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Biomedical subjects

K Woodhouse

Publications and source records attributed to K Woodhouse.

At least 19 recordsLinked to original sources
PubMed1996

Age-related changes in O-deethylase and aldrin epoxidase activity in mouse skin and liver microsomes.

The metabolism of three model substrates for the cytochrome P450 dependent mono-oxygenase enzyme system (P450-MMO) was studied in microsomes isolated from skin and liver of young adult and senescent C57B1/6J mice. The substrates chosen were aldrin (AE), 7-ethoxycoumarin (EOC), and 7-ethoxyresorufin (EOR). Both EOC and EOR activities were lower in senescent skin. By contrast, no-age related changes were seen in senescent liver. AE was similar in young and old, in both tissues. We suggest that some important age-related differences in cutaneous xenobiotic metabolism do occur, but that these are not mirrored by hepatic differences, and are substrate specific. Previous work from these laboratories would also suggest significant species differences.

Aging↗
PubMed1995

The relationship between age and cutaneous aryl hydrocarbon hydroxylase (AHH) activity.

Aryl hydrocarbon hydroxylase (AHH), a component of the mixed-function oxygenase system, has been identified in liver and in many extrahepatic tissues, including the skin. In this study, the effect of ageing on cutaneous AHH activity in both male and female Wistar and Brown Norwegian rats of two age groups (average ages being 44 and 130 weeks) was assessed using benzo(alpha)pyrene as substrate and by measuring the formation of the fluorescent metabolite 3-hydroxybenzo(alpha)pyrene. Results show that cutaneous metabolism of polycyclic aromatic hydrocarbons does not change between young adulthood and senescence in either male or female rats. Sex-related differences did occur, however, and may be explained, partly, by the existence of different molecular forms of cyt-P450. In conclusion, age does not appear to be a major determinant of basal cutaneous AHH activity in rats.

Aging↗
PubMed1995

Percutaneous endoscopic gastrostomy in geriatric patients: attitudes of health care professionals.

This study investigated, by questionnaire, the attitudes of geriatricians, speech therapists, dieticians, and nurses towards feeding by percutaneous endoscopic gastrostomy (PEG). The final response rate from a total of 199 questionnaires sent to this group was 75%. According to 95 (64%) of the respondents, the decision to use PEG feeding was reached by a multidisciplinary team approach and commonly involved carers as well as the patients. The quality of life was the single most important factor influencing this decision. PEG feeding was felt to be indicated in non-dysphagia-related malnutrition by 98 (66%) and in dementia with rejection of oral feeding by 69 (47%) of the respondents. It was felt by 39 (55%) of the nurses and by 32 (42%) of the other professionals that patients with dementia in long-term care who are established on nasogastric feeding should be converted to PEG feeding. This raises several ethical and resource issues.

Attitude of Health Personnel↗
PubMed1994

The use of percutaneous endoscopic gastrostomy (PEG) in 161 consecutive elderly patients.

Over the period 1 April 1990 to 31 December 1992, a total of 179 PEG procedures were performed on 161 elderly patients, mean age 79 years (range 53-99). In most (141) patients, the indication was neurological dysphagia (usually stroke), but in 20 the tube was inserted to attain adequate nutritional support. Thirty-day fatality was 20% overall, but in those who underwent PEG only for nutritional support, survival was poor--only 20% at 30 days. Almost all deaths were a result of progression of the original illness. Only one procedure-related death occurred. Fifty-six complicating episodes occurred in 20 (12%) patients, the majority being minor. The commonest adverse event was PEG site infection. PEG is a useful and in general well tolerated procedure in geriatric practice, but careful patient selection is essential; in particular its use as a nutritional adjunct in frail patients needs careful evaluation.

Adult↗
PubMed1994

Plasma aspirin esterase activity in elderly patients undergoing elective hip replacement and with fractured neck of femur.

Plasma aspirin esterase activity was measured in eight elderly patients undergoing elective hip replacement, and in 11 presenting with femoral-neck fracture. Elective hip surgery was associated with a marked and significant decline in esterase, from 330 +/- 35.9 (SE) (nmol salicylate/ml plasma/min) pre-operatively to 236 +/- 35.6 on the third post-operative day, and returning to normal (359 +/- 24.3) at recovery phase. Patients with fractured neck of femur showed a depressed esterase activity on admission (221 +/- 12.7), rising towards normal (290 +/- 15.4) on recovery. All of these changes were accompanied by a marked acute-phase response, both to injury and surgery. The data suggest that elderly patients experiencing injury or undergoing surgery may have significantly impaired drug metabolism, at least as far as this enzyme is concerned.

