PubMed Health⌕ Search

Biomedical subjects

S L Nuttall

Publications and source records attributed to S L Nuttall.

At least 19 recordsLinked to original sources
PubMed2004

Changes in plasma lipids and markers of oxidative stress in normal pregnancy and pregnancies complicated by diabetes.

The purpose of the present study was to determine changes in plasma lipids and markers of oxidative stress longitudinally in pregnancy complicated by diabetes compared with non-diabetic pregnancy. This was carried out by following a group of normal pregnant women (n=17) and groups of pregnant women with Type I diabetes (n=19), Type II diabetes (n=12) and gestational diabetes mellitus (n=12) throughout pregnancy, with sampling carried out at the end of each trimester. Serum total cholesterol and triacylglycerols (triglycerides) were determined using standard colorimetric techniques and low-density lipoprotein (LDL) subfraction profile by disc PAGE. Total antioxidant capacity (TAC) was determined by enhanced chemiluminescence and lipid hydroperoxides by the ferrous oxidation of Xylenol Orange method. Total cholesterol and triacylglycerols increased significantly throughout pregnancy in all groups, but there were no significant differences between normal and diabetic women with respect to either. The LDL score was significantly higher (P<0.001) in diabetic women compared with normal women at each point throughout pregnancy, although there were no significant differences between the diabetic groups. There was evidence of greater oxidative stress in diabetic compared with normal women throughout. Corrected TAC was significantly lower (P<0.001) in all diabetic women throughout pregnancy. In addition, lipid hydroperoxides were higher in all diabetic compared with normal women, particularly so in those with Type II diabetes (P<0.05). These changes may have important implications for diabetic women during pregnancy, as an elevated risk of pre-eclampsia is thought to reflect an oxidative stress-related mechanism. In addition, these changes may have important implications for the development of atherosclerosis and the long-term cardiovascular health of women with diabetes.

Adult↗
PubMed2003

Cardiovascular risk in systemic lupus erythematosus--evidence of increased oxidative stress and dyslipidaemia.

OBJECTIVES: Systemic lupus erythematosus (SLE) is associated with severe and premature cardiovascular disease, which is not explained by traditional risk factors alone. This study aimed to investigate markers of oxidative stress, lipid metabolism and inflammation as potential cardiovascular risk factors in women with SLE. METHODS: Venous blood samples were taken from 53 female Caucasian patients with SLE and from healthy age- and sex-matched controls. Samples were analysed for markers of oxidative stress, lipid metabolism [including low-density lipoprotein (LDL) subfraction profile] and C-reactive protein (CRP). RESULTS: Female SLE patients had an atherogenic lipid profile characterized by raised total cholesterol and triglycerides, and the presence of small, dense LDL subfractions compared with healthy controls. These changes were associated with increased oxidative damage and a moderately raised CRP. CONCLUSIONS: The results provide evidence for free radical and inflammatory activity in SLE and suggest potential targets to reduce the risk of cardiovascular disease in these patients.

Adult↗
PubMed2003

A comparison of the beta1-selectivity of three beta1-selective beta-blockers.

OBJECTIVE: To determine the relative beta1-selectivity of three beta-blockers (nebivolol, bisoprolol and atenolol), administered orally at normal therapeutic doses, by assessing their impact on the beta2-mediated, haemodynamic and biochemical responses to a terbutaline infusion, which decreases serum potassium and increases serum glucose and insulin. METHODS: Twenty-four healthy volunteers (14 men, 10 women), with no history of respiratory disease, attended on five separate occasions; beta-blockers (nebivolol 5 mg, bisoprolol 10 mg, atenolol 50 and 100 mg) or placebo were supplied in random order. Three baseline blood samples were collected at 65-85 min post-beta-blocker. A 60-min terbutaline infusion was started 90 min after taking the beta-blocker. Blood samples were taken and blood pressure and heart rate recorded at 15 min intervals up to 30-min post-infusion. Blood samples were analysed for serum potassium, glucose and insulin concentrations. RESULTS: Terbutaline increased heart rate. Pretreatment with nebivolol caused a modest and non-significant reduction in terbutaline-induced tachycardia whilst bisoprolol produced a more marked effect. Atenolol at both 50 and 100 mg doses caused a highly significant reduction in terbutaline-induced tachycardia. All active preparations had a comparable impact on the terbutaline-induced increase in systolic blood pressure, but the drugs had no impact on the changes produced in diastolic blood pressure. After pretreatment with placebo, the terbutaline infusion caused a significant decrease in serum potassium and increases in serum glucose and insulin. Pretreatment with nebivolol had no discernible effect on potassium compared with placebo. In contrast, when compared with either placebo or nebivolol, bisoprolol (P < 0.01) and both doses of atenolol (P < 0.001) significantly attenuated the hypokalaemic effect of terbutaline. Treatment with nebivolol and bisoprolol modestly but significantly reduced the terbutaline-induced increases in glucose (P < 0.05). The blocking effects of both doses of atenolol were highly significant (P < 0.001) when compared with placebo and also significant (P < 0.05 and P < 0.01, respectively) when compared with nebivolol and bisoprolol. A similar pattern of responses with the different beta-blocker treatments was observed for the effects on insulin concentrations during the terbutaline infusion. CONCLUSION: The beta1-selectivity of three different beta1-blockers has been demonstrated in healthy volunteers using the blocking of biochemical and haemodynamic responses to a beta2 stimulus. Terbutaline alone caused an increase in heart rate, a rise in systolic blood pressure, a fall in serum potassium and a rise in both serum glucose and insulin. In this study, for both haemodynamic and biochemical responses, atenolol 100 mg had the greatest beta2-blocking effect, nebivolol 5 mg the least. Bisoprolol 10 mg and atenolol 50 mg had intermediate effects; bisoprolol was the more beta1-selective of these two.

