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Biomedical subjects

M Da Prada

Publications and source records attributed to M Da Prada.

At least 109 records · Page 6Linked to original sources

Retinal rhythms in photoreceptors and dopamine synthetic rate: and the effect of a monoamineoxidase inhibitor.

Autophagic degradation (AV) in rod inner segments undergoes a circadian rhythm that is dependent on light stimulation, being abolished in constant darkness, but persisting with dampened amplitude in constant light and reentrained after phase-shifts of the light--dark cycle. AV activity can be stimulated by light in vivo and in vitro. The monoamineoxidase type A inhibitor drug clorgyline phase delays the circadian rest-activity cycle. Clorgyline did not phase delay the rhythms of AV nor of disk-shedding, but significantly reduced AV rhythm amplitude. A rhythm of retinal dopamine (DA) level and synthetic rate persists in constant darkness, thus demonstrating the circadian nature of this rhythm. The existence of an endogenous rhythm of a putative retinal neurotransmitter may indicate some basic regulatory function of the DA system. Moreover, DA level and synthetic rate were significantly increased by clorgyline. Thus, the drug-induced reduction of retinal morphological parameters to light stimulation is paralleled by an increase of retinal DA levels. A functional relationship between the retinal DA system and photoreceptor metabolism remains to be established.

Animals↗

[Hermansky-Pudlak syndrome in a Valais village].

Amongst 13 subjects with albinism observed in a village in the Valais, 7 present the clinical and laboratory findings of the Hermansky-Pudlak syndrome. Because of the close family links and the numerous consanguine marriages present in the pedigree, it is probable that the 5 subjects who could not be examined also suffer from the same syndrome. It has an autosomal recessive mode of inheritance. In this isolate the gene and heterozygote frequencies are, respectively, 1:12 and 1:6. Clinically the hemorrhagic diathesis is moderate, the visual and cutaneous symptoms predominate. The platelet dysfunction results from a lack of storage of components (Ca++, nucleotides, amines) normally present in the dense granules. The lack of dense granules is demonstrated by electron and fluorescence microscopy. This structural anomaly is present in the megacaryocyte before individualization of the platelets. Giant melanosomes were found in skin melanocytes.

Abnormalities, Multiple↗

Plasma catecholamine concentrations in normotensive rats of different strains and in spontaneously hypertensive rats under basal conditions and during cold exposure.

Under basal conditions, the levels of circulating norepinephrine (NE) and epinephrine (E) were higher in normotensive Wistar rats of different origins than in Sprague-Dawley rats. Since the decline of 3H-NE concentration in the plasma after i.v. injection was similar in Wistar and in Sprague-Dawley rats, the higher levels of endogenous NE in the former strain probably reflect greater NE release from sympathetic nerve terminals. In normotensive Sprague-Dawley and Wistar rats, plasma NE rose to various extents during cold exposure (4 degrees C), depending on the basal plasma NE levels. Compared with normotensive Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR) had similar basal plasma E and NE concentrations, similar rates of 3H-NE disappearance, but more rapid increases to higher values of plasma NE during cold exposure. It is concluded that the basal rate of peripheral catecholamine release does not seem to be the main determining factor for arterial blood pressure in the various rat strains and that the sympathetic neuronal system of SHR is more responsive to cold exposure than that of WKY rats.

Animals↗

Melatonin synthesis by rabbit platelets.

Platelets of reserpinized rabbits, incubated in buffer containing tritiated 5-hydroxytryptamine (3H-5HT), have the ability to convert 3H-5HT into labeled compound(s) extractable with alkaline-chloroform. The bulk of the chloroform-extractable radioactivity showed a Rf value similar to authentic melatonin on silicagel thin-layer chromatography. The labelled product eluted with ethanol from the silicagel area where melatonin was suspected to reside was identified as melatonin by mass spectrometry and radioimmunoassay. Our in vitro experiments demonstrate that rabbit platelets are capable of converting 5-HT into melatonin apparently because they possess the enzymatic equipment necessary for this biosynthesis i.e. serotonin N-acetyltransferase and hydroxyindole-O-methyltransferase.

Animals↗

Rapid and sensitive single-step radiochemical assay for catechol-O-methyltransferase.

A simple, rapid and reliable radiometric assay for the determination of catechol-O-methyltransferase activity is described. The method is based on the conversion of catechol to [3H]guaiacol by catechol-O-methyltransferase in the presence of Mg2+, adenosine deaminase and S-adenosyl L-[methyl-3H]methionine. Incubation and direct extraction of [3H]guaiacol into organic scintillation fluid, as well as counting, are performed in the same standard scintillation vial. The assay is easy to perform and more sensitive than previous analogous procedures. The method has been applied to the assay of catechol-O-methyltransferase activity in discrete brain areas and also peripheral organs of rat and in human erythrocytes.

Adenosine Deaminase↗

Sympathetic immunoregulation: difference between high- and low-responder animals.

A quantitative relationship is reported between the magnitude of the immune response of rats to sheep red blood cells and diminution of splenic norepinephrine (NE). A decrease in concentration and content of NE in the spleen on day 3 after immunization was evident in both high- and low-responder animals, whereas a diminished concentration of NE persisted only in the high responders. This continuing NE diminution in high-responder animals is associated with increase in spleen weight, probably attributable to blood accumulation. These findings are consonant with the concept that the sympathetic nervous system is involved in immunoregulation.