Aged↗
PubMed1994

Age, smoking and the activity of the mono-oxygenase aryl hydrocarbon hydroxylase in isolated human peripheral blood monocytes.

Age-associated changes in the microsomal mono-oxygenase enzyme, aryl hydrocarbon hydroxylase (AHH), were investigated in peripheral blood monocytes isolated from young and elderly subjects. Young subjects were selected from the age group < 35 years; elderly subjects were > 70 years. AHH activity, expressed as nM 3-hydroxy benzopyrene formed/10(6) cells/h of incubation, was similar in young and elderly non-smokers (elderly = 6.7 +/- 1.8; young = 9.1 +/- 0.9; p > 0.05). In smokers, contrary to some previous reports, AHH activity was not significantly higher than in non-smokers of similar age (elderly smokers = 8.6 +/- 1.0; young smokers = 10.5 +/- 2.4; p > 0.05). There was no significant difference between young and elderly smokers (p > 0.05). We conclude that: (a) AHH activity is similar in young and old non-smoking individuals; (b) no significant differences were detected in in vivo induction of this enzyme activity between smokers and non-smokers.

Adult↗
PubMed1992

Drugs and the liver. Part III: Ageing of the liver and the metabolism of drugs.

The clearance of many drugs by the liver is reduced in the elderly, and this accounts, at least in part, for the greater frequency of adverse drug reactions in this population. Ageing in experimental animals is accompanied by a decline in the activities of certain microsomal monooxygenase enzymes; this has been said to be the reason for decreased drug elimination. However, recent data suggests that this is probably not the case in humans. Reduced size and blood flow are important features of the ageing liver, and probably account for most of the age-related changes in drug metabolism. Major decrements in hepatic function do occur in frail elderly individuals, although the mechanisms underlying this are at present unclear. Future studies of drug metabolism and ageing must carefully define patient groups to allow full interpretation of data.

Aging↗
PubMed1992

Dose dependent induction of the microsomal monooxygenase aryl hydrocarbon hydroxylase in isolated peripheral blood monocytes: the influence of age.

The induction of the microsomal monooxygenase benzo(alpha)pyrene hydroxylase was investigated in isolated peripheral blood monocytes from young and old donors, after exposure to different concentrations of benzanthracene as an inducing agent. The sensitivity of the cells to the inducing stimulus was not dependent on the age of the donor. The mechanisms underlying impaired monooxygenase induction in the elderly remain to be clarified.

Adult↗
PubMed1991

The effect of caffeine on postprandial hypotension in the elderly.

In a double-blind, randomized trial the effects of caffeinated and decaffeinated drinks on postprandial hemodynamic and neurohumoral changes were studied in seven fit, elderly subjects after a standard 2.4MJ meal. There was a significant difference in supine postprandial systolic blood pressure between the placebo and caffeine phases (P less than 0.01); at 60 minutes, supine systolic blood pressure had fallen 14 mmHg [95% confidence interval (CI)-7 to-21 mmHg, p less than 0.01) after placebo, but was unchanged after caffeine (+9 mmHg, CI 0 to 18 mmHg, NS]. Similar differences between placebo and caffeine were seen in erect systolic and diastolic blood pressure (P less than 0.01), although orthostatic tolerance was maintained throughout each study period. Postprandial plasma noradrenaline levels were higher (P less than 0.02) and the increase greater (P less than 0.02) after caffeine than after placebo. Caffeine administered at the end of a standard test meal prevents the postprandial fall in blood pressure in fit, elderly subjects. The clinical relevance of this finding has yet to be determined, but it may offer a simple remedy for patients with symptomatic postprandial hypotension.

Aged↗
PubMed1991

The effect of age on glucuronidation and sulphation of paracetamol by human liver fractions.

Glucuronidation and sulphation were studied in vitro in human liver samples from 22 subjects aged 40-89 years using paracetamol as substrate. There was no significant correlation with age for the activity of either enzyme pathway. These results provide further evidence that age per se does not have a major effect on the activities of hepatic metabolising enzymes.

Acetaminophen↗
PubMed1990

The kinetics of plasma aspirin esterase in relation to old age and frailty.

The kinetics of the phase I enzyme aspirin esterase were estimated in plasma from ten young volunteers, seven healthy elderly volunteers, and in ten frail elderly subjects. Maximal reaction velocity at enzyme saturation (vmax) was similar in young and healthy elderly volunteers, but was significantly reduced in the frail elderly. The Michaelis constant (Km) was similar in all three groups. The results suggest that impaired in vitro aspirin metabolism in frail elderly people is due to a reduction in the quantity of enzyme present, rather than a qualitative change in enzyme proteins.

