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Biomedical subjects

E D Hall

Publications and source records attributed to E D Hall.

At least 181 records · Page 10Linked to original sources

Effects of a single intravenous glucocorticoids dose on biogenic amine levels in cat lumbar spinal cord.

The effects of a single large intravenous dose of methylprednisolone on the steady state levels of dopamine, norepinephrine, and 5-hydroxytryptamine in cat lumbar spinal cord, as a function of dose (15, 30, or 90 mg/kg) and time (1 or 24 h) after administration, were examined by high performance liquid chromatography with electrochemical detection. Methylprednisolone produced a dose-related increase in the levels of dopamine and 5-hydroxytryptamine, but not norepinephrine, measured at 1 h. The effect of the single glucocorticoid dose was biphasic, however, as measurement of the three amines at 24 h showed each to be depressed below the levels found in untreated animals. The possible mechanistic basic and the significance of these glucocorticoid effects are discussed.

Animals↗

Correlation of methylprednisolone levels in cat spinal cord with its effects on (Na+ + K+)-ATPase, lipid peroxidation, and alpha motor neuron function.

Large intravenous doses of methylprednisolone sodium succinate are associated with biochemical and electrophysiological effects in the cat spinal cord which may be of therapeutic value in the treatment of spinal cord injury. The potentially beneficial effects of large doses of the glucocorticoid include: 1) an enhancement of spinal cord (Na + + K+)-ATPase activity; 2) an attenuation of lipid peroxide formation; 3) a hyperpolarization of motor neuron resting membrane potentials; and 4) an accelerated impulse conduction along the myelinated portion of the motor axon. Each of these is apparent with spinal cord tissue levels of methylprednisolone around 1.3 micrograms/gm wet weight, which are rapidly obtained following a single intravenous dose of 30 mg/kg. The half-life of methylprednisolone in cat spinal cord following a single intravenous administration, as well as the duration of its pharmacological actions, is roughly 3 hours. The data suggest that, in order to be of therapeutic value in the treatment of acute spinal cord trauma, early intervention with high-dose intravenous methylprednisolone (30 to 40 mg/kg) is necessary, followed by intravenous maintenance dosing of 15 to 20 mg/kg every 2 to 3 hours. The rationale and duration for this regimen are discussed.

Animals↗

Maximum capacity of the bovine liver to remove manganese from portal plasma and the effect of the route of entry of manganese on its rate of removal.

The rate of uptake of manganese by the liver was measured during infusions of manganese into either the visceral or the systemic circulation of four cows surgically prepared with cannulae in a mesenteric vein, the portal vein and a hepatic vein and in one carotid artery. In three experiments the maximum capacity of the liver to remove manganese from plasma was measured by infusing manganese chloride solution into a mesenteric vein at increasing rates for six hours. In two experiments the rate of uptake of manganese by the liver was determined during infusions of manganese chloride solution into a jugular vein for six hours at a constant rate. Virtually all the manganese infused into a mesenteric vein was cleared during its first pass through the liver, up to a maximum rate (mean +/- SEM) of 97.1 +/- 14.1 mumol per minute or 12.7 +/- 2.3 mumol per minute per kg of liver weight. However, when manganese was infused into a jugular vein at rates less than this maximum rate of uptake only approximately 50 per cent of the manganese in portal plasma was removed during a single passage through the liver.

Animals↗

Surgical procedure for modifying the duodenum in cattle to measure bile flow and the diurnal variation in biliary manganese, iron, copper and zinc excretion.

A surgical procedure is described for modifying the duodenum of cattle so that bile can be sampled and its rate of flow measured for long periods. In 12 steers, aged three months to three years and weighing between 50 and 650 kg, bile flow ranged from 2 to 12 ml per minute, the rate of flow increasing with bodyweight. The rate of flow expressed as ml per minute per 100 kg bodyweight decreased as bodyweight increased, the regression equation being in (ml per minute per 10 kg) = 1.65-0.0022 x where x = bodyweight (kg), r = 0.871. The mean concentrations of copper, iron, manganese and zinc in bile were 8.2, 6.2, 17.1 and 3.3 mumol per litre respectively. The concentration of iron was the least variable between the steers. The average total cholate concentration was 100 mmol per litre and total solids ranged from 5.4 to 7.2 per cent. Diurnal patterns in bile flow and trace element excretion were measured in four adult steers during a period of 38.5 hours. Although the rate of excretion of iron, zinc and copper and bile flow varied throughout the period, changes could not be associated with feeding or time of day. The concentration of manganese in bile and its excretion rate varied in a reproducible manner which may be related to feeding activity. The mean output of the four trace elements in bile from the four steers during 24 hours was, copper 37.7 mumol, iron 68.0 mumol, manganese 80.3 mumol and zinc 59.6 mumol.

