Glucose challenge stimulates reactive oxygen species (ROS) generation by leucocytes

Diabetes mellitus is associated with increased ROS generation, oxidative injury and obesity. To elucidate the relationship between nutrition and ROS generation, we have investigated the effect of glucose challenge on ROS generation by leucocytes, p47phox protein, a key protein in the enzyme NADPH oxidase and alpha-tocopherol levels. Blood samples were drawn from 14 normal subjects prior to, at 1, 2 and 3 h following ingestion of 75 g glucose. ROS generation by polymorphonuclear leucocytes (PMNL) and mononuclear cells (MNC) increased to a peak of 244 +/- 42% and 233 +/- 34% of the basal respectively at 2h. The levels of p47phox in MNC homogenates increased significantly at 2 h and 3 h after glucose intake. alpha-Tocopherol levels decreased significantly at 1 h, 2 h and 3 h. We conclude that glucose intake stimulates ROS generation and p417phox of NADPH oxidase; increases oxidative load and causes a fall in alpha-tocopherol concentration.     

Computer-based detection of neonatal changes to branching morphogenesis reveals different mechanisms of and predicts prostate enlargement in mice haplo-insufficient for bone morphogenetic protein 4

Early changes to branching morphogenesis of the prostate are believed to lead to enlargement of the gland in adult life. However, it has not been possible to demonstrate directly that alterations to branching during the developmental period have a permanent effect on adult prostate size. In order to examine branching morphogenesis in a quantitative manner in neonatal mice, a combination of imaging and computational technology was used to detect and quantify branching using bone morphogenetic protein 4 haplo-insufficient mice that develop enlarged prostate glands in adulthood. Accurate estimates were made of six parameters of branching, including prostate ductal length and volume and number of main ducts, branches, branch points, and tips. The results show that the prostate is significantly larger on day 3, well before the emergence of the phenotype in older animals. The ventral prostate is enlarged because the number of main epithelial ducts is increased; enlargement of the anterior prostate in mutant animals occurs because there are more branches. These lobe-specific mechanisms underlying prostate enlargement indicate the complex nature of gland pathology in mice, rather than a simple increase in weight or volume. This method provides a powerful means to investigate the aetiology of prostate disease in animal models prior to emergence of a phenotype in later life.     

Angiotensin II receptor blocker valsartan suppresses reactive oxygen species generation in leukocytes,nuclear factor-kappa B,in mononuclear cells of normal subjects: evidence of an antiinflammatory action

In view of the pro-oxidant and proinflammatory effects of angiotensin II, we have tested the hypothesis that valsartan, an angiotensin receptor blocker, may exert a suppressive action on reactive oxygen species (ROS) generation, nuclear factor kappa B (NF-kappa B) in mononuclear cells. Four groups of eight normal subjects were given 1) 160 mg daily of valsartan, 2) 80 mg daily of simvastatin, 3) 40 mg quinapril, or 4) no treatment. Fasting blood samples were obtained before treatment and at d 1, 8, and 14 (7 d after the cessation of the drug). After valsartan, ROS generation by polymorphonuclear cells and mononuclear cells fell significantly by more than 40% (P < 0.01). NF-kappa B binding activity and the expression of total cellular p65, a protein component of NF-kappa B, fell significantly (P < 0.01). The expression of inhibitor kappa B (I kappa B) increased significantly (P < 0.05). Plasma C-reactive protein (CRP) concentration fell significantly (P < 0.01). All indices, except I kappa B, reverted toward baseline, 7 d after the cessation of the drug. I kappa B persisted in an elevated state. Neither quinapril nor simvastatin given for 7 d produced a suppression of ROS generation, intranuclear NF-kappa B, p65, or CRP, and these two agents did not alter cellular I kappa B either. The untreated controls also did not demonstrate a change in their ROS generation or NF-kappa B binding activity or plasma CRP concentration. We conclude that valsartan at a modest dose exerts a profound and rapid ROS and inflammation-suppressive effect that may be relevant to its potential beneficial effects in atherosclerosis, diabetes, and congestive cardiac failure. In contrast, quinapril and simvastatin produced no similar effect over the period of 1 wk. Our observations may also have implications to clinical situations in which a rapid antiinflammatory effect is required.     

