Schmidt's syndrome presenting with intrauterine growth retardation and postpartum addisonian crisis.
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Addison Disease↗
Biomedical subjects
A Angel
Publications and source records attributed to A Angel.
Specific effects of drugs at pressure: animal investigations.
The interactions of anaesthetics and other drugs with high pressure suggest that protection against the high pressure neurological syndrome (h.p.n.s.) can no longer be considered in terms of generalized non-specific mechanisms. The evidence from our work shows that anaesthetics may either protect, have no effect, or potentiate h.p.n.s. Structural analogues of the steroid anaesthetic Althesin have a protective effect against high pressure tremors in spite of the fact that they have no anaesthetic effects. Low doses of flurazepam are effective against tremor but can be antagonized by Ro 15-1788, which implies in this case a role for the benzodiazepine receptor complex. Pressure interactions with other drugs have included the classic anticonvulsants--which, in general, were relatively ineffective--and various agents perturbing the balance of specific neurotransmitter systems. Representative examples from different studies include 6-hydroxydopamine, muscimol, and sodium valproate. Finally, the potent protection against h.p.n.s. by 2-amino-phosphonoheptanoic acid, an antagonist with preferential action against excitation produced by aspartate and N-methyl-D-aspartate, provides the first evidence that enhanced excitatory amino acid neurotransmission may have an important role in the h.p.n.s.
Amino Acids↗
Chronic and acute administration of typical and atypical antidepressants on activity of brain noradrenaline systems in the rat thiopentone anaesthesia model.
A behavioural model sensitive to manipulation of brain noradrenaline systems and with characteristics of beta-receptor mediation has been developed using the duration of thiopentone anaesthesia in the rat. Acute and chronic administration of various antidepressant agents was examined. In the acute phase, (30 min prior to thiopentone) the noradrenaline uptake-inhibiting tricyclic drugs and viloxazine increased anaesthesia duration in a dose-dependent fashion. The atypical antidepressants trazodone, iprindole, and mianserin did this only weakly, while the dopaminergic and serotonergic uptake-inhibiting antidepressants (respectively bupropion, nomifensine, and zimelidine, fluoxetine) markedly shortened anaesthesia duration. Chronic administration (for 15 days) prolonged anaesthesia duration measured 2 or 5 days after the last drug injection for all tricyclic agents, for the atypical antidepressants mianserin, iprindole, fluoxetine, and zimelidine, and for viloxazine.
Anesthesia↗
Effects of starvation and plasma exchange on lecithin: cholesterol acyltransferase activity and cholesterol efflux in cholesterol-fed pigs.
The effects of starvation and of plasma exchange with a cholesterol-free substitute on efflux of tissue cholesterol and on lecithin: cholesterol acyltransferase (LCAT) activity in plasma and peripheral lymph were investigated in two pigs fed a cholesterol diet for 3-4 months. The pigs were labelled with i.v. [14C]cholesterol before plasma exchange or starvation. The cholesterol diet increased plasma total cholesterol concentration and LCAT activity in plasma and lymph, but had little effect on the rate of esterification of cholesterol in plasma or lymph. During cholesterol feeding, and when the animals were fed a normal diet, cholesterol esterification rates in plasma and lymph were much lower than the maximum rates achieved when LCAT was saturated with substrate, suggesting that LCAT in normal pig plasma and lymph is not saturated with substrate. Plasma exchange, carried out when the specific activity of tissue cholesterol exceeded that of plasma cholesterol, was followed by a brief rise in the specific activity of plasma cholesterol to a maximum value between the specific activities of muscle and adipose-tissue cholesterol, reflecting the transfer of radioactive cholesterol from tissue to plasma. During the rise in plasma total cholesterol specific activity there were no differences between the specific activities of low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol in plasma or lymph. Starvation had no effect on the plasma-cholesterol specific-activity curve. From about day 14 after labelling, cholesterol-specific activity decreased in the order: tissues greater than lymph greater than plasma. This suggests that the transfer of cholesterol from tissues to plasma was mediated by lipoproteins in the interstitial fluid.
Animals↗
Anaesthesia: the role of adrenergic mechanisms.
