This report describes a model of angiogenesis which develops in admixtures (co-cultures) of human umbilical vein endothelial cells (HUVEC) and human diploid fibroblasts of dermal origin from adult patients. The system does not require the addition of further growth factors other than those normally present in endothelial growth medium (EGM), nor matrix proteins, and cell growth and proliferation are allowed to occur in a standard low (2%) concentration of fetal calf serum. Angiogenesis was specifically stimulated in response to vascular endothelial growth factor (VEGF), resulting in an increased development of structures resembling a microvasculature bed. Alternatively, angiogenesis was inhibited by addition of an excess of neutralising anti-VEGF antibodies, and the anti-angiogenic drugs such as suramin. We briefly show that stimulatory and inhibitory activities can be easily and quickly quantified by image analysis. Tubule formation was confirmed by confocal and electron microscopy, and the development and disposition of these structures within the co-cultures has been analysed immunochemically to show expression of specific endothelial cell determinants, such as PECAM-1. On this and a number of other criteria, the findings validate this in vitro process as a model of in vivo angiogenesis that can be quantified to assay stimulatory and inhibitory agents, signals and drugs.

Background:  With the current obesity epidemic, the search for effective weight loss approaches is required. In the present study, changes in weight, body composition and cardiovascular (CV) risk in response to a low‐fat, reduced‐energy diet (LFRE), a low‐carbohydrate/high‐protein diet (LCHP), or a commercially available very low‐calorie diet (LighterLife; LL) were assessed. Methods:  One hundred and twenty obese patients (body mass index ≥35 kg/m2) underwent a screening period of 3 months on the LFRE. Those who lost >5% of their body weight were maintained on this approach for an additional 3 months, whereas those who lost >10% at this time were maintained for 1 year. Patients failing to achieve these targets were randomly allocated to either the LCHP (n = 38) or LL (n = 34) for a period of 9 months. Results:  Significantly greater weight loss was seen for patients on the LL than the LCHP at 3 (mean (±SD) −11.6 ± 12.9 vs −2.8 ± 4.5 kg, respectively; P < 0.0001) and 9 months (−15.1 ± 21.1 vs −1.9 ± 5.0 kg, respectively; P < 0.0001) after screening. Significantly greater improvement in total cholesterol, low‐density lipoprotein–cholesterol, fasting glucose, and diastolic blood pressure was seen at 3 months in patients on the LL compared with the LCHP (P < 0.05). These differences were no longer significant at 9 months, with the exception of fasting glucose. The attrition rate was elevated in the LCHP group, but did not differ significantly from the LL group. Conclusion:  Greater weight loss and improved CV risk were achieved with the LL, which mostly reflects the patient support provided for each dietary treatment.

Selenium (Se)-containing proteins have important roles in protecting cells from oxidative damage. This work investigated the effects of Se-depletion on the expression of the genes encoding selenoproteins in colonic mucosa from rats fed diets of different Se content and in human intestinal Caco-2 cells grown in Se-adequate or Se-depleted culture medium. Se-depletion produced statistically significant (P < 0.05) falls in glutathione peroxidase (GPX) 1 mRNA (60-83%) and selenoprotein W mRNA (73%) levels, a small but significant fall in GPX4 mRNA (17-25%) but no significant change in GPX2. The data show that SelW expression in the colon is highly sensitive to Se-depletion.

Cigarette smoking and hyperfibrinogenaemia are both significant risk factors for the development of cardiovascular disease. Two studies are described here which aimed to establish the metabolic mechanism responsible for the raised plasma fibrinogen concentration observed in smokers. Chronic smokers had a significantly elevated absolute rate of fibrinogen synthesis (ASR) compared with non-smokers (22.7 +/- 1.3 mg/kg per day versus 16.0 +/- 1.3 mg/kg per day; means +/- S.E.M., P < 0.01), with plasma levels of fibrinogen significantly correlated with fibrinogen synthesis (r = 0.65, P = 0.04). Unlike fibrinogen, plasma albumin concentrations were lower in smokers than in non-smokers (45 +/- 0.4 versus 47 +/- 0.7 g/l, P < 0.05), but there was no difference in rates of albumin synthesis between the two groups. Two weeks cessation from smoking by previously chronic smokers was associated with a rapid and marked fall in plasma fibrinogen concentration (from 3.06 +/- 0.11 g/l to 2.49 +/- 0.14 g/l, P < 0.001), and a significant reduction in ASR (a 33% reduction, from 24.1 +/- 1.7 to 16.1 +/- 1.0 mg/kg per day, P < 0.001). These studies suggest a primary role for increased synthesis in producing the hyperfibrinogenaemia associated with smoking. Moreover, abstention from smoking for a period of only 2 weeks induces a significant decrease in the rate of fibrinogen synthesis by the liver, with a concomitant reduction in the plasma fibrinogen concentration.

Very-low-calorie diets (VLCDs) are used to treat obesity, often in a non-clinical setting, and the typical formulation of a minimum of 50 g carbohydrates daily can induce a mild dietary ketosis. This clinically benign state is sometimes confused with the non-metabolically adapted state of ketoacidosis, and this misunderstanding may lead to the rejection of VLCDs as a suitable obesity treatment. This paper summarises and discusses the difference between physiological ketosis and pathological ketoacidosis, the benefits of ketosis-inducing weight-loss regimen such as VLCDs and why ketoacidosis should never be the diagnosis in a non-type 1 diabetic on a carbohydrate-restricted diet.