Administration, Oral↗
PubMed2003

Insulin resistance--the new goal!

Diabetes mellitus is a well-recognized risk-factor for coronary artery disease (CAD). Epidemiological studies have shown that the risk of CAD increases two to sixfold in patients with type 2 diabetes compared with those without the disease. Furthermore the prevalence of diabetes in the UK has increased by 30% since 1991 and the world population of people with diabetes in 2010 is expected to be twice that of 1990. In addition whilst the mortality from CAD in patients without diabetes has declined over the past 20 years the mortality in men with type 2 diabetes has not changed and in women may have increased. UKPDS and other studies have shown a significant improvement in the onset and course of microvascular complications with good diabetic control. However the same is not true for macrovascular complications for which there is no good evidence of improvement with better diabetic control. This apparent lack of benefit from improved care of diabetic patients has led to many different approaches. These include attempts to achieve even better glycaemic control, greater emphasis on other risk factors particularly hypertension and interestingly attention to the prediabetic state characterized by insulin resistance (IR). The latter is associated with a number of abnormalities which could play a causative role in the development of cardiovascular disease. This article will review the concept of IR and the possible interventions available to tackle it.

Cardiovascular Diseases↗
PubMed2003

The impact of therapeutic doses of paracetamol on serum total antioxidant capacity.

INTRODUCTION: A link between regular paracetamol intake and asthma in adults has recently been postulated. Detoxification of paracetamol may deplete stores of glutathione, which is one of the major antioxidants present in the lung. A reduced source of glutathione in the lung may lead to increased oxidative damage to the epithelium and hence increased frequency and severity of asthma attacks in susceptible individuals. AIM OF STUDY: This study aimed to determine whether regular intake of maximum therapeutic doses of paracetamol reduced serum antioxidant capacity in healthy volunteers. METHODS: Fifteen young healthy volunteers (nine men, six women, mean age 21.3 years, range 19-32) took maximum therapeutic doses of paracetamol (1 g four times a day) for 14 days. On days 0 and 14 blood samples were taken at baseline and hourly for a period of 4 h following ingestion of 1 g paracetamol. Single venous blood samples were collected 1 h after ingestion of 1 g paracetamol on days 4, 7 and 10. Blood samples were analysed for serum paracetamol concentration and total antioxidant capacity. RESULTS: Mean total antioxidant capacity was significantly reduced over the 3-h post-dosing on both days 0 and 14 (P < 0.01). The results from days 4, 7 and 10 showed a trend towards reduced antioxidant activity over time. On day 14 values were consistently lower compared with the corresponding times on day 0 (P < 0.01 at 0, 1, 3 and 4 h, P < 0.05 at 2 h). CONCLUSIONS: Chronic ingestion of maximum therapeutic doses of paracetamol depletes serum antioxidant capacity in healthy volunteers in as few as 14 days, possibly by a reduction in glutathione. This may have implications for analgesic use in asthmatic individuals. Further studies are now required to assess the impact of paracetamol on antioxidant defences in the lung.

Acetaminophen↗
PubMed2002

Oxidative stress in malignant and non-malignant phase hypertension.

