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J F Horga

Publications and source records attributed to J F Horga.

25 records · Page 2Linked to original sources
PubMed1980

On the release of catecholamines and dopamine-beta-hydroxylase evoked by ouabain in the perfused cat adrenal gland.

1 Secretion of catecholamines (CA) and dopamine-beta-hydroxylase (DBH) activity from the retrogradely perfused cat adrenal gland was studied following ouabain infusion. Perfusion with ouabain (10(-4) M) for 10 min caused a gradual release of CA in the effluent which reached its peak 30 min after the ouabain pulse, and was maintained constant for at least 1 h. The effect of ouabain seemed to be irreversible. 2 Mecamylamine, while blocking the CA secretory effects of acetylcholine (ACh) perfusion, did not affect the secretion of CA evoked by ouabain. In denervated adrenal glands, ouabain-induced CA secretion was similar to that in the contralateral, innervated gland. However, physostigmine perfusion potentiated the CA secretory effects of ouabain. 3 The release of CA evoked by ouabain was accompanied by a proportional release of DBH activity. The time course of appearance of DBH activity followed the pattern of CA release. 4 The CA and DBH outputs in response to a pulse of ouabain were suppressed in the absence of calcium. Calcium reintroduction to a calcium-free perfused, ouabain-treated gland not only restored but greatly potentiated the release of CA and DBH. The amplitude of the secretory response to calcium reintroduction in ouabain-treated glands was proportional to the extracellular calcium concentration, and was antagonized by an external sodium-deficient medium. 5 These data demonstrate that ouabain releases CA from the perfused cat adrenal gland by a calcium-dependent exocytotic mechanism. The secretory effect of ouabain is not secondary to the release of ACh from cholinergic nerve terminals present in the adrenal gland, but due to a direct action on the chromaffin cell itself. In addition, the results suggest that this action is exerted through redistribution of monovalent cations secondary to the inhibition by the glycoside of the sodium pump. Such monovalent cation redistribution may cause a rise of intracellular ionized calcium levels through the activation of an internal sodium-dependent calcium influx system probably located in the chromaffin cell membrane.

Adrenal Glands↗
PubMed1978

Tissue and plasma catecholamines and dopamine beta-hydroxylase activity of various animal species after neurogenic sympathetic stimulation.

1. The effects of reserpine and exposure to a stressing atmosphere containing 20% CO2 for 5 hr on catecholamine (CA) levels and dopamine beta-hydroxylase (DBH) activity of adrenal, spleen and plasma of cat, rabbit, rat and guinea-pig were studied. 2. Twenty-four hr after an I.P. injection of reserpine, the CA contents of the adrenals and spleens were markedly reduced in all the four species studied. Adrenal and splenic DBH activity was unchanged in reserpine treated cats and rats. The enzyme activity decreased by 28 and 36% in adrenals of rabbits and guinea-pigs, and a 33% diminution was observed in the spleens of both species. 3. A marked rise in guinea-pig plasma DBH activity was obtained 24 hr after reserpine, while plasma DBH activity was unchanged in the rat. 4. Exposure of rats to a stressing atmosphere containing 20% CO2 for 5 hr increased the circulating noradrenaline (NA) levels by 600%, but plasma DBH activity remained unchanged. CO2 exposure caused both, an increase in plasm NA levels and DBH activity in the guinea-pig (950% and 100%, respectively). 5. The combined treatment with reserpine plus immediate exposure to CO2 produced a 230% rise in rat plasma NA with no concomitant change in DBH activity. A similar treatment caused a 75% fall of NA levels and an increase in DBH activity of 600% in the guinea-pig. 6. The ratios of total DBH activity to CA in the spleen and adrenal were much higher in the guinea-pig than in the rat. The fraction of the total DBH activity that can be solubilized by osmotic shock of purified adrenomedullary chromaffin granules was 28% in the rat and 71% in the guinea-pig. If one makes the assumption that 'soluble' and 'releasable' DBH may be equated, the amount of 'releasable' DBH into the circulation is much greater in the guinea-pig than in the rat. 7. The results suggest that the guinea-pig is a better model than the rat to study circulating DBH activity as an index of exocytotic CA release from adrenergic neurones and adrenal medulla, and therefore of sympathetic activity. The results also indicate that previous data trying to correlate sympathetic activity with circulating DBH activity carried out in the rat have to be reconsidered in the light of data obtained in the guinea-pig.

