Gwen Kennedy

Dark chocolate inhibits platelet aggregation in healthy volunteers

Cardiovascular disease is a leading cause of death in the UK. The flavonoids found in cocoa may produce a cardio-protective role for chocolate with a high cocoa content. Thirty healthy volunteers were randomised to receive 100 g of white, milk or dark chocolate, and assessments of platelet function were undertaken on venous blood samples before and after chocolate consumption. White and milk chocolate had no significant effect on platelets. However dark chocolate inhibited collagen-induced platelet aggregation in platelet rich plasma. In the future dark chocolate may have a role in prevention of cardiovascular and thromboembolic diseases.

Abnormal markers of endothelial cell activation and oxidative stress in children, adolescents and young adults with type 1 diabetes with no clinical vascular disease.

Endothelial cell dysfunction is an early feature of vascular disease and oxidative stress may be involved in its pathogenesis.

Increased neutrophil apoptosis in chronic fatigue syndrome

Background/Aims: Many patients with chronic fatigue syndrome (CFS) have symptoms that are consistent with an underlying viral or toxic illness. Because increased neutrophil apoptosis occurs in patients with infection, this study examined whether this phenomenon also occurs in patients with CFS. Methods: Apoptosis was assessed in patients with CFS in conjunction with concentrations of the anti-inflammatory cytokine, transforming growth factor β1 (TGFβ1). Results: The 47 patients with CFS had higher numbers of apoptotic neutrophils, lower numbers of viable neutrophils, increased annexin V binding, and increased expression of the death receptor, tumour necrosis factor receptor-I, on their neutrophils than did the 34 healthy controls. Patients with CFS also had raised concentrations of active TGFβ1 (p < 0.005). Conclusions: These findings provide new evidence that patients with CFS have an underlying detectable abnormality in their immune cells.

Low-grade inflammation and arterial wave reflection in patients with chronic fatigue syndrome

Some of the symptoms reported by people with CFS (chronic fatigue syndrome) are associated with various cardiovascular phenomena. Markers of cardiovascular risk, including inflammation and oxidative stress, have been demonstrated in some patients with CFS, but little is known about the relationship between these and prognostic indicators of cardiovascular risk in this patient group. In the present study, we investigated the relationship between inflammation and oxidative stress and augmentation index, a measure of arterial stiffness, in 41 well-characterized patients with CFS and in 30 healthy subjects. AIx@75 (augmentation index normalized for a heart rate of 75 beats/min) was significantly greater in patients with CFS than in control subjects (22.5+/-1.7 compared with 13.3+/-2.3% respectively; P=0.002). Patients with CFS also had significantly increased levels of CRP (C-reactive protein) (2.58+/-2.91 compared with 1.07+/-2.16 mug/ml respectively; P<0.01) and 8-iso-prostaglandin F(2alpha) isoprostanes (470.7+/-250.9 compared with 331.1+/-97.6 pg/ml respectively; P<0.005). In patients with CFS, AIx@75 correlated significantly with logCRP (r=0.507, P=0.001), isoprostanes (r=0.366, P=0.026), oxidized LDL (low-density lipoprotein) (r=0.333, P=0.039) and systolic blood pressure (r=0.371, P=0.017). In a stepwise multiple regression model, including systolic and diastolic blood pressure, body mass index, CRP, tumour necrosis factor-alpha, interleukin-1, oxidized LDL, high-density lipoprotein-cholesterol levels, isoprostanes, age and gender, AIx@75 was independently associated with logCRP (beta=0.385, P=0.006), age (beta=0.363, P=0.022) and female gender (beta=0.302, P=0.03) in patients with CFS. The combination of increased arterial wave reflection, inflammation and oxidative stress may result in an increased risk of future cardiovascular events. Assessment of arterial wave reflection might be useful for determining cardiovascular risk in this patient group.

Lowering of oxidative stress improves endothelial function in healthy subjects with habitually low intake of fruit and vegetables: A randomized controlled trial of antioxidant- and polyphenol-rich blackcurrant juice