The beta-blocker propranolol administered intraperitoneally to rats prior to the barbiturate anaesthetic thiopentone caused a dose-dependent increase in anaesthesia duration. Sotalol, which only poorly crosses the blood-brain barrier, had no such effect, implying a central site of action. The selective beta 1-blockers, metoprolol and atenolol, did not alter thiopentone anaesthesia duration; implying that the effect of propranolol was mediated by a beta 2-receptor. The selective alpha 1-blocker prazocin increased thiopentone anaesthesia duration, while the alpha 1-agonist ST 587 decreased it. Since the alpha 1-agonist methoxamine, which only poorly crosses the blood-brain barrier, was ineffective, a central site of action is indicated. The alpha 2-agonist clonidine markedly increased thiopentone-anaesthesia duration, while the alpha 2-blocker yohimbine, shortened the duration. These effects were shown to be noradrenergic since they were blocked by prior depletion of brain noradrenaline using 6-hydroxydopamine. A model is proposed in which drug-induced alterations in the firing of locus coeruleus cells, or drug-induced changes in the postsynaptic effect of released noradrenaline, may be responsible for modulation of cortical arousal, wakefulness and the processing of sensory stimuli; thus affecting the duration of barbiturate anaesthesia.
Adrenergic alpha-Antagonists↗
Behavioural evidence that chronic treatment with the antidepressant desipramine causes reduced functioning of brain noradrenaline systems.
A behavioral system sensitive to the net functional activity of the locus coeruleus noradrenergic system, with characteristics of a beta-adrenoceptor mediated response, has been developed based on the duration of thiopentone anaesthesia in the rat. The effects of acute and chronic treatment with the tricyclic antidepressant desipramine (DMI) were determined. Acute DMI from 5 to 25 mg/kg increased thiopentone sleeping-time in a dose-dependent fashion. This was due to an action on noradrenergic systems, since it was mimicked by treatment with the selective neurotoxin 6-hydroxydopamine, which itself increased thiopentone sleeping-time and prevented any additional effect of DMI. Chronic treatment with DMI had no effect on thiopentone sleeping-time when carried out for 2 or 5 days but markedly prolonged it when carried out for 10 or 20 days, thus paralleling the time course of clinical action of the drug.
Animals↗
Brain noradrenaline and anaesthesia: further characterization of the beta-receptor.
The sleeping time induced by thiopentone in rats was markedly prolonged by the (-)-isomer of propranolol while the (+)-isomer was virtually without effect. Since the two isomers are equipotent in their membrane-stabilizing effects but the (-)-isomer is about seven to ten times more potent than the (+)-isomer in beta-blockade this suggests that the potentiation of barbiturate sleeping time is due to blockade of beta-adrenergic receptors. The centrally active beta-agonist, clenbuterol, shortened thiopentone-induced sleeping time in a dose-dependent fashion while the beta-agonist, salbutamol, which fails to cross the blood-brain barrier, was without effect. This suggests a central locus of action. Destruction of the noradrenaline system in the locus coeruleus with 6-hydroxydopamine prevented the effect of a racemic mixture of propranolol in elevating thiopentone-induced sleeping time, thus confirming a noradrenergic mechanism and indicating that the coerulear, rather than the medullary, noradrenaline fibres were involved. Thiopentone-induced sleeping time was potentiated by the selective beta 2 blocker ICI 118551 but not by the selective beta 1 blocker, metoprolol, thus characterizing the relevant beta-receptor type as beta.
Anesthesia↗
Brain noradrenaline and varieties of alternation learning.
Depletion of noradrenaline from the locus coeruleus system was effected by intraperitoneal injection of 6-hydroxydopamine to neonatal rat pups. Spontaneous, and two paradigms of rewarded alternation behaviour were examined in a T-maze. No change was seen in spontaneous alternation but marked impairment in acquisition of one of the two rewarded alternation tasks was found. It is concluded that powerful support is offered to previous results using intracerebral adult 6-hydroxydopamine administration.
Animals↗
Brain noradrenaline and anaesthesia: behavioural and electrophysiological evidence.
Neonatal administration of 6-hydroxydopamine to rat pups was used to deplete brain noradrenaline in the locus coeruleus projection system to less than 5% of normal and the response to barbiturate and non-barbiturate anaesthetics examined. The sleeping time in response to administration of thiopentone, pentobarbitone, methohexitone or hexobarbitone was markedly increased in 6-hydroxydopamine-treated rats, as it was for the non-barbiturates chloral hydrate and diisopropylphenol. The sleeping time for other non-barbiturates such as althesin, ketamine and ethyl carbamate (urethane) was not affected in noradrenaline-depleted rats. Similarly, an index of the evoked potential, recorded in the primary somatosensory cortex to supramaximal electrical stimulation of the forepaw, decreased more markedly with increasing doses of thiopentone in 6-hydroxydopamine-treated rats than in controls. Potentiation of the effect of diisopropylphenol on the evoked cortical response was also seen in noradrenaline-depleted rats while the effect of althesin did not differ. It is suggested that brain noradrenaline pathways originating from the locus coeruleus may play an important role in the duration and depth of anaesthesia resulting from barbiturate and some related agents.