Adrenal Glands↗
PubMed1977

Release of noradrenaline by the ionophore X537A from normal and reserpinized guinea-pig atrium.

The effects of ionophore X537A on the release of 3H-noradrenaline and its metabolites from the superfused guinea-pig left atrium were investigated. Concentrations of ionophore of 10 and 30 mocrometer greatly increased the release of tritium. Of the total increase in radioactivity elicited by X537A 44% was accounted for as noradrenaline and 50% was due to deaminated metabolites. The ionophore-evoked release of tritium was independent of the extracellular calcium ions and was not affected by agents which modify calcium movements such as verapamil, ryanodine, ruthenium red and tetracaine. X537A released 3H-noradrenaline from extragranular sites in MAO-inhibited atria from reserpine-treated animals and this release was also calcium independent. It is concluded that the ability of X537A to release noradrenaline from vesicular or cytoplasmic sites is not related to its ability to couple with and transport calcium ions through membranes. The ionophore might modify the ionic distribution outside and inside the neuronal membrane which would lead to leakage of the transmitter.

Animals↗
PubMedDate not supplied

[Bioequivalence and generic drugs. I. Studies of bioequivalence, considering the theoretical basis, design and use].

OBJECTIVES: To describe the studies done before a generic drug is marketed. DEVELOPMENT: We reflect on the concept of bioequivalence and its limitations, then describe the parameters on which a study of bioequivalence is based and explain the statistical hypothesis of bioequivalence. Finally, we explain the process of a clinical trial of bioequivalence and how the results are analyzed, using a clinical trial as an example. We show how 'carry-over', formulation and period effects are analyzed; and also how bioequivalence may be evaluated by using different approximations: construction of the confidence interval, confidence hypothesis and nonparametric approximations. Finally, we mention the methods used to estimate the size of the sample required in a study of this kind. CONCLUSIONS: Studies of bioequivalence, even the simplest, have peculiarities of design and statistical basis which are markedly different from other clinical trials. When generic drugs are marketed it is important to know about the peculiarities and characteristics of the studies on which affirmation of the bioequivalence of these products is based.

Clinical Trials as Topic↗
PubMedDate not supplied

[Bio-equivalence and generic drugs. Studies of bio-equivalence. II. Special situations. Reflections on problems which may arise with drugs habitually used in neurology].

OBJECTIVE: To discuss some controversial aspects and special situations which should be considered when assessing the use of generic drugs, especially those frequently used in neurology. DEVELOPMENT: We discuss the difference between the concept of average bio-equivalence and individual bio-equivalence, and the implications the selection of one or other criterion may have in the treatment of individual patients with carbamazepine. We also discuss the peculiarities and problems concerning bio-equivalence in the case of drugs with non-linear pharmacokinetics, controlled-release formulations, racemic drugs with two or more stereo-isomers and when there are differences in the excipients of different formulations of the same drug. CONCLUSIONS: There are drugs in which it may be very difficult to show the bio-equivalence of a generic formulation because of its pharmacokinetic characteristics as occurs in the case of controlled-release drugs, the presence of active metabolites or differences in their enantiomers or even due to problems with the excipients used, although if the therapeutic range is wide and these variables are controlled in the studies done, the conclusions regarding bio-equivalence may be valid.

Calcium Channel Blockers↗
PubMedDate not supplied

[Drug-induced extrapyramidal disorders].

We analyze 402 drug-adverse events consisting of movement disorders or aggravation of parkinsonisms, submitted to Sistema Español de Farmacovigilancia until 1994. Our aim is to know patient characteristics and the drugs related with these submissions. Most of them (64) belong to calcium-entry blocker group (31%) and benzamides (27%). Case age intervals more frequent were 11-30 and 60-80 years-old and the events affect predominantly females. The percentage of serious adverse events were near 80%. We think that drug-related parkinsonisms have high prevalence rate and that the role of calcium-entry blockers in these events should be considered at the moment to prescribe groups.

Adolescent↗