Adult↗
PubMed1989

Bladder irrigation or irritation?

Exfoliation rates of urothelial cells following bladder irrigation were studied in patients with long-term indwelling catheters and chronic urinary tract infections (UTI). The irrigations were associated with an increased shedding of urothelial cells. Ultrastructural studies of these cells demonstrated increased disruption when compared with those obtained from normal subjects without catheters or chronic infection. The findings suggest that bladder irrigation further damages the already disrupted urothelium, which may in turn increase the predisposition of the bladder to the recurrent infections, commonly associated with patients who have indwelling urinary catheters. Bladder irrigation methods and the indications for their use require reassessment.

Aged↗
PubMed1986

Oxidation of tricyclic antidepressant drugs, debrisoquine and 7-ethoxyresorufin, by human liver preparations.

Data obtained from human studies in vivo show that the dispositions of the tricyclic antidepressant drugs desmethylimipramine (DMI) and nortriptyline are related to the debrisoquine hydroxylation phenotype. To obtain insight into the enzymic mechanisms behind this, the metabolism of debrisoquine and antidepressant drugs by human liver preparations have been studied. The 2-hydroxylation of DMI in vitro correlates with the 4-hydroxylation of debrisoquine among various livers (rs = 0.90). Debrisoquine inhibits DMI hydroxylation competitively, and DMI inhibits debrisoquine hydroxylation, suggesting that DMI hydroxylation is catalysed by the debrisoquine hydroxylase in human liver. By monitoring the hydroxylation of DMI in various fractions during separation and purification of cytochrome P-450 from human liver microsomes we have purified a cytochrome P-450 which efficiently hydroxylates this drug. The apparently electrophoretically homogeneous enzyme had a molecular weight of 51,500 and hydroxylated DMI and debrisoquine at rates of up to 0.95 and 0.45 nmol/min . nmol P-450, respectively. This is probably the major debrisoquine hydroxylating cytochrome P-450 in man. Nortriptyline 10-hydroxylation correlates strongly (r = 0.96) with debrisoquine hydroxylation in human liver microsomes. Nortriptyline inhibits DMI-hydroxylation competitively, and the drug also inhibits the 4-hydroxylation of debrisoquine. Thus it is probable that nortriptyline is hydroxylated by debrisoquine hydroxylase. Imipramine N-demethylation did not correlate significantly (P greater than 0.1) with debrisoquine hydroxylation among microsomes from nine livers. However, if a liver from a subject, which was a poor metabolizer of debrisoquine in vivo, was included, a correlation was obtained (r = 0.79, P less than 0.01, N = 10). Imipramine demethylation also correlated with DMI-hydroxylation only if the 'poor metabolizer' liver was included (r = 0.75, P less than 0.05, N = 10). Debrisoquine inhibited imipramine demethylation competitively. The data indicate that imipramine can interact with debrisoquine- and DMI-hydroxylase, but it is uncertain if this enzyme plays an important quantitative role in its demethylation. Ethoxyresorufin O-deethylation correlated with DMI hydroxylation (r = 0.80) in human liver preparations, and DMI inhibited the former reaction in what is probably a mixed competitive-non-competitive inhibition. Liver preparations from a subject who was a poor oxidizer of debrisoquine both in vivo and in vitro had unusually low capacity to metabolize ethoxyresorufin. Thus ethoxyresorufin, at least partly, seems to interact with an enzyme that can metabolize DMI in human liver.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1985

Comparative metabolism of debrisoquine, 7-ethoxyresorufin and benzo(a)pyrene in liver microsomes from humans, and from rats treated with cytochrome P-450 inducers.

The metabolism of debrisoquine, 7-ethoxyresorufin and benzo(a)pyrene has been studied in human liver microsomes. There was a significant correlation (r = 0.70, P less than 0.05) between debrisoquine hydroxylation and 7-ethoxyresorufin 0-deethylation among various livers, and debrisoquine inhibited 7-ethoxyresorufin deethylation competitively. These results suggest that debrisoquine and 7-ethoxyresorufin may be metabolised by a common P-450 form in human liver. The effect of cytochrome P-450 inducers on the metabolism of the three substrates was also examined in rat liver. Debrisoquine hydroxylation was not enhanced by phenobarbitone, beta-naphthoflavone or isosafrole.

Animals↗