PubMed Health⌕ Search

Biomedical subjects

E Edwards

Publications and source records attributed to E Edwards.

At least 37 records · Page 2Linked to original sources
PubMed1990

Effects of bilateral adrenalectomy on the induction of learned helplessness behavior.

In the learned helplessness model of depression, naive Sprague-Dawley rats are exposed to a 40-minute uncontrollable shock training and are subsequently tested in a shock escape paradigm. "Helpless rats" exhibit 11 to 15 failures in a 15-trial test while "nonhelpless" rats and naive controls score 0 to 5 failures in the same test. We report on the effect of bilateral adrenalectomy on the induction of learned helplessness. Most of the adrenalectomized rats (70%) became helpless whereas sham controls responded to the training and testing similarly to naive nonoperated rats (20% to 30% helpless). This increase in behavioral deficits after adrenalectomy was reversed by administration of corticosterone, the naturally occurring glucocorticoid in rat. We conclude that secretion from the adrenal cortex is necessary for the incorporation of a learned response after stress and that a dysregulation of the hypothalamic-pituitary-adrenal axis seems to be involved in helpless behavior.

Adrenalectomy↗
PubMed1989

Characterization of 5-hydroxytryptamine3 receptors in the medial prefrontal cortex: a microiontophoretic study.

The microiontophoretic application of the selective 5-hydroxytryptamine3 (5-HT3) agonist 2-methylserotonin suppresses medial prefrontal cortex cell firing. This effect is blocked by the 5-HT3 antagonists BRL 43694 and ICS205930, but not by metergoline or (+/-)-pindolol. Continuous microiontophoretic administration of magnesium chloride or the gamma-aminobutyric acidA antagonist SR 95103 did not alter 2-methylserotonin's suppressant action, suggesting that this effect is direct. Our results suggest that 5-HT3 receptors have a functional role in the medial prefrontal cortex.

Animals↗
PubMed1989

Effects of (+/-)-DOI on medial prefrontal cortical cells: a microiontophoretic study.

The relatively selective 5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [+/-)-DOI) ejected by microiontophoresis at low currents potentiates glutamate (GLU)-induced excitation and at higher currents (greater than 20 nA) invariably inhibits both spontaneous and GLU-induced activity of cells in the medial prefrontal cortex (mPFc). The inhibitory action of DOI is blocked by the 5-HT2 antagonists, ritanserin, metergoline and spiperone, but not other receptor antagonists. Microiontophoresis of 1 M Mg2+ for 5-20 min did not alter DOI's inhibitory effect suggesting that DOI's action is a direct one. These results show that DOI predominantly inhibits mPFc neuronal activity and this inhibitory action is mediated by 5-HT2 receptors.

Amphetamines↗
PubMed1989

Imipramine and tetrabenazine: effects on monoamine receptor binding sites and phosphoinositide hydrolysis.

Treatment of rats for 21 days with tetrabenazine, a drug which depletes monoamines and is used behaviorally to screen for antidepressants, significantly decreased 5-HT2 receptor density, increased alpha 1-adrenoceptor density but did not alter beta-adrenoceptor density in homogenates of frontal cortices labeled with [3H]ketanserin, [3H]prazosin and [3H]dihydroalprenolol, respectively. These effects were not opposite to those of the antidepressant drug imipramine which decreased both 5-HT2 and beta-adrenoceptor density and did not alter alpha 1-adrenoceptor density. Some evidence for antagonistic interactions between the two drugs was found in that imipramine partially prevented the tetrabenazine-induced increase in alpha 1-adrenoceptor density and tetrabenazine partially prevented the imipramine-induced decrease in beta-adrenoceptor density. Neither drug altered phosphoinositide hydrolysis coupled to alpha 1-adrenoceptors. While the effects of tetrabenazine are frequently attributed to its reserpine-like action of depleting monoamines, these results provide the first indication that tetrabenazine alters 5-HT2 and beta-adrenoceptor density in a manner different from that of reserpine.

Animals↗
PubMed1989

Surgery in a geriatric population.

A prospective audit of 1111 general surgical procedures undertaken on 1040 elderly patients (over 64 years) revealed a mortality of 3.5% in potentially viable patients. Aged patients (over 74 years) had twice the mortality of old patients (65-74 years). Emergency surgery carried a sevenfold risk factor which is greater than is usually described. Of those patients who died (n = 56) 20 had a laparotomy for surgically incurable disease. Although the four grades of surgeon achieved similar mortality rates (range 4-5.8%), senior surgeons performed more major procedures (Consultants, 40%; SHOs, 19%). There was a low supervision rate of SHOs (37/100 overall, and 9/19 major cases). Of the 26 patients dying from medical disorders 17 had a previous history of that disorder, and only nine of these patients were admitted to our high dependency care unit. We conclude that mortality rates in the elderly could be improved by encouraging elective surgery and avoiding diagnostic laparatomy in patients with incurable surgical disease. We also suggest that no inexperienced surgeon should operate unsupervised on any elderly patient who is in ASA category 4 or 5, or who undergoes major or intermediate surgery. Further, all elderly patients in ASA category 4 or 5, or those with previous medical problems who have major emergency procedures should be managed postoperatively in a high dependency care unit.