Nadolol inhibits reactive oxygen species generation by leukocytes and linoleic acid oxidation

We studied the effect of short-term nadolol administration on the reactive oxygen species (ROS) generation by polymorphonuclear leukocytes and mononuclear cells in 8 normal subjects. At a oral dose of 40 mg/day for 5 days, nadolol produced a decrease in the ROS generation by leukocytes. ROS generation by polymorphonuclear leukocytes decreased by 38% from 134 +/- 44 mV at baseline to 83 +/- 34 mV after 5 days (p = 0.005), and ROS generation by mononuclear cells decreased by 33% from 174 +/- 69 mV at baseline to 117 +/- 55 mV after 5 days (p = 0.015). There was also a significant reduction in linoleic acid oxidation as reflected by the lower levels of 9- and 13- hydroxy-octadecadienoic acid after 5 days. There was no change in the plasma thiobarbituric acid-reacting substances, a less sensitive index of oxidative damage to lipids. There was also no significant change in the levels of metatyrosine and orthotyrosine, which are known indexes of oxidative damage to amino acids and proteins. The absence of a significant change in metatyrosine, orthotyrosine, and thiobarbituric acid-reacting substances may reflect the short duration of nadolol administration and the decreased ROS load. Because ROS may induce lipid peroxidation, this inhibitory effect of nadolol on ROS generation by leukocytes and linoleic acid oxidation may inhibit low-density lipoprotein oxidation and thus atherogenesis. This effect may partly explain the favorable outcomes observed in patients with coronary artery disease on long-term beta-blocker therapy.     

High prevalence of metabolic syndrome among Kuwaiti adults--a wake-up call for public health intervention

The socio-economic development which followed the discovery of oil resources brought about considerable changes in the food habits and lifestyle of the Kuwaiti population. Excessive caloric intake and decreased energy expenditure due to a sedentary lifestyle have led to a rapid increase in obesity, diabetes and other non-communicable chronic diseases in the population. In this paper, we examine the prevalence of the Metabolic Syndrome (MetS) among Kuwaiti adults (≥20 years) using data from the first national nutrition survey conducted between July 2008 and November 2009. The prevalence of MetS was 37.7% in females and 34.2% in males by NCEP criteria, whereas the values were 40.1% in females and 41.7% in males according to IDF criteria. Prevalence of MetS increased with age and was higher in females than males. The high prevalence of the MetS in Kuwaiti adults warrants urgent public health measures to prevent morbidity and mortality due to cardiovascular complications in the future.     

Caries prediction model in pre-school children in Riyadh, Saudi Arabia

Objectives. To evaluate the significance of variables such as oral hygiene, dietary habits, socio-economic status and medical history of a child in assessing the level of caries risk and to generate a caries prediction model for pre-school Saudi children. Design. Cross-sectional study of pre-school children. Setting. Clinics and schools in Riyadh, Saudi Arabia. Sample and methods. A sample of 446 Saudi pre-school children, 199 males and 247 females, with a mean age of 4·13 years, were selected at random from clinics and schools. Selection was limited to subjects who either had no caries (dmft= 0) or who had high caries experience (dmft > 8). Each child was examined for caries experience and oral hygiene status. Their mothers were interviewed through a standardized questionnaire for information about oral hygiene habits of the children, diet history, childhood illness and socio-economic status. Results. There was a highly significant difference between the two groups in: debris index (P<0.0001), age child started tooth brushing, (P<0·0001), age breastfeeding was stopped (P<0·005), nocturnal bottle feeding with milk formula (P<0·0001), use of sweetened milk (P<0·0001), frequency of use of soft drinks (P<0·0005), frequency of consumption of sweets (P<0·0001), and age at first dental visit (P<0·0001). A caries prediction model developed through stepwise multivariate Logistic Regression (LR) analyses showed debris index, use of sweetened milk in bottle, frequency of consumption of soft drinks, frequency of intake of sweets and child’s age at the first dental visit to be significant. Predictive probability of the model was 86·31% with a sensitivity of 90·1% and a specificity of 80·6%. Conclusions. Risk factors for dental caries have been identified and a caries prediction model has been developed for Saudi pre–school children. The prediction model, if verified, may provide dentists with guidance in identifying high caries risk Saudi pre-school children as targets for preventive programmes