Effect of postprandial hyperglycaemia on blood viscosity in aged patients suffering from type 2 diabetes as compared with healthy volunteers.

Postprandial hyperglycaemia is an independent predictor of cardiovascular risk. Increased blood viscosity has been considered a major cardiovascular risk factor and may play a role in the vascular complications of diabetes. The present study aimed to verify whether blood viscosity is altered by the increased postprandial hyperglycaemia in aged type 2 diabetic patients. The whole blood viscosity, haematocrit, fibrinogen, glucose, insulin, total cholesterol, and triglyceride plasma levels, heart rate, and systolic and diastolic blood pressures were measured in 15 aged patients affected by type 2 diabetes and 15 healthy age-matched individuals before and 60 and 120 min after a test meal (670 kcal energy intake). In the basal condition, in both healthy control individuals and diabetic patients, the whole blood viscosity at higher shear rate (450/s) was significantly correlated in a negative way with the index of insulin resistance (P < 0.05), and in a positive way with the haematocrit value (P < 0.05) and the platelet count (P < 0.01). After the test meal, the whole blood viscosity significantly decreased (P < 0.01 or less) in aged healthy individuals, whereas it remained unchanged in type 2 diabetic patients. In conclusion, the negative action of postprandial hyperglycaemia in diabetes does not occur via a measurable increase of blood viscosity during that period. The decrease of blood viscosity observed during the postprandial period in normal individuals, however, points to the occurrence of alterations in the regulation of the haemorheological equilibrium in the postprandial period in aged type 2 diabetic patients.

Decreased hemoglobin levels are associated with higher plasma level of fibrinogen, irrespective of age.

BACKGROUND: Increased plasma levels of fibrinogen are been associated with an increased risk of cardiovascular accident. We aimed at verifying whether the changes of fibrinogen levels are associated with red blood cell (and/or hemoglobin) concentration. METHODS: A group of 381 carefully selected healthy volunteers (219 male and 162 female), aged from 18 to 101 years, were enrolled in this study. Fasting blood samples were taken and all measurements (fibrinogen plasma level, whole blood viscosity, hemoglobin concentration, hematocrit value, red blood cell and white blood cell count, platelet count, glucose, total cholesterol and triglycerides plasma concentration, and C-reactive protein level) were obtained with standardized methodology using appropriate equipment, procedures, and controls. RESULTS AND CONCLUSIONS: In the male but not in the female group, plasma fibrinogen concentration inversely correlated with hemoglobin (P < 0.0001) and hematocrit value (P < 0.01). In a post hoc analysis, plasma fibrinogen level inversely correlated with hemoglobin in the subgroup of the 93 premenopausal women and directly correlated with age and inversely correlated with platelet count in the subgroup of the 69 postmenopausal women. Results of multiple regression analysis revealed that in all the subjects, except in the postmenopausal women, hemoglobin level is an independent predictor of fibrinogen plasma level. Considering the physiopathologic role of increased plasma fibrinogen concentration and the scarcity of pharmacologic approaches to decrease its level, these findings could be important in designing a preventive therapy of cardiovascular disease.

Ozonized autohemotransfusion does not affect arterial vasodilation in patients with peripheral arterial disease.

Ozonized autohemotransfusion has been used as a complementary therapy in patients with peripheral arterial disease (PAD). To determine whether ozone therapy could acutely modify artery vasodilatory capacity, a flow-mediated dilation test was performed at the brachial artery level before and after an ozonized autohemotransfusion in 16 patients with PAD, mean (± SD) age 55±1.8 years, and 14 healthy volunteers matched for age, sex and body mass index. Before ozonized autohemotransfusion, the mean baseline diameter of the brachial artery was higher in PAD patients than in healthy subjects (4.6±0.54 mm versus 3.6±0.54 mm, P<0.001) while mean flow-mediated brachial artery dilation and percentage of increase in flow were significantly lower in PAD patients than in controls (6.3±6.1% versus 11.8±2.4%, P<0.02; 433±61% versus 580±46%, P<0.02, respectively). No significant changes were observed after ozonized autohemotransfusion, indicating that ozonized autohemotransfusion does not modify endothelium-dependent ischemia-induced vascular reactivity.

Vigorous exercise acutely changes platelet and B-lymphocyte CD39 expression.

CD39/ATP diphosphohydrolase is expressed on B lymphocytes, cytotoxic T lymphocytes, monocytes, platelets, and endothelial cells, and it has a critical role in the inhibition of platelet responsiveness. To determine whether strenuous exercise could acutely change expression of CD39 in platelets and lymphocytes, eight healthy sedentary men, 34 yr old (SD 7), and eight physically active men, 34 yr old (SD 6), performed graded upright cycle ergometry to volitional exhaustion. Blood samples collected both at baseline and after exercise test were employed to measure CD39 expression in platelets and lymphocytes. The percentage of circulating platelet-platelet aggregates, the "in vitro" ADP and collagen-induced platelet aggregation, and the expression of both platelet glycoprotein IIb-IIIa (PAC-1) and P-selectin (CD62) were also considered markers of platelet activation. After strenuous exercise, all subjects demonstrated significant platelet activation as judged by the increased percentage of platelet-platelet aggregates. The in vitro ADP-induced platelet aggregation and the expression of CD62P on ADP-stimulated platelets significantly increased in sedentary but not in active subjects. After exercise, all of the subjects showed a significant reduction of CD39 expression in platelet [sedentary: from 2.2 (SD 0.8) to 1.1% (SD 0.8), P = 0.008; active: from 0.6 (SD 0.2) to 0.35% (SD 0.1), P = 0.009] and an increase of CD39 expression in B lymphocytes [sedentary: from 47 (SD 13) to 60% (SD 11), P = 0.0039; active: from 46 (SD 11) to 59% (SD 11), P = 0.0038]. Taken together, these findings confirm the critical role of this ADPase in inhibition of platelet responsiveness, also suggesting a possible role of B lymphocytes in thromboregulation mechanism.