Age Factors↗
PubMed1988

Polyphosphoinositide hydrolysis in response to light stimulation of rat and chick retina and retinal rod outer segments.

Phosphoinositides of chick and rat retina were labelled with [3H]inositol. Exposure of retinal preparations to light for 30 s caused loss of labelled phosphatidylinositol 4,5-bisphosphate and to a smaller extent of the other phosphoinositides. Similar light-induced changes were seen when rod outer segment preparations were used and, when these were illuminated in calcium-free media, phosphatidylinositol 4,5-bisphosphate was the only lipid affected. No inositol 1,4,5-trisphosphate was seen after either 30 s or 5 s of illumination of retina or 30 s illumination of rod outer segments. It is concluded that this compound plays no direct part in vertebrate photoreceptor light transduction, though phosphoinositide metabolism might relate to adaptation mechanisms.

Animals↗
PubMed1988

Muscarinic receptors in preoptic area and hypothalamus: effects of cyclicity, sex and estrogen treatment.

Cholinergic muscarinic receptor binding was measured in the preoptic area (POA) and whole hypothalamus (HTH) of adult Sprague-Dawley rats using the tritiated antagonist quinuclidinyl benzilate ([3H]QNB) as the ligand. Binding of [3H]QNB expressed as fmol/mg protein was 30% higher in POA than in HTH from gonadectomized rats. Cyclic changes were observed in the POA with the highest binding at proestrus and the lowest binding at diestrus. In HTH, no significant changes occurred over the estrous cycle. Estrogen treatment (10 micrograms of estradiol benzoate (EB)/120 g b. wt./48 and 24 h before sacrifice) increased [3H]QNB binding by 42% in the POA and 17% in HTH, relative to the ovariectomized controls. The enhancement of [3H]QNB binding in POA as compared with controls was evident with both the filtration and the centrifugation methods, although binding levels were higher when centrifugation assay was used. A lower estrogen dose (2 micrograms EB/rat/48 and 24 h before sacrifice) which is routinely used to activate lordotic behavior in female rats increased muscarinic binding by 26% in the POA but had no appreciable effect in HTH. A significant sex difference was found in the ability of estrogen to induce [3H]QNB binding in the central nervous system (CNS). Estrogen was ineffective in altering [3H]QNB binding in either brain region of castrated males, although the level and pattern of cholinergic binding between untreated gonadectomized males and females were similar.2+ These data suggest that physiological changes in estrogen secretion over the estrous cycle are capable of modulating cholinergic muscarinic binding in the POA and these changes may be of physiological relevance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The effect of postoperative collateral ligament laxity in total knee arthroplasty.

Forty-seven patients who had been treated by 63 total knee arthroplasties were assessed at 12-84 months after the operation. The data were analyzed to determine if collateral ligament laxity had a detrimental effect on the clinical outcome. The Hospital for Special Surgery (HSS) score was used to make the clinical assessment and a modified HSS score, which excluded points awarded for laxity, was also used. Unidirectional (varus or valgus) and total (varus and valgus) laxity were used as a basis of analysis. None of the examined parameters produced results suggesting that lax knees were worse than stable knees. Indeed, knees with increasing laxity through the categories of mild and moderate showed better statistically significant results in HSS score and pain than those with lesser degrees of laxity. Seventy-five percent of the knees with unidirectional laxity were classified as excellent; only 38.5% of the stable knees were graded as excellent (p less than 0.01). Only 9% of the lax knees had complaints of pain; 38% of the stable knees were painful (p less than 0.05). No significant difference in functional score and walking ability was noted between the lax and the stable knees. Seventy-eight percent of the lax knees had a range of motion over 100 degrees; 62.5% of the stable knees achieved this range.

Adult↗
PubMed1987

Selective beta-antagonists are equally and highly potent at 5-HT sites in the rat hippocampus.

Serotonin (5-hydroxytryptamine, 5-HT) and various tryptamine-related drugs were equi-potent to known beta-antagonists in competition experiments of 125Iodo-cyanopindolol binding in the rat hippocampus. IC50 values for all the tryptamine related drugs (5,7-DHT, 5-MT, 5-MEO, DMT) were very similar to those obtained for (-)-propranolol, (+/-)-cyanopindolol, zinterol and atenolol and were all in the nanomolar range. Saturation experiments demonstrated that in the rat hippocampus, a subpopulation of serotonin recognition sites comprised 50% of 125I-CYP binding. The KD was 140 +/- 30 pM and the Bmax was 71 +/- 7 fmole/mg protein. This suggests that 125I-CYP binding studies for the quantitation of beta-adrenergic receptors should be re-evaluated and caution should be exercised in the choice of the displacing agent for the definition of non-specific binding. (+/-)-[125Iodo]cyanopindolol (I-CYP) has been used as a radioligand which binds with high affinity and specificity to beta-adrenoceptors (Engel, Hoyer, Berthold and Wagner, 1981). The reported low dissociation constant (27-40 pM) of 125I-CYP for beta-adrenoceptors in various tissues, in combination with its high specific radioactivity (2175 Ci mmole-1) allowed binding studies to be carried out with low protein and ligand concentrations. These factors have established 125I-CYP as the choice ligand for the quantitation of beta-adrenoceptors in our laboratory (Edwards and Henn, 1985).(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗
PubMed1986

A role for disulphide bridges in the protein core in the interaction of proteodermatan sulphate and collagen.