Animals↗

Plasma catecholamines in rats exposed to cold: effects of ganglionic and adrenoreceptor blockade.

Exposure to cold (4 degrees C) of catheterized rats acclimated to 20 degrees C resulted in a progressive increase in plasma noradrenaline (NA) concentrations which reached values consistently more than twice the basal ones (20 degrees C) by about 30 min. No further increase in plasma NA levels were detected when the cold exposure was continued for 24 h. Plasma adrenaline (A) and dopamine levels did not change at any time studied. Adrenalectomized rats exposed to cold exhibited percent rises in plasma NA similar to those in intact rats. An increase in plasma A levels concomitant with that of NA was observed following exposure to cold of rats in which either basal catecholamine release was impaired by chlorisondamine or the vasoconstrictor response was impeded by phentolamine. Propranolol did not modify the acute neurosympathetic response to cold. Exposure to cold (4 degrees C) for short periods of time combined with the measurement of plasma catecholamines is proposed as a useful and reproducible method for studying a pure neurosympathetic response in the rat.

Adrenalectomy↗

Blood sampling by chronic cannulation technique for reliable measurements of catecholamines and other hormones in plasma of conscious rats.

An optimalized technique for chronic venous and arterial cannulation of rodents that permits repeated blood collections in unstressed, freely moving animals is presented. The indwelling catheter can also be used for chronic and/or acute drug administration in rats or other small laboratory animals, as well as for the recording of blood pressure and heart rate. The attachment device of minimal size is easily fixed on the head of the animals, allowing the additional implantation of a chronic cannula for intracerebral injections. No residual effects on the resting levels of plasma catecholamines (CA) were present 24-hr after surgery and anesthesia for implanting the cannula. No variations of plasma CA concentrations were observed at the different times of day examined or as a consequence of withdrawal of subsequent blood samples. Training the animals to be handled prevented the increase in plasma prolactin levels produced by decapitation; training had no influence on the decapitation-induced rises in plasma CA concentrations.

Animals↗

Plasma catecholamines in trained and untrained volunteers during graduated exercise.

Ten untrained subjects and nine trained cyclists were examined during graduated ergometric exercise in the supine position. The levels of epinephrine and norepinephrine in the blood as well as the heart rate and oxygen intake were determined. At submaximum levels, epinephrine, norepinephrine, lactate, and the heart rate are lower in tthe trained than in the untrained subjects; the relative oxygen intake shows no significant difference. The ergometric work capacity is approximately 30% higher in the trained cyclists. During maximum ergometric exercise, the plasma catecholamines, lactate, and the heart rate show no differences between the two groups; the oxygen intake is approximately 30% higher in the trained than in the untrained subjects. A direct relationship exists between catecholamine levels and lactate; however, this relationship becomes less exact during higher exercise intensities: In reference to the same catecholamine concentration, the lactate levels as well as the submaximum heart rates are higher in the trained than in the untrained subjects, the cause of which could be an increased beta-adrenoceptor sensitivity in the trained subjects.

Adult↗

Pharmacology of midazolam.

8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine (midazolam, Ro 21-3981, Dormicum) is an imidazobenzodiazepine whose salts are soluble and stable in aqueous solution. It has a quick onset and, due to rapid metabolic inactivation, a rather short duration of action in all species studied. Midazolam has a similar pharmacologic potency and broad therapeutic range as diazepam. It produces all the characteristic effects of the benzodiazepine class, i.e., anticonvulsant, anxiolytic, sleep-inducing, muscle relaxant, and "sedative" effects. The magnitude of the anticonflict effect of midazolam is smaller than that of diazepam in rats and squirrel monkeys, probably because a more pronounced sedative component interferes with the increase of punished responses. In rodents, surgical anaesthesia is not attained with midazolam alone even in high i.v. doses, whereas this state is obtained in monkeys. The drug potentiates the effect of various central depressant agents. Midazolam is virtually free of effects on the cardiovascular system in conscious animals and produces only slight decreases in cardiac performance in dogs anaesthetized with barbiturates. No direct effects of the drugs on autonomic functions were found, however, stress-induced autonomic disturbances are prevented, probably by an effect on central regulatory systems. All animal data suggest the usefulness of midazolam as a sleep-inducer and i.v. anaesthetic of rapid onset and short duration.

Anesthetics↗

Parathyroid hormone response to dopamine in cattle.

The effects of dopaminergic agonists on plasma levels of parathyroid hormone (PTH) have been studied in cattle. PTH increased within minutes in a dose-dependent manner during intravenous infusions of dopamine (DA) or epinine. Bromocriptine, in amounts that lowered plasma prolactin, inconsistently elevated PTH. Pimozide suppressed PTH responses to DA, whereas propranolol, phentolamine, phenylephrine, and atropine were ineffective. Plasma calcium and magnesium remained unaltered during DA and epinine infusions. Therefore DA appears to stimulate PTH secretion directly. After prolonged DA infusions, the secretion of PTH became resistant to both the administration of DA and isoproterenol, whereas the parathyroid glands remained responsive to a hypocalcemia. On the other hand, calcium suppressed PTH responses to DA. The results suggest that DA, beta-adrenergic agonists, and low calcium stimulate PTH secretion by separate but closely related mechanisms. Based on biochemical and histochemical observations on DA occurring in high amounts in bovine parathyroid glands, it is conceivable that this amine might stimulate PTH secretion at the level of the gland.

Animals↗