Anesthesia, General↗
Interactions of gamma-aminobutyric acid and noradrenaline in the high pressure neurological syndrome.
The effects on the high pressure neurological syndrome (HPNS) of reducing brain noradrenaline (NA) levels were studied in adult rats. The onset of tremors and convulsions, which occur as pressure is increased, were used as endpoints for assessing the onset and severity of the HPNS. Neonatal treatment with 6-hydroxydopamine (6-OHDA; 100 mg kg-1 i.p. alternate days from birth for 2 weeks) which depleted brain NA, produced no change in the HPNS as assessed by the appearance of tremors and convulsions. A second series of NA-depleted rats and equivalent controls were treated with a GABA agonist, muscimol, 0.1 microgram intracerebroventricularly. Subsequently the rats were exposed to pressure and the onset and severity of the HPNS was assessed by observation of tremors and convulsions. A combination of NA depletion and intracerebroventricular injection of muscimol significantly raised the onset pressures for tremors and convulsions, i.e. delayed the appearance of the HPNS. These results are consistent with the HPNS being associated with a disturbance in the balance of two or more neurotransmitter systems, rather than simply an increase or reduction in levels of a single transmitter.
Aminobutyrates↗
Variations in intralipid tolerance in newborn infants.
Intravenous Intralipid tolerance tests (IVLTT) were done in 26 newborn infants of 26-40 wk gestational ages. The clearance constants (k2) ranged from 1.2-12.7 (%/min) after bolus injections given within 4.5 h (n = 12) or daily (n = 13). Significant variation (17-31%) occurred, similar to adults, and was unrelated to the time or dose given. Eleven infants received continuous Intralipid infusions for 10-24 h at a rate calculated to maintain a plasma Intralipid plateau concentration of 100 mg/dl. Nine infants did not exceed this optimal plasma level, although four could have tolerated more Intralipid. Two infants exceeded the ideal plasma concentration (greater than 100 mg/dl). All infants achieved and maintained plateaus within 5 h. Neither day-to-day variations nor the bolus dose used to establish clearance characteristics, accounted for the discrepancies in plateaus achieved. These studies identify some limitations of the IVLTT as a predictor of Intralipid utilization during continuous infusion, and the need for early monitoring of plasma Intralipid concentrations to optimize the therapeutic dose given to newborn infants.
Fat Emulsions, Intravenous↗
Familial deficiency of apolipoproteins A-I and C-III and precocious coronary-artery disease.
We studied two sisters 29 and 31 years old who had skin and tendon xanthomas, corneal clouding, and severe coronary atherosclerosis. Histologic examination showed collections of lipid-laden histiocytes in the skin. The patients' plasma cholesterol concentrations were 177 and 135 mg per deciliter (4.58 and 3.49 mmol per liter). Levels of high-density-lipoprotein cholesterol were 4 and 7 mg per deciliter (0.1 and 0.2 mmol per liter). Only traces of apolipoprotein A-I were detected in whole plasma. The plasma density fraction from 1.06 to 1.21 g per milliliter contained no high-density lipoprotein on high-pressure liquid chromatography, no apolipoprotein A-I on sodium dodecyl sulfate electrophoresis, and only traces of apolipoprotein A-I on radioimmunoassay. Apolipoprotein C-III was also not detectable. The activity of lecithin-cholesterol acyltransferase was 40 per cent of normal. The half-life of infused normal high-density lipoprotein was three days (normal, 5.8 days). The parents and children of these two patients had low levels of high-density-lipoprotein cholesterol and apolipoprotein A-I. These cases support the hypothesis that low concentrations of high-density lipoprotein promote atherosclerosis.
Adult↗
The effect of anaesthetic agents on cerebral cortical responses in the rat.
1. In rats, surgically anaesthetized with Urethane, an increase in the depth of anaesthesia upon administration of ethyl carbamate (Urethane), pentobarbitone sodium (Nembutal), thiopentone sodium (Intraval), althesin, ketamine, trichloroethylene, halothane, methoxyflurane, diethyl ether, ethyl-vinyl ether, cyclopropane, enflurane or chloroform resulted in a dose-dependent increase in the latency, the decrease in the amplitudes of the initial positive and negative components of the short latency cortical response to electrical stimuli applied to the forepaw. 2. The same changes were seen when starting from initially unanaesthetized rats and anaesthetizing them with Urethane. 3. With all the inhalational agents used these changes lasted for as long as the administration except with nitrous oxide where the changes in the cortical response were transient. 4. The tranquilizing agents diazepam, chlordiazepoxide, and haloperidol showed no such action. Chloral hydrate and chlorpromazine, on the other hand, produced moderate changes in the evoked cortical response similar to those seen with the other anaesthetic agents used.