Inadequate intake of the recommended five-a-day fruit and vegetable portions might contribute to increased cardiovascular disease risk. We assessed the effects of dietary intake of a blackcurrant juice drink, rich in vitamin C and polyphenols, on oxidative stress and vascular function. This was a double-blind, placebo-controlled, parallel group study of 66 healthy adults who habitually consume <2 portions of fruit and vegetables per day. Participants were randomly allocated to consume 250ml of placebo (flavored water) or low or high blackcurrant juice drink four times a day for 6 weeks. Flow-mediated dilation (FMD) and plasma concentrations of F2-isoprostanes and vitamin C were measured. In the high blackcurrant juice drink group FMD increased significantly (5.8±3.1 to 6.9±3.1%, P=0.022) compared with the placebo group (6.0±2.2 to 5.1±2.4%). Plasma vitamin C concentration increased significantly in the low (38.6±17.6 to 49.4±21.0µmol/L, P<0.001) and high (34.6±20.4 to 73.8±23.3µmol/L, P<0.001) blackcurrant juice drink groups compared with the placebo group (38.1±21.0 to 29.0±17.6µmol/L). F2-isoprostane concentrations were significantly lower in the high blackcurrant juice drink group (225±64pg/ml) compared with the low blackcurrant juice drink (257±69pg/ml, P=0.002) and placebo group (254±59pg/ml, P=0.003). At follow-up, changes in plasma vitamin C correlated significantly with changes in FMD (r=0.308, P=0.044). Consumption of blackcurrant juice drink high in vitamin C and polyphenols can decrease oxidative stress and improve vascular health in individuals with habitually low dietary fruit and vegetable intake.

Plasma IL‐6, its soluble receptors and F2‐isoprostanes at rest and during exercise in chronic fatigue syndrome

The aim of the current study was to investigate the levels of interleukin‐6 (IL‐6), its soluble receptors (sIL‐6R and sgp130) and F2‐isoprostanes, at rest and during exercise, in patients with chronic fatigue syndrome (CFS). Six male CFS patients and six healthy controls performed an incremental exercise test to exhaustion and a submaximal exercise bout to exhaustion. Blood samples taken in the submaximal test at rest, immediately post‐exercise and 24 h post‐exercise were analyzed for IL‐6, sIL‐6R, sgp130 and F2‐isoprostanes. A further 33 CFS and 33 healthy control participants gave a resting blood sample for IL‐6 and sIL‐6R measurement. During the incremental exercise test only power output at the lactate threshold was lower (P<0.05) in the CFS group. F2‐isoprostanes were higher (P<0.05) in CFS patients at rest and this difference persisted immediately and 24 h post‐exercise. The exercise study found no differences in IL‐6, sIL‐6R or sgp130 at any time point between groups. In the larger resting group, there were no differences in IL‐6 and sIL‐6R between CFS and control groups. This investigation has demonstrated that patients with CFS do not have altered plasma levels of IL‐6, sIL‐6R or sgp130 either at rest or following exercise. F2‐isoprostanes, however, were consistently higher in CFS patients.

Glycaemic control and plasma lipoproteins in menopausal women with Type 2 diabetes treated with oral and transdermal combined hormone replacement therapy

Abstract Aims: To compare the effect of a fixed combination of an oestrogen (17-β oestradiol) with a cyclical progestagen (norethisterone) on glycaemic control, plasma lipoproteins and haemostatic factors in women with Type 2 diabetes. Methods: Oral and transdermal hormone replacement therapy (HRT) were compared to no HRT treatment in 33 postmenopausal women with Type 2 diabetes, in a 12-week randomised prospective open parallel group study. Results: In the 11 women who received 12 weeks of oral HRT, there was a significant fall in total cholesterol (5.9±1.0 (S.D.) to 4.7±1.0 mmol l −1 , P =0.005), low density lipoprotein cholesterol (3.44±0.89 to 2.77±0.92 mmol l −1 , P =0.005) and triglyceride values (median (range)), (2.46 (0.96–5.52) to 2.29 (1.00–3.87) mmol l −1 , P 1c ) (7.4±1.4 to 6.8±1.2%, P ⩽0.005). Oral HRT additionally reduced the cell adhesion factor E-selectin (82±33 to 60±20 μg l −1 , P P −1 , P Conclusion: In women with Type 2 diabetes, cyclical oestrogen and progestagen taken orally for 12 weeks significantly improved glycaemic control and lipoprotein concentrations. These metabolic benefits were not apparent when a similar HRT preparation was administered transdermally.