Proteodermatan sulphate from bovine skin retarded precipitation of fibrils from solutions of purified acid-soluble bovine skin collagen. The isolated protein core was as effective as the intact proteoglycan. Thermal denaturation leading to almost complete loss of the native secondary structure, (determined by circular dichroism spectroscopy to consist of about 60% beta structure) did not diminish the effect unless accompanied by reduction of disulphides, of which there were shown to be three per molecule. The reduced and alkylated protein core was totally ineffective. Electron-microscopy revealed a D-periodic arrangement of glycosaminoglycan on the surfaces of collagen fibrils precipitated in the presence of proteodermatan sulphate. Dermatan sulphate (with attached small peptide) prepared from the proteoglycan, had no effect on the rate of fibrillogenesis and was apparently not bound to the fibrils.

Animals↗
PubMed1986

Neurochemical and behavioral consequences of mild, uncontrollable shock: effects of PCPA.

The present experiments examined the role of the serotonergic system in the behavioral deficit produced by uncontrollable shock. In Experiment 1: Establishment of model, the behavioral potential of the Sprague-Dawley rat was defined. When exposed to mild uncontrollable stress such as a 0.8 mA electric footshock, a significant percentage of rats developed a shock escape deficit which was evident when subsequently placed in a shock escape paradigm. Serotonin depletion was produced by chronic treatment with p-chlorophenylalanine. Biogenic amine levels and 5-HT levels were monitored in various brain areas using HPLC. Following chronic treatment with PCPA, the shock escape capability of the Sprague-Dawley rat was assessed. The severe depletion of 5-HT in various brain regions was highly correlated with a dramatic improvement in the shock escape scores. Thus, the detrimental effects of exposure to a mild course of inescapable shock can be prevented by chronic treatment with PCPA. These experiments implicate the serotonergic system as a possible mediator of the "learned helplessness" phenomenon.

Animals↗
PubMed1984

Alpha-2-adrenergic receptors in avian spinal cord: increases in apparent density associated with the sympathetic preganglionic cell column.

Vertebrate spinal cord receives a dense and diversified catecholaminergic innervation from brainstem and diencephalon. Within the spinal gray, the densest terminations appear to be within the neuropil surrounding sympathetic preganglionic neurons (SPNs) in thoracic spinal cord. Results of recent iontophoresis investigations showed that several catecholamines and clonidine, an alpha-2 agonist, uniformly inhibited the maintained discharge activity of SPNs [19]. These experiments raised the possibility that the inhibitory effects might be mediated by activation of an alpha-2-adrenergic receptor. The present series of ligand binding studies provide biochemical evidence suggesting the presence of alpha-2-adrenergic receptors in the SPN cell column. Total specific binding (Bmax) of the radiolabeled agonists clonidine (CLO) and para-amino-clonidine (PAC) (at concentrations above and below apparent KDS) was significantly greater in thoracic spinal cord in comparison with cervical spinal cord (P less than 0.001). The elevated levels in thoracic spinal cord were entirely accounted for by increases in apparent receptor density in dorsal horn and the SPN cell column (inclusive of the adjoining intermediate spinal laminae) (P less than 0.005). Adrenergic receptor subtype specificity of [3H]PAC was tested in competitive inhibition experiments. The results confirmed that [3H]PAC is a preferential alpha-2 agonist in thoracic and cervical spinal cord, and indicated the following rank order of potency for its displacement: norepinephrine = yohimbine much greater than prazosin greater than propranolol.

Adrenergic alpha-Agonists↗
PubMed1984

Alpha 1- and alpha 2-adrenoceptor binding in the Dahl rat model of hypertension.

Dahl sensitive rats on a high salt diet (DSH group) developed significant elevations in blood pressure (BP). Sensitive rats maintained on a low salt diet (DSL group) and Dahl resistant rats on a high or low salt diet (DRH and DRL groups, respectively) remained normotensive. The DSH and DRH groups displayed a lower density of alpha 2-adrenoceptors (as measured with [3H]-clonidine) in the cerebral cortex than normotensive DSL and DRL groups. In contrast, the density of alpha 2-adrenoceptors in the medulla was significantly lower in the DSH group than the DSL group, but significantly higher in the DRH group compared to the DRL group. The density of alpha 1-adrenoceptors (as measured with [3H]-WB4101) in the hypothalamus was lower in the DSH group than the DSL group but greater in the DRH group than the DRL group. The results suggest that the sensitive and resistant lines can be distinguished by the density of alpha 1- adrenoceptors in the hypothalamus and medulla, respectively. The interactive effects of dietary NaCl and susceptibility to hypertension on adrenoceptors lend further support to the hypothesis that the genetic predisposition to hypertension is associated with a disruption in central adrenergic activity.

Adrenergic alpha-Antagonists↗