Biomedical subjects

J A Clements

Publications and source records attributed to J A Clements.

184 records · Page 11Linked to original sources

PubMedDate not supplied

N-acetylated endorphins in ovine anterior pituitary and neuro-intermediate lobe.

We have used an antiserum for immunohistochemistry and RIA/RP-HPLC which recognizes all fragments of N-acetylated endorphin (NacEP). In the rat neuro-intermediate lobe (N-IL), in addition to the N-acetylated forms of immunoreactive-beta-endorphin (ir-beta EP) already reported, we have demonstrated Nac beta EP as a minor component. In the sheep pituitary processing of beta EP is markedly different. In the anterior pituitary (AP), staining was indistinguishable with beta EP and NacEP antisera, in contrast with the rat where many fewer AP cells stained with the NacEP antiserum. Secondly, as in the rat, all N-IL cells stained with both antisera; on RP-HPLC, however, the major forms of NacEP in the sheep N-IL were Nac beta EP (approximately 40%), Nac beta EP (approximately 25%) and Nac beta EP (approximately 20%), with Nac beta EP (approximately 2%) as a minor component. A similar profile was seen on RP-HPLC of sheep AP. These data suggest that (1) patterns of processing in sheep AP are similar to those in N-IL, though the extent of acetylation is less and (2) in the sheep pituitary low molecular weight acetylated fragments predominate, in contrast with the rat.

Acetylation↗

PubMedDate not supplied

Immunoreactive beta-endorphin levels in plasma and pituitary tissue from genetically hypertensive and normotensive rats.

1. Levels of immunoreactive beta-endorphin were measured in neurointermediate lobes, anterior lobes and plasma from the Japanese and New Zealand strains of genetically hypertensive rats and their normotensive controls. 2. No significant differences were observed in beta-endorphin between the hypertensive and normotensive rats of the New Zealand strain. 3. The hypertensive rats of the Japanese strain showed significantly higher levels of beta-endorphin in neurointermediate lobe and lower levels in plasma than their normotensive controls. 4. These results suggest that the differences in beta-endorphin levels in the Japanese strain reflect a genetic difference not necessarily related to elevated blood pressure.

Animals↗

PubMedDate not supplied

Stress, dopaminergic blockade and median eminence-neurointermediate lobe catecholamine depletion: effects on hypothalamic, pituitary and plasma immunoreactive beta-endorphin.

We have compared immunoreactive beta-endorphin (ir-beta EP) levels in plasma, hypothalamus, anterior pituitary and neurointermediate lobe of adult female Sprague-Dawley rats, in studies in which levels of catecholamines were manipulated. Whole-brain catecholamines were manipulated by intraperitoneal haloperidol and/or bromocriptine; median eminence and neurointermediate lobe catecholamines were manipulated specifically and differentially by intravenous 6-hydroxydopamine (6-OHDA), with and without pretreatment with intraperitoneal desipramine; changes in amine neurons were assessed by fluorescence histochemistry. Haloperidol and 6-OHDA administration produced a selective reduction of neurointermediate lobe ir-beta EP, to levels equivalent to those seen with prolonged stress; the haloperidol effect was blocked by bromocriptine and the 6-OHDA effect by desipramine. Specific depletion of catecholamine nerve terminals in the median eminence and the neurointermediate lobe was associated with elevated plasma ir-beta EP, with no changes in pituitary or hypothalamic levels. These studies confirm and extend previous reports documenting that ir-beta EP levels in different tissues are modulated by different neural stimuli.

Animals↗

PubMedDate not supplied

Clinical pharmacokinetics of paracetamol.

In therapeutic doses paracetamol is a safe analgesic, but in overdosage it can cause severe hepatic necrosis. Following oral administration it is rapidly absorbed from the gastrointestinal tract, its systemic bioavailability being dose-dependent and ranging from 70 to 90%. Its rate of oral absorption is predominantly dependent on the rate of gastric emptying, being delayed by food, propantheline, pethidine and diamorphine and enhanced by metoclopramide. Paracetamol is also well absorbed from the rectum. It distributes rapidly and evenly throughout most tissues and fluids and has a volume of distribution of approximately 0.9L/kg. 10 to 20% of the drug is bound to red blood cells. Paracetamol is extensively metabolised (predominantly in the liver), the major metabolites being the sulphate and glucuronide conjugates. A minor fraction of drug is converted to a highly reactive alkylating metabolite which is inactivated with reduced glutathione and excreted in the urine as cysteine and mercapturic acid conjugates. Large doses of paracetamol (overdoses) cause acute hepatic necrosis as a result of depletion of glutathione and of binding of the excess reactive metabolite to vital cell constituents. This damage can be prevented by the early administration of sulfhydryl compounds such as methionine and N-acetylcysteine. In healthy subjects 85 to 95% of a therapeutic dose is excreted in the urine within 24 hours with about 4, 55, 30, 4 and 4% appearing as unchanged paracetamol and its glucuronide, sulphate, mercapturic acid and cysteine conjugates, respectively. The plasma half-life in such subjects ranges from 1.9 to 2.5 hours and the total body clearance from 4.5 to 5.5 ml/kg/min. Age has little effect on the plasma half-life, which is shortened in patients taking anticonvulsants. The plasma half-life is usually normal in patients with mild chronic liver disease, but its prolonged in those with decompensated liver disease.

Acetaminophen↗