-16-androsten-3-one were not. Experiments in longterm castrated animals revealed that the Harderian gland androgen receptor concentration and sedimentation coefficient remained unmodified. The results of these studies were interpreted as demonstrating the presence of a specific high-affinity intracellular androgen receptor in the male hamster Harderian gland.

Animals↗

Early malnutrition and changes in the induced release of noradrenaline in the prefrontal cortex of adult rats.

The influence of early protein-energy malnutrition on the induced release of noradrenaline in the rat prefrontal cortex was studied: (i) by evaluating in vivo the release of the neurotransmitter as revealed by changes in the ability of pyramidal cells to integrate transient transmembrane currents generated by discrete packets of noradrenaline released by repetitive electrical stimulation of the locus coeruleus; and (ii) by measuring in vitro the potassium-induced release of 3H-noradrenaline in slices obtained from the brain frontal pole. Both electrophysiological and neurochemical data show that, in malnourished rats, weak stimulation produces an increased release, whereas strong stimulation results in a decreased release of the neurotransmitter. The results provide direct evidence that malnutrition alters the release of noradrenaline at the cortical level. Since the prefrontal cortex is involved in cognitive processing, the present results could provide functional evidence linking nutritional and behavioral deficits.

Age Factors↗