Systemic adrenergic actions on liver T-4 5' deiodinase differ considerably from those seen in vitro.
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Biomedical subjects
Publications and source records attributed to A Nauman.
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Pure adrenergic beta-action, brought about by long-term adrenaline + regitine application in rats, was able to increase liver T4-5'-deiodinase activity for 8 h (Nauman et al. 1984a). Long-term isoprenaline application without alpha-blocking yielded contrary results. One of the compensatory mechanism to be probably blamed could have been the very high endogenous adrenaline-levels (Porta et al. 1985). Simultaneous treatment with isoprenaline and alpha-methyltyrosinemethylester did not settle the problem since even then deiodinase activity was still drastically decreased. Two more components have been found which could very well be the reason for that "paradox beta-action" in vivo, namely very low glucose and insulin levels, both of which are known to influence deiodinase activity. In vivo--contrary to in vitro--it is seemingly not possible that catecholaminergic beta-action could increase the peripheral production of T3 unless general alpha-blocking took place.
Autologous bone marrow transplantation (ABMT) in chronic granulocytic leukemia (CGL) aims at reversing the acute or acceleration phases by injection of stem cells collected during the chronic phase. This study was designed to explain an unusual rate of delayed engraftment (50%) in our experience of ABMT in CGL patients. We investigated all the factors possibly responsible for abnormal perpetuation of aplasia following infusion of cryopreserved marrow stem cells. The study of CFU-gm recovery in 41 bags of frozen marrow from 25 patients revealed an overall deficiency with a mean CFU-gm recovery of 55 +/- 38% in CGL patients versus 73 +/- 15% in the control group (p less than 0.001). Our data also showed an inverse linear relation (r = -0.40, p less than 0.05) between CFU-gm concentration and recovery after freezing. A good CFU-gm recovery (greater than or equal to = 50%) was observed in 70% of cases when the concentration was less than 3700 CFU-gm/ml as compared to 30% of cases when the concentration was over 3700 CFU-gm/ml (p less than 0.001). The lack of improvement by diluting rich CFU-gm marrows to reduce CFU-gm concentration/ml, as well as the absence of relationship between CFU-gm recovery after freezing and nucleated cells concentration, suggest a particular fragility of CGL stem cells to freezing, probably related to their excessive amplification. At the present time, we strongly recommend that the highest possible dose of progenitor cells be cryopreserved, preferably at a low concentration, in patients with CGL, and particular attention devoted to the freezing procedure in each individual patient, with numerous appropriate efficiency tests.
Metabolic effects of Metipranolol, a new beta adrenergic blocking agent, have been studied in patients with ischemic heart disease, hyperkinetic syndrome, hyperthyreosis and in healthy subjects. Administration of the drug (30 mg per day for one week) resulted in the decrease of noradrenaline excretion, blood free fatty acid level, and in lowering of blood pressure and heart rate, particularly in patients with ischemic heart disease and hyperkinetic syndrome. These alterations were accompanied by alleviation of clinical symptoms. It is suggested that Metipranolol by suppressing the activity of sympathetic nervous system and thereby diminishing lypolysis, exerts favourable clinical effects, most probably related to diminution of myocardial oxygen consumption.
We have previously shown that acute coronary occlusion in the dog is often accompanied by increased adrenaline release into the blood. In the present study the consequences of this humoral reaction were studied in anaesthetised healthy mongrel dogs subjected to adrenaline infusion administered at a rate relevant to spontaneous release of this amine in coronary occlusion. Adrenaline was infused in a dose of 1.2 microgram.kg-1.min-1 for 4 h. Dogs receiving saline served as the control. Adrenaline administration led to the decrease in insulin/glucose ratio, to a significant fall in serum triiodothyronine and in blood pH. Free fatty acid levels doubled. Histochemically, a diminution in succinic dehydrogenase and ATPase activity in adrenaline-treated hearts was found. A significant fall in the activity of mitochondrial hexokinase in these hearts was detected spectrophotometrically. Electron microscopic study revealed alterations in the mitochondrial structure. These findings indicate that an excess of adrenaline in ammounts similar to that seen in experimental infarction leads to profound metabolic and hormonal disturbances and exerts a detrimental effect upon myocardium.
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