Extra-vesicular binding of noradrenaline and guanethidine in the adrenergic neurones of the rat heart: a proposed site of action of adrenergic neurone blocking agents.
1 The binding and efflux characteristics of [14C]-guanethidine and [3H]-noradrenaline were studied in heart slices from rats which were pretreated with reserpine and nialamide. 2 Binding of both compounds occurred at extra-vesicular sites within the adrenergic neurone. After a brief period of rapid washout, the efflux of [14C]-guanethidine and [3H]-noradrenaline proceeded at a steady rate. The efflux of both compounds appeared to occur from a single intraneuronal compartment. 3 (+)-Amphetamine accelerated the efflux of [14C]-noradrenaline; this effect was inhibited by desipramine. 4 Unlabelled guanethidine and amantadine also increased the efflux of labelled compounds. Cocaine in high concentrations increased slightly the efflux of [14C]-guanethidine but not that of [3H]-noradrenaline. 5 Heart slices labelled with [3H]-noradrenaline became refractory to successive exposures to releasing agents although an appreciable amount of labelled compound was still present in in these slices. 6 It is suggested that [14C]-guanethidine and [3H]-noradrenaline are bound at a common extravesicular site within the adrenergic neurone. Binding of guanethidine to the extra-vesicular site may be relevant to its pharmacological action, i.e., the blockade of adrenergic transmission. (+info
Long-term effects of N-2-chlorethyl-N-ethyl-2-bromobenzylamine hydrochloride on noradrenergic neurones in the rat brain and heart.
1 N-2-Chlorethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP 4) 50 mg/kg intraperitoneally, produced a long-term decrease in the capacity of brain homogenates to accumulate noradrenaline with significant effect 8 months after the injection. It had no effect on the noradrenaline uptake in homogenates from the striatum (dopamine neurones) and on the uptake of 5-hydroxytryptamine (5-HT) in various brain regions. 2 In vitro DSP 4 inhibited the noradrenaline uptake in a cortical homogenate with an IC50 value of 2 muM but was more than ten times less active on the dopamine uptake in a striatal homogenate and the 5-HT uptake in a cortical homogenate. 3 DSP 4 (50 mg/kg i.p.) inhibited the uptake of noradrenaline in the rat heart atrium in vitro but this action was terminated within 2 weeks. 4 DSP 4 (50 mg/kg i.p.) cuased a decrease in the dopamine-beta-hydroxylase (DBH) activity in the rat brain and heart. The onset of this effect was slow; in heart a lag period of 2-4 days was noted. In brain the DBH-activity in cerebral cortex was much more decreased than that in hypothalamus which was only slightly affected. A significant effect was still found 8 months after the injection. The noradrenaline concentration in the brain was greatly decreased for at least two weeks, whereas noradrenaline in heart was only temporarily reduced. 5 The long-term effects of DSP 4 on the noradrenaline accumulation, the DBH activity and noradrenaline concentration in the rat brain were antagonized by desipramine (10 mg/kg i.p.). 6 It is suggested that DSP 4 primarily attacks the membranal noradrenaline uptake sites forming a covalent bond and that the nerve terminals, as a result of this binding, degenerate. (+info
Myocardial uptake of digoxin in chronically digitalized dogs.
1 The time course of myocardial uptake of digoxin, increase in contractility and changes in myocardial potassium concentration was studied for 90 min following an intravenous digoxin dose to long-term digitalized dogs. 2 Nineteen dogs were investigated by the use of a biopsy technique which allowed sampling before and after administration of digoxin. 3 Ten minutes after administration of digoxin the myocardial concentration increased from 60 to 306 nmol/kg tissue, the myocardial concentration of digoxin was significantly lower (250 nmol/kg tissue) after 30 min and then increased again. 4 The transmural myocardial distribution of digoxin was uniform before and 90 min after administration of digoxin in long-term digitalized dogs but at 10 min after administration, both the subepicardial and the subendocardial concentration of digoxin were significantly lower than that of the mesocardial layer. 5 During the first 10 min the dp/dtmax increased to 135% of the control level. The increase remained unchanged during the rest of the study. 6 Myocardial potassium decreased throughout the study. 7 The M-configuration of the myocardial uptake curve and the non-uniformity of myocardial distribution of digoxin observed at 10 min after administrating digoxin to long-term digitalized dogs indicate that the distribution of myocardial blood flow may be changed during chronic digitalization. (+info
Infleuce of dietary levels of vitamin E and selenium on tissue and blood parameters in pigs.