Biochemical and Vascular Aspects of Pediatric Chronic Fatigue Syndrome

OBJECTIVE To evaluate the biochemical and vascular aspects of pediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). DESIGN Cross-sectional clinical study. SETTING Tayside, Scotland, United Kingdom. PARTICIPANTS Twenty-five children with CFS/ME and 23 healthy children recruited from throughout the United Kingdom. INTERVENTIONS Participants underwent a full clinical examination to establish a diagnosis of CFS/ME and were asked to describe and score their CFS/ME symptoms. Biochemical markers were measured. Arterial wave reflection was estimated to assess systemic arterial stiffness. MAIN OUTCOME MEASURES Markers of oxidative stress and free radicals, C-reactive protein level, white blood cell apoptosis, and arterial wave reflection. RESULTS Children with CFS/ME had increased oxidative stress compared with control individuals (isoprostanes: 252.30 vs 215.60 pg/mL, P = .007; vitamin C, mean [SD]: 0.84 [0.26] vs 1.15 [0.28] mg/dL, P < .001; vitamin E, 8.72 [2.39] vs 10.94 [3.46] microg/mL, P = .01) and increased white blood cell apoptosis (neutrophils: 53.7% vs 35.7%, P = .005; lymphocytes: 40.1% vs 24.6%, P = .009). Arterial stiffness variables did not differ significantly between groups (mean augmentation index, -0.57% vs -0.47%, P = .09); however, the derived variables significantly correlated with total (r = 0.543, P = .02) and low-density lipoprotein (r = 0.631, P = .004) cholesterol in patients with CFS/ME but not in controls. CONCLUSIONS Biomedical anomalies seen in adults with CFS/ME-increased oxidative stress and increased white blood cell apoptosis-can also be observed in children with clinically diagnosed CFS/ME compared with matched controls. Unlike in their adult counterparts, however, arterial stiffness remained within the reference range in these pediatric patients.

Peripheral cholinergic function in humans with chronic fatigue syndrome, Gulf War syndrome and with illness following organophosphate exposure

In the present study, we have investigated whether the peripheral cholinergic abnormalities that we have reported previously [Spence, Khan and Belch (2000) Am. J. Med. 108, 736-739] in patients with chronic fatigue syndrome (CFS) are also present in those with Gulf War syndrome (GWS) and agricultural workers exposed to organophosphate pesticides, where cholinesterase inhibition is specifically implicated. We also looked at whether these abnormalities might be due to a reduction in the activity of cholinesterase expressed on the vascular endothelium. We used laser Doppler imaging to measure the forearm skin blood flow responses to iontophoresis of acetylcholine and of methacholine (which is resistant to breakdown by cholinesterase) in patients with CFS, GWS and those with a history of ill health after definite organophosphate exposure, as well as in matched healthy controls. The response to acetylcholine was significantly higher in patients with CFS than in controls ( P =0.029, repeated-measures ANOVA), but was normal in those with GWS and those exposed to organophosphates. The methacholine response was higher than the acetylcholine response in all patient groups except for those with CFS, where there was no difference between the responses. Although there are many clinical similarities between these three illnesses, our results indicate peripheral cholinergic abnormalities in the vascular endothelium of only patients with CFS, suggesting that this syndrome has a different aetiology, which might involve inhibition of vascular cholinesterase.

Effect of intermittent vitamin D3 on vascular function and symptoms in chronic fatigue syndrome – A randomised controlled trial

BACKGROUND AND AIMS Low 25-hydroxyvitamin D levels are common in patients with chronic fatigue syndrome; such patients also manifest impaired vascular health. We tested whether high-dose intermittent oral vitamin D therapy improved markers of vascular health and fatigue in patients with chronic fatigue syndrome. METHODS AND RESULTS Parallel-group, double-blind, randomised placebo-controlled trial. Patients with chronic fatigue syndrome according to the Fukuda (1994) and Canadian (2003) criteria were randomised to receive 100,000 units oral vitamin D3 or matching placebo every 2 months for 6 months. The primary outcome was arterial stiffness measured using carotid-femoral pulse wave velocity at 6 months. Secondary outcomes included flow-mediated dilatation of the brachial artery, blood pressure, cholesterol, insulin resistance, markers of inflammation and oxidative stress, and the Piper Fatigue scale. As many as 50 participants were randomised; mean age 49 (SD 13) years, mean baseline pulse wave velocity 7.8 m/s (SD 2.3), mean baseline office blood pressure 128/78 (18/12) mmHg and mean baseline 25-hydroxyvitamin D level 46 (18) nmol/L. 25-hydroxyvitamin D levels increased by 22 nmol/L at 6 months in the treatment group relative to placebo. There was no effect of treatment on pulse wave velocity at 6 months (adjusted treatment effect 0.0 m/s; 95% CI -0.6 to 0.6; p = 0.93). No improvement was seen in other vascular and metabolic outcomes, or in the Piper Fatigue scale at 6 months (adjusted treatment effect 0.2 points; 95% CI -0.8 to 1.2; p = 0.73). CONCLUSION High-dose oral vitamin D3 did not improve markers of vascular health or fatigue in patients with chronic fatigue syndrome. TRIAL REGISTRATION www.controlled-trials.com, ISRCTN59927814.