Acute hyperglycemia alters von Willebrand factor but not the fibrinolytic system in elderly subjects with normal or impaired glucose tolerance.

To assess whether acute hyperglycemia affects fibrinolytic balance in elderly subjects with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT), 40 non-obese elderly subjects (20 NGT, age 68 +/- 8 years; and 20 IGT, age 69 +/- 11 years) were studied. On two experimental days, randomly allocated and spaced 1 week apart, plasma concentrations of glucose, insulin, fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor type 1 and von Willebrand factor (vWF) were measured in each subject at baseline (0) and 30, 60, 90, 120 min after the ingestion of 75 g glucose or a similarly sweet dose of aspartame (250 mg) (control test). In both NGT and IGT elderly subjects, tissue plasminogen activator, plasminogen activator inhibitor type 1 and fibrinogen plasma levels did not significantly change after both oral aspartame and glucose load. In IGT subjects, vWF plasmatic levels decreased after glucose (not aspartame) oral load, reaching the minimum level at 90 min after load (82.7 +/- 7.8 versus 93.7 +/- 10.2, P <0.01). These results demonstrate that acute hyperglycemia does not modify plasma fibrinolysis in elderly subjects. The decrease of plasma concentration of vWF in IGT elderly subjects requires cautious interpretation and further extensive investigations.

Effects of a moderate-intensity aerobic program on blood viscosity, platelet aggregation and fibrinolytic balance in young and middle-aged sedentary subjects.

Regular physical activity is associated with reduced risk of cardiovascular disease although the mechanisms are unclear. Recent population-based studies suggest that the effect of physical activity may be at least partly a result of action on hemostasis. We tested the hypothesis that moderate-intensity aerobic training improves fibrinolytic activity and reduces platelet aggregation and blood viscosity. In 15 young (11 males and four females; age, 24-32 years) and 15 middle-aged (11 males and four females; age, 45-65 years) healthy, non-smoker, sedentary subjects, the maximum oxygen consumption, adenosine diphosphate-induced platelet aggregation, tissue plasminogen activator and plasminogen activator inhibitor type 1, antigen, hematocrit and blood viscosity were measured at baseline and after 12 weeks of aerobic exercise training (40 min three times a week at a training intensity adjusted to 60% of the individual heart rate reserve). After training, the maximum oxygen consumption was increased by 9% (P < 0.01) in the young group and by 7.3% (P < 0.05) in the middle-aged group. Adenosine diphosphate-platelet aggregation significantly decreased in the young (-30%; P < 0.05). The middle-aged group showed a 10.4% decrease in hematocrit (P < 0.05), and a 11.6 and 16.6% decrease in blood viscosity at 450/s and at 90/s rates of shear, respectively (P < 0.05), while the plasminogen activator inhibitor type 1 antigen plasma level increased 135% (P < 0.01). These data, some not consistent with others, only partially support the hypothesis that the beneficial effects of physical activity result from action on hemostatic balance. In particular, the changes in the fibrinolytic system in middle-aged subjects might suggest increased thrombotic risk. Thus a simple, straightforward conclusion is not possible at present, and further studies are required.

5.3 Global challenges in research and strategic planning.

Health sciences research is experiencing dramatic progress. How can dental schools throughout the world best make these research advances relevant for dental students, as well as providing them with the means to assess and utilize the research advances that will occur in the future? This complex question presents a critical challenge to the dental educational community. Research is clearly integral to the mission of dental education. By providing dental students with active learning strategies, dental educators can inculcate the ability for independent scientific thinking and thereby develop reflective as well as technically competent practitioners. However, there is a shortage of well-trained individuals to fill faculty and research positions in certain parts of the world. Global networks for mutual information exchange are imperative to overcome resource limitations in individual institutions, as is dedicated funding for research in the dental educational setting.

Immunohistochemistry of c-fos in Mouse Brain During Postnatal Development: Basal Levels and Changing Response to Metrazol and Kainate Injection.

Levels and cellular distribution of FOS, the product of c-fos (onco)gene, were studied by immunohistochemistry during the development of mouse brain at rest and after the administration of convulsants. Basal FOS immunoreactivity became detectable only after postnatal day 20 (P20). Metrazol and kainate at the appropriate doses induced convulsions at all ages but, in both cases, FOS accumulated in limbic areas (particularly in the dentate gyrus) only after a certain age: P20 for kainate and P30 for Metrazol. Surprisingly, considering the different molecular targets of Metrazol and kainate, respectively, and the different type of convulsions elicited, the cell groups in the limbic areas in which FOS increased were the same in the two cases. These results suggest that both drugs produced FOS increase by finally activating the same circuit. During ontogeny, the ability to accumulate FOS, which appears after P20, could be the sign of the attained maturity of signal transduction mechanisms in the cells of the hippocampal formation; endogenous signals originating from the activity of the nervous system increase the basal FOS levels and exogenous signals (i.e. like those given, probably locally, by kainate) further increase these levels. Metrazol manifests its capability to induce FOS accumulation only at later ages. We suggest that this occurs because the Metrazol target is probably distant from the hippocampal region and thus the maturity of a nerve pathway(s) is also required for c-fos induction.