Eighteen barrows approximately three weeks of age were used in a 3 X 3 factorial arrangement to investigate the effect of level of supplemental vitamin E and selenium on tissue and blood parameters. Tissue selenium concentrations increased in a quadratic manner with increased selenium intake with kidney tissue containing considerably greater concentrations than liver, heart or muscle. Supplementation of the diet caused a three-fold increase in serum selenium within the first week with a slight tendency to further increases in subsequent weeks. Serum vitamin E of unsupplemented pigs declined by fifty percent during the experiment, whereas supplemental vitamin E resulted in increased serum vitamin E. There was a considerable viration in percent peroxide hemolysis. Correlation of -0.63 between percent peroxide hemolysis and vitamin E intake and -0.85 between percent peroxide hemolysis and serum vitamin E were observed. (+info
Pathological changes in chickens, ducks and turkeys fed high levels of rapeseed oil.
Rations containing 25% of either regular rapeseed oil (36% erucic acid), Oro rapeseed oil (1.9% erucic acid), soybean oil or a mixture of lard and corn oil were fed to chickens, ducks and turkeys. The regular rapeseed oil ration caused growth depression, increased feed conversion and anemia in all species. All the ducks and some of the chickens fed the regular rapeseed oil ration died. These dead birds were affected with hydropericardium and ascites. No deaths in the turkeys could be attributed to the regular rapeseed oil ration but some turkeys fed this ration had degenerative foci characterized by infiltrations of histiocytic and giant cells in the myocardium. Severe fatty change in the heart, skeletal muscles, spleen and kidney was found at an early age in all birds fed the regular rapeseed oil ration. Less severe fatty change but no other lesions were found in birds fed the Oro rapeseed oil and soybean oil rations. (+info
Systemic infection with Alaria americana (Trematoda).
Alaria americana is a trematode, the adult of which is found in mammalian carnivores. The first case of disseminated human infection by the mesocercarial stage of this worm occurred in a 24-year-old man. The infection possibly was acquired by the eating of inadequately cooked frogs, which are intermediate hosts of the worm. The diagnosis was made during life by lung biopsy and confirmed at autopsy. The mesocercariae were present in the stomach wall, lymph nodes, liver, myocardium, pancreas and surrounding adipose tissue, spleen, kidney, lungs, brain and spinal cord. There was no host reaction to the parasites. Granulomas were present in the stomach wall, lymph nodes and liver, but the worms were not identified in them. Hypersensitivity vasculitis and a bleeding diathesis due to disseminated intravascular coagulation and a circulating anticoagulant caused his death 8 days after the onset of his illness. (+info
Variations in 35SO4 incorporation into glycosaminoglycans along canine coronary arteries. A possible index of artery wall stress.
Focal areas of accentuated wall stress along the course of canine coronary arteries may be revealed by the level of 35SO4 incorporation into glycosaminoglycans (GAG). In the anterior descending artery, 35SO4 incorporation in higher in the proximal than in the distal region and may be extraordinarily high as the vessel enters a proximally located muscle bridge and at the takeoff region of multidirectional branches. In the circumflex artery, the incorporation also is higher in the proximal than in the distal region and is high at the genu where the posterior descending artery forms. There are differences in uptake of 35SO4 in vessels even when the arteries arise from the same vascular bed.this was shown by the higher incorporation in the left coronary artery than in the right coronary artery. A general anatomical agreement exists between these sites of high 35SO4 incorporation and previously described locations of interval elastic disruption ans proliferation of intimal connective tissue in the dog. (+info
Anti-heart autoantibodies in ischaemic heart disease patients.
One hundred and ninety-nine ischaemic heart disease (IHD) patients were studied with regard to the prevalence of anti-heart autoantibodies (AHA). The incidence of AHA in IHD patients was 1%: one out of 102 patients who suffered acute myocardial infarction (AMI), one out of seventy-two patients who suffered from acute coronary insufficiency (ACI), and none out of twenty-five patients with other signs and symptoms of IHD, had AHA in their sera. An additional 2% of patients who suffered from AMI developed detectable antibody levels during a follow-up period of 15 days. In comparison,, 53% of patients (eight out of fifteen) who underwent heart surgery and who had no AHA prior to operation, developed these antibodies in their sera during 1-2 weeks following operation. (+info