Malignant hypertension (MHT) is a rare and severe form of hypertension characterised by arteriolar necrosis and severe vascular damage, leading to stroke, myocardial infarction and death. We hypothesised that in addition to endothelial damage, MHT may be associated with increased oxidative stress. Lipid hydroperoxides (LHP, an index of oxidative damage) and plasma von Willebrand factor (vWf, an index of endothelial damage/dysfunction) were measured in 16 patients with MHT and compared with 16 non-malignant essential hypertensives and 32 normotensive controls. vWf was greater in MHT (mean 117 iU/dL) than in non-malignant hypertensives (97 iU/dL) or normotensive controls (100 iU/dL) (ANOVA P = 0.017). However, although LHP were greater in MHT (mean 10.6 micromol/L) than in normotensives (4.5 micromol/L, P < 0.001), the levels in MHT were similar to those in non-malignant hypertension (12.3 micromol/L). In conclusion endothelial damage (raised vWf) was more evident in MHT compared with both normotensive controls and with non-malignant hypertension, whilst oxidative stress (raised LHP) was increased to a similar extent in both hypertension groups when compared with normotensive controls. These observations raise the possibility abnormal oxidative stress is probably not the mechanism responsible for the endothelial damage seen in malignant phase hypertension.

Analysis of Variance↗
PubMed2002

Oxidative stress and normal pregnancy.

OBJECTIVE: To determine whether, in normal pregnancies, there is evidence of oxidative stress that is related to the lipid changes observed in pregnancy. DESIGN: Longitudinal study of healthy women having a normal pregnancy. Samples were obtained towards the end of each trimester and after 8 weeks postpartum. PATIENTS: Seventeen healthy women during a normal singleton pregnancy were compared with 12 healthy, non-pregnant women. MEASUREMENTS: Oxidative stress was determined by measuring total antioxidant capacity (TAC), uric acid and lipid hydroperoxides (LHP). Lipid status was evaluated by measuring total and high-density lipoprotein cholesterol, triglycerides and low-density lipoprotein (LDL) subfractions. RESULTS: Pregnancy was associated with decreased TAC and uric acid in the first trimester, which gradually increased during pregnancy, reaching normal values during the postpartum period. LHP significantly increased towards the end of pregnancy. The changes observed in LHP were significantly correlated with increases in LDL subfraction profile. CONCLUSIONS: Late pregnancy was associated with the formation of susceptible, oxidisable particles (high LDL score) and an increase in oxidative damage. These biochemical changes may be relevant for the long-term cardiovascular health of women, especially those of high parity or those who are at high risk for cardiovascular disease (e.g. women with diabetes).

Adult↗
PubMed2002

Adjuvant treatment of patients with antineutrophil cytoplasmic antibody-associated vasculitis with vitamins E and C reduces superoxide production by neutrophils.

OBJECTIVES: Neutrophils when activated generate a respiratory burst which has been implicated in the pathogenesis of primary systemic vasculitis. Neutrophils from patients with vasculitis have a greater respiratory burst than normal healthy donors. The aim of this study was to assess the effects of antioxidant treatment (vitamins E and C) on the generation of a respiratory burst from neutrophils isolated from patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. METHODS: Neutrophils were isolated from patients with systemic vasculitis and healthy donors. Spontaneous superoxide generation was measured by the reduction of ferricytochrome c. The patients were treated with antioxidants, vitamins E and C, and spontaneous superoxide generation, vitamin C and total antioxidant capacity were measured before and after treatment. RESULTS: The treatment of the patients with antioxidants resulted in a reduction in spontaneous superoxide generation (pre-treatment 8.41+/-0.7 nmol/10(6) cells; post-treatment 5.64+/-0.6 nmol/10(6) cells; P<0.05). There was no significant difference in the superoxide generation from normal controls who did not receive treatment, measured prior to commencement of the study and 10 days later (first reading 4.81+/-0.5 nmol/10(6) cells; second reading 5.32+/-0.4 nmol/10(6) cells; P>0.05). Total antioxidant capacity increased significantly following treatment with vitamins C and E (555.4+/-142 vs. 668.6+/-186 micromol/l trolox equivalent; P=0.01) as did vitamin C concentrations (56.5+/-27 vs. 137.7+/-64 micromol/l; P=0.002). CONCLUSIONS: In this preliminary study, the treatment of patients with antioxidants, vitamins E and C, reduced neutrophil generation of superoxide and suggests that antioxidants may have an important role as adjuvant therapy. The evidence presented should form the basis of a larger randomized placebo-controlled trial of vitamins E and C as adjuvant therapy in patients with ANCA-associated systemic vasculitis.

Adult↗