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Biomedical subjects

F M Williams

Publications and source records attributed to F M Williams.

At least 91 records · Page 5Linked to original sources
PubMed1990

The relationship between neutrophils and increased microvascular permeability in a model of myocardial ischaemia and reperfusion in the rabbit.

1. 111In-labelled neutrophils and 125I-labelled albumin were used to measure neutrophil accumulation and microvascular plasma protein leakage in the ischaemic/reperfused myocardium of anaesthetized rabbits. 2. A period of 30 min coronary artery occlusion followed by 3 h reperfusion resulted in an increase in both 111In and 125I counts in the area at risk (AR) of the myocardium. 3. Pretreatment of 111In-neutrophils in vitro with monoclonal antibody 60.3 directed against the CD18 antigen on neutrophils, followed by intravenous administration, significantly suppressed their accumulation into the AR myocardium. 4. Depletion of circulating neutrophils by use of anti-neutrophil serum or mustine hydrochloride did not affect plasma protein leakage into the AR myocardium. 5. Administration of the platelet activating factor (PAF) antagonist WEB 2086 (10 mg kg-1, i.v.) had no effect on the accumulation of 111In-neutrophils or on plasma protein leakage in the AR myocardium.

Anesthesia↗
PubMed1989

The efficacy of benorylate in postoperative dental pain.

The efficacy of a single pre-operative dose of benorylate (4 g) was determined in a double-blind, randomized, placebo-controlled parallel study in patients undergoing removal of a single impacted lower third molar. Patients treated with benorylate 4 g reported significantly less pain between 3-6 h after dosage than those treated with placebo. Overall pain scores at 6 h were significantly less in the benorylate group than the placebo group. However, overall pain scores at 12 h did not differ significantly between treatment groups. It is concluded from this study that a single dose of benorylate 4 g given immediately prior to the removal of an impacted lower third molar provides limited pain control during the postoperative period.

Acetaminophen↗
PubMed1989

Plasma aspirin esterase: the influence of old age and frailty.

Plasma aspirin esterase activity, expressed as nmol salicylate formed/ml plasma/min, was found to be similar in a group of healthy elderly adults, a group of young adults and a group of frail young adults, but was lower in a sample of frail elderly subjects. This was associated with reduced plasma albumin levels in healthy elderly subjects compared with young subjects and levels were lower still in the frail elderly group. Plasma cholinesterase also showed a trend towards reduced activity in the frail elderly subjects. As plasma aspirin esterase activity may influence the amount of circulating aspirin, these changes may have implications for the use of aspirin in frail elderly people.

Adult↗
PubMed1989

The relation of age to the acute effects of ethanol on acetanilide disposition.

The activity of the major drug-metabolizing enzymes, the mono-oxygenases, can be inhibited by an acute dose of ethanol. We set out to determine whether age has any relation to the degree of inhibition produced by ethanol, using acetanilide as a model substrate. Eight healthy young subjects (mean age 26 years) and eight healthy elderly subjects (mean age 72 years) were studied on two occasions, once receiving acetanilide alone and once acetanilide with 75 ml vodka (30 g ethanol). The clearance of acetanilide was significantly lower (p less than 0.05) in the elderly subjects at 27 +/- 3 l/h compared to 38 +/- 2 l/h in young subjects. No age-related differences in peak blood ethanol concentrations or ethanol elimination rates were noted. After ethanol, acetanilide clearance fell 18% to 31 +/- 3 l/h in young subjects (p = 0.05) and by 15% to 23 +/- 2 l/h in elderly subjects (p = 0.08). This suggests that the elderly do not suffer greater impairment of drug oxidation after acute ethanol ingestion than do the young.

Acetanilides↗
PubMed1989

Benorylate hydrolysis by human plasma and human liver.

1. Benorylate (4-acetamido phenyl-O-acetylsalicylate) hydrolysis in vitro by human plasma and by human liver microsomes and cytosol has been investigated. 2. Benorylate was hydrolysed by a route involving initial hydrolysis of the acetyl group to yield phenetsal followed by hydrolysis to paracetamol and salicylate. Hydrolysis via acetylsalicylate was minor. 3. Benorylate was more actively hydrolysed by liver cytosol than microsomes and about 10 times faster than plasma. 4. Following a single oral dose benorylate (4 g) to volunteers only salicylate and paracetamol were detected in the plasma. 5. The therapeutic effects of benorylate appear to be mediated by salicylate and paracetamol.

Acetaminophen↗
PubMed1989

Human liver and plasma aspirin esterase.

The plasma, in addition to the liver, is a major site of hydrolysis of aspirin. Human plasma and liver aspirin esterase activities in samples from a group of patients varied over a two fold range and there was a significant correlation between individual plasma and liver activities. Human liver aspirin esterase was present in the cytosolic and microsomal fractions. Cytosolic and microsomal enzymes had different activities and apparent affinities for aspirin.