Anesthesia, Inhalation↗
Sciatic nerve block by the anterior and posterior approach for operations on the lower extremity. A comparative study.
The results of the analgesic block of the lower extremity by means of an anterior (150 patients) or a posterior (114 patients) approach to the sciatic nerve, associated to a "3 in 1 block" were compared. The anterior approach technique was associated with a higher incidence of failures, insufficient analgesia and hence a higher demand for intraoperative analgesic and sedative drugs. Also tolerance to a pneumatic tourniquet over the proximal thigh was less than with the posterior approach. However, the sciatic nerve block by anterior approach granted a more prolonged analgesia. This technique was suitable for trauma patients immobilized in the supine position, for patients with skeletal traction on Zupinger frame, both for surgery and for closed reduction of lower extremity fractures.
Adolescent↗
The influence of thiopentone and alfathesin on succinylcholine-induced fasciculations and myalgias.
Thiopentone doses corresponding to 5.238 mg x kg-1, that is 2UD95 (UD95:unconsciousness dose 95) inhibit the intensity of succinylcholine-induced fasciculations compared with UD95. Alfathesin doses corresponding to 0.570 mg x kg-1, also 2UD95 (calculated as alphaxalone at a concentration of 9 mg/ml in alfathesin), do not have any greater effect on the degree of fasciculations compared to UD95. Furthermore, neither induction agent influences the incidence, distribution and duration of succinylcholine-induced myalgias. The inhibition of the degree of fasciculations caused by thiopentone is believed to be a consequence of a postsynaptic depressant effect of thiopentone at the neuromuscular junction. The evaluation of the degree of succinylcholine-induced fasciculations must take into consideration the dose of thiopentone administered at induction of anaesthesia.
Adult↗
The effects of hypothyroidism, age, and nutrition on LDL catabolism in the rat.
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Aging↗
The effects of trimethadione on pentetrazol-induced discharges of primary muscle spindle afferents from the hind limb of the rat.
1 Recordings have been made from primary muscle spindle afferents in split dorsal root filaments of rats anaesthetized with urethane. 2 Injection of pentetrazol (PTZ, 10 mg/kg) produced elevated discharge in the afferents with intact efferents without any charge in tension or electrical activity of the muscle of origin. 3 This elevated discharge was found to contain elements of both gamma d and gamma s activation. 4 Trimethadione (100 mg/kg), itself produced a transient increase in discharge and effectively suppressed PTZ-induced discharges of the afferents for at least 2 h. 5 These results are discussed in the context of established effects on sensory and motor systems.
Afferent Pathways↗
Exchange of free cholesterol between low density lipoproteins and human adipocytes.
Free cholesterol uptake from low density lipoproteins (LDL) by fat cells was investigated using exchange-labelled [1,2-3H]cholesterol-LDL and isolated human adipocytes, prepared by collagenase digestion of subcutaneous fat tissue biopsies. Radioactivity appeared in the cellular lipids within 2 min and accumulated at a slower rate approaching linearity for 3 h. At 5 and 120 min, 90% of the recovered cellular radioactivity was found in the bulk lipid fraction and the remainder was distributed among organelle fractions. Uptake of [3H]cholesterol was linearly related to substrate concentrations up to 5 micrograms unesterified cholesterol - LDL . mL-1. At higher concentrations up to 22 micrograms unesterified cholesterol - LDL . mL-1, [1,2-3H]cholesterol accumulated more gradually but did not reach a plateau. Metabolic inhibitors, sodium azide plus sodium fluoride, had no effect on radiocholesterol uptake. Native LDL and high density lipoprotein at equivalent unesterified cholesterol concentrations decreased [1,2-3H]cholesterol uptake, to a similar extent suggesting isotope dilution. The results demonstrate a rapid, receptor-independent uptake of cholesterol from LDL by adipocytes, consistent with an exchange mechanism. This process could explain the rapid labelling of adipose tissue cholesterol in vivo following intravenous administration of radiocholesterol and efflux of free cholesterol from adipose tissue during starvation.
Adipose Tissue↗