Animals↗

Acute enhancement of spinal cord synaptosomal (Na+ + K+)-ATPase activity in cats following intravenous methylprednisolone.

The acute intravenous administration of high doses of methylprednisolone sodium succinate (15-90 mg/kg) to cats enhanced (Na+ + K+)-ATPase activity as much as 2-fold in synaptosomes prepared from lumbar spinal cord removed following drug administration. The effect was apparent within 5 min and was statistically significant at 1 h following a single injection of methylprednisolone 90 mg/kg. (Na+ + K+)-ATPase activity had returned to control levels by 24 h post-injection. The implication of these findings to the treatment of spinal cord trauma and the reported neurophysiological effects of glucocorticoids are discussed.

Animals↗

The maximum capacity of the bovine liver to excrete manganese in bile, and the effects of a manganese load on the rate of excretion of copper, iron and zinc in bile.

1. The maximum capacity of the bovine liver to excrete manganese in bile was determined in three Friesian-cross steers surgically prepared to allow bile flow-rate to be measured and samples collected. Plasma Mn concentrations were increased by infusing manganese chloride solutions into a jugular vein and the biliary excretion rates of Mn, copper, zinc and iron were measured. 2. The maximum capacity of the liver to excrete Mn in bile was exceeded at an infusion rate of approximately 4000 microgram Mn/min, and at this rate there was a significant decrease in the concentration of Cu, Fe and Zn in bile. The maximum concentration (mean +/- SE) of Mn in bile was 193 +/- 19 microgram/ml, and the maximum excretion rate (mean +/- SE) was 1210 +/- 130 microgram/min for three animals. There was no reduction in bile flow or evidence of live damage as a result of the infusions.

Animals↗

Glucocorticoid effects on serotonergic and noradrenergic facilitation of spinal monosynaptic transmission.

The ability of an intensive glucocorticoid regimen (i.e., triamcinolone diacetate, 8 mg/kg i.m./7 days) to modify the lumbar spinal monosynaptic reflex response to serotonergic and noradrenergic agents has been examined in unanesthetized acute spinal (C-1 sectioned) cats. Triamcinolone pretreatment enhances the 2N facilitatory actions of amitriptyline (AMIT), 5 mg/kg i.v., when given after D,L-5-hydroxytryptophan (5--HTP), 50 mg/kg i.v., as compared to untreated control preparations. Subsequent administration of methysergide, a serotonin receptor blocking drug, in a dose of 1 mg/kgh i.v. promptly and completely reverses the monosynaptic response increase by AMIT in untreated animals, but not in the glucocorticoid treated ones. In contrast, the monosynaptic facilitation normally produced in untreated preparations by methoxmine (MX), 1 mg/kg i.v., a centrally active noradrenergic agonist, is prevented as a result of triamcinolone dosing. These results demonstrate a glucocorticoid effect on spinal biogenic amine function such that serotonergic monosynaptic reflex activation is enhanced while noradrenergic reflex stimulation is depressed. Furthermore, they suggest that the elevations in plasma cortisol in certain cases of psychiatraic depression may; contribute to alterations in central biogenic amine synaptic activity.

5-Hydroxytryptophan↗

Effects of a single methylprednisolone dose on a facilitatory response of mammalian motor nerve.

Long-term glucocorticoid dosing directly enhances a facilitatory function of cat soleus motor nerve terminals. Posttetanic potentiation (PTP) of soleus contraction is a manifestation of this prejunctional facilitation. The present study demonstrates that the same enhancement of facilitation is produced with a single large intravenous dose methylprednisolone. The single dosing method, however, showed an initial suppression of facilitation that neared recovery in four hours. Thereafter, the characteristic augmentation of prejunctional facilitation emerged, peaking in 24 hours. Return to control required four days. Knowledge of this time course enabled centrally disconnected motor nerve endings to be identified as the site of both phases of the steroid action. Since the neuromuscular facilitation studied is equivalent to that triggered by neostigmine-like drugs, the results infer that the antimyasthenic effect of glucocorticoids may involve a direct action on motor nerve endings.

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