Aged↗
PubMed1988

The acute and subchronic effects of ketoconazole on hepatic microsomal monooxygenases in the rat.

Female adult Wistar rats were treated with single or repeated doses of ketoconazole ranging from 10 mg/kg to 100 mg/kg. Single dose treatment produced inhibition of hepatic microsomal ethoxyresorufin O-deethylation (EROD) and aldrin epoxidation (AE) 2 hr after oral dosing. Twenty-four hours after a single dose, inhibition was still demonstrable after the low dose of 10 mg/kg, but at higher doses increased microsomal activity was apparent. After 7 days repeated dosing liver weight and microsomal protein content were increased in a dose-dependent fashion. EROD and AE were induced at all doses after repeated treatment when the increase in liver size was considered. These effects were seen at doses within the antimycotic therapeutic range and add support to the suggestion that reported drug interactions with ketoconazole in man are due to the effects of this drug on hepatic microsomal activity.

Animals↗
PubMed1987

Plasma esterase activity in patients with aspirin-sensitive asthma or urticaria.

Plasma aspirin esterase activity and cholinesterase activity were reduced in patients with aspirin sensitive asthma and aspirin sensitive urticaria compared to asthmatic and dermatological controls. Phenylacetate (non specific) esterase activities, were however unaltered in these patients. The reason for the lower activity is uncertain but it does not appear to be due to genetically determined lower cholinesterase or due to the avoidance of aspirin by sensitive patients. A low aspirin esterase activity may be a contributory factor in precipitating these aspirin sensitive reactions.

Aspirin↗
PubMed1987

7-Ethoxyresorufin deethylase (EROD) in human liver--the effect of alcoholic liver disease.

We have investigated the effect of alcoholic liver disease (ALD) on the metabolism of 7-ethoxycoumarin 0-deethylase in human liver microsomes. EROD activity was significantly reduced in tissue from ALD patients who smoked, compared to smoking controls. A similar trend was seen in non-smokers. These results have implications for the metabolism of environmental carcinogens.

Adult↗
PubMed1987

Effects of alterations in sympathetic nervous activity on the severity of reperfusion-induced arrhythmias in anaesthetised rats.

The effects of a number of interventions influencing sympathetic nervous activity on the severity of coronary artery reperfusion-induced arrhythmias in anaesthetised rats have been examined. Noradrenaline (0.1 microgram kg-1 min-1) reduced the mortality that usually occurred as a consequence of ventricular fibrillation. Isoprenaline (5 micrograms kg-1) did not significantly affect the severity of reperfusion-induced arrhythmias, although arrhythmias occurring during the 5-min period of ischaemia were exacerbated. The alpha-adrenoceptor antagonist nicergoline (0.25 and 0.5 mg kg-1 min-1) markedly suppressed both the ventricular tachycardia and fibrillation occurring upon release of the occlusion, whereas prazosin (1.0 mg kg-1) only slightly reduced the incidence of ventricular tachycardia. The beta-adrenoceptor antagonists atenolol and timolol did not significantly modify the severity of these reperfusion-induced arrhythmias. Pretreatment with reserpine (0.1 mg kg-1) or 6-hydroxydopamine (20 mg kg-1), which depleted myocardial catecholamine concentrations by 90%, had no effect on the indices of arrhythmic activity. Similarly, administration of L-thyroxine (1 mg kg-1) or propylthiouracil (50 mg kg-1) on 7 consecutive days prior to coronary artery occlusion did not alter the incidence of arrhythmias occurring upon reperfusion. Taken as a whole, these results do not suggest an important role for sympathetic nervous activity in the genesis of reperfusion-induced arrhythmias in anaesthetised rats.

Adrenergic alpha-Antagonists↗
PubMed1986

Major differences between lung, skin and liver in the microsomal metabolism of homologous series of resorufin and coumarin ethers.

Phenoxazone and a homologous series of its ethers (methoxy to octoxy plus benzyloxy), and coumarin and a series of its ethers (methoxy to propoxy), were metabolized by liver, lung and skin microsomes of normal adult female BALB/c mice. For each series of substrates, and with each tissue, clear structure-activity relationships were seen, relating metabolic activity to the length of the ether side-chain. With the coumarin series of substrates the structure-activity relationships were almost identical in the three tissues, with liver more active than lung and lung more active than skin. Liver, lung and skin microsomes each showed very different structure-activity relationships, however, for metabolism of the phenoxazone series of substrates. Benzyloxyphenoxazone was metabolized almost twice as fast in lung as in liver, but for the other phenoxazone substrates the activities were much greater in liver than in lung or skin. Liver, lung and skin microsomal propoxy- and benzyloxyphenoxazone dealkylase activities differed in their sensitivities to inhibition by metyrapone and alpha-naphthoflavone. The structure-activity relationship and inhibitor data for the phenoxazone substrates are consistent with a view that mouse lung and sking cyt. P-450 are predominantly similar to phenobarbitone-induced and 3-methylcholanthrene-induced forms of hepatic cyt. P-450 respectively. The results also show that the pattern of microsomal metabolism of xenobiotics in lung and skin cannot be reliably predicted from that in liver.

Animals↗
PubMed1986

Comparative efficacy of soluble aspirin and aspirin tablets in postoperative dental pain.

The efficacy of single doses (1.2 g) of soluble aspirin and aspirin tablets was determined in a randomised, placebo-controlled, double-blind, parallel study in 90 patients (45 females) with postoperative pain after removal of impacted lower third molars. Also investigated was the relationship between plasma aspirin esterase activity and overall pain scores after both aspirin preparations. Patients reported significantly less pain (p less than 0.001) after treatment with aspirin than after treatment with placebo. However, patients receiving soluble aspirin reported both an earlier onset and a longer duration of pain relief than those who received aspirin tablets. A significant correlation was observed between plasma aspirin esterase activity and overall pain scores after both soluble aspirin (r = 0.57, p less than 0.01) and aspirin tablets (r = 0.51, p less than 0.02). It is concluded that soluble aspirin is the preferred aspirin formulation for treating postoperative pain after third molar surgery and that plasma aspirin esterase activity is determinant of a patient's analgesic response to aspirin in postoperative dental pain.

Adolescent↗
PubMed1986

Activity of esterases in plasma from Ghanaian and British subjects.

We have measured aspirin esterase, cholinesterase, paraoxonase, and phenylacetate esterase activities in samples of plasma from British and Ghanaian subjects. Aspirin esterase, paraoxonase, and phenylacetate esterase activities were significantly lower in Ghanaians compared with British subjects. However, cholinesterase activities were similar in Ghanaian and British plasma samples. The lower esterase activities in Ghanaian plasma samples may result in higher circulating concentrations and greater pharmacological effects of drugs such as aspirin.

Aryldialkylphosphatase↗
PubMed1986

Ethoxyresorufin O-deethylation by human liver microsomes.

As a substrate for human liver microsomes, ethoxyresorufin appears to be metabolised by a group of cytochrome P450 isoenzymes which are inducible by cigarette smoking. Kinetic studies in microsomes from four human livers indicate that only one enzyme component is involved over the full substrate range. Ethoxyresorufin O-deethylation activity at both high and low substrate concentrations correlated with the high affinity component of ethoxycoumarin O-deethylation and of diphenyloxazole metabolism.

Adult↗
PubMed1986

Pharmacodynamics and pharmacokinetics of single doses of ketanserin and propranolol alone and in combination in healthy volunteers.

The potential interaction between ketanserin and propranolol has been investigated in eight healthy volunteers. Volunteers received single doses of placebo, propranolol (80 mg), ketanserin (20 mg), and propranolol (80 mg) plus ketanserin (20 mg) following a randomised double-blind regimen. A single dose of ketanserin had little effect on resting heart rate and blood pressure and the effects of propranolol and ketanserin in combination were similar to those of propranolol alone. The inhibition of exercise induced tachycardia by propranolol was not affected by ketanserin. The pharmacokinetics of propranolol elimination were not influenced by the concurrent administration of ketanserin, nor the pharmacokinetics of ketanserin by propranolol.

Adult↗
PubMed1986

Antiarrhythmic effects of DPI 201-106.

The cardiotonic agent DPI 201-106 (4-[3-(4-diphenylmethyl-1-piperazinyl-2- hydroxypropyl]-1H-indole-2-carbonitrile) which modifies the sarcolemmal Na+ channel gating system and has electrophysiological properties of class III antiarrhythmics was investigated for local anaesthetic and antiarrhythmic activity. The compound action potential amplitude of cat cervical vagus nerves in vitro was decreased by DPI 201-106 in a concentration-dependent manner, the IC50 being 1.82 X 10(-5) M. This was paralleled by a slowing in conduction velocity and demonstrates local anaesthetic effects. Ventricular fibrillation which occurs in response to coronary artery reperfusion in rats was prevented by intravenous infusions of 0.3 mg kg-1 min-1 of DPI 201-106. The arrhythmogenic intravenous doses of aconitine in rats were increased following pretreatment with DPI 201-106 in a dose-dependent manner. DPI 201-106 did not protect against ouabain-induced arrhythmias in guinea-pigs. The results demonstrate that DPI 201-106 has local anaesthetic effects and is a potential antiarrhythmic.

Aconitine↗