Anti-proliferative activity of oral anti-hyperglycemic agents on human vascular smooth muscle cells: thiazolidinediones (glitazones) have enhanced activity under high glucose conditions

Background: Inhibition of vascular smooth muscle cell (vSMC) proliferation by oral anti-hyperglycemic agents may have a role to play in the amelioration of vascular disease in diabetes. Thiazolidinediones (TZDs) inhibit vSMC proliferation but it has been reported that they anomalously stimulate [3H]-thymidine incorporation. We investigated three TZDs, two biguanides and two sulfonylureas for their ability of inhibit vSMC proliferation. People with diabetes obviously have fluctuating blood glucose levels thus we determined the effect of media glucose concentration on the inhibitory activity of TZDs in a vSMC preparation that grew considerably more rapidly under high glucose conditions. We further explored the mechanisms by which TZDs increase [3H]-thymidine incorporation. Methods: VSMC proliferation was investigated by [3H]- thymidine incorporation into DNA and cell counting. Activation and inhibition of thymidine kinase utilized short term [3H]- thymidine uptake. Cell cycle events were analyzed by FACS

Potgrondproef met 12-10-18 bij tomaat

<p><b>Copyright information:</b></p><p>Taken from "Anti-proliferative activity of oral anti-hyperglycemic agents on human vascular smooth muscle cells: thiazolidinediones (glitazones) have enhanced activity under high glucose conditions"</p><p>http://www.cardiab.com/content/6/1/33</p><p>Cardiovascular Diabetology 2007;6():33-33.</p><p>Published online 28 Oct 2007</p><p>PMCID:PMC2211460.</p><p></p>e mean ± SEM, *P < 0.05 PDGF. B. Human vSMCs were treated with metformin (10–300 μM) and phenformin (10–300 μM) in the presence of 5% serum for 3 days and then counted on a Coulter counter. Data represent the mean ± SEM from 2 experiments in triplicate **P < 0.01, ***P < 0.001 the 5% FBS

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Clinical thiazolidinediones as PPARγ ligands with the potential for the prevention of cardiovascular disease in diabetes

Thiazolidinediones (TZDs) are PPARγ ligands and the newest class of agents in routine clinical practice for the treatment of hyperglycemia in type 2 diabetes. The prime reason for treating hyperglycemia and related aspects of the metabolic syndrome is to prevent accelerated cardiovascular disease (CVD) in diabetes. The formation and subsequent rupture of atherosclerotic "plaques", establishes CVD as the major cause of premature mortality in diabetes. Metabolically, TZDs act as insulin sensitizers resulting in improved glucose uptake, lower blood glucose and reduced hyperinsulinemia, however, they also appear to have beneficial direct vascular actions. TZDs have a range of actions directly on vascular cells and the predominance of the reported actions is potentially beneficial. TZDs inhibit vascular smooth muscle cell proliferation, inhibit the expression of adhesion molecules and modify the structure of vascular proteoglycans in a manner that results in reduced lipid binding. These actions manifest as reduced tipid deposition in the vessels of animals with experimental diabetes and atherosclerosis. Early clinical data indicates that TZDs may prevent or delay CVD including atherosclerosis and restenosis following coronary angiography. TZDs may be the first class of oral hypoglycemic agents with significant anti-atherogenic effects to combat one of the major complications of diabetes

Anti-proliferative activity of oral anti-hyperglycemic agents on human vascular smooth muscle cells: thiazolidinediones (glitazones) have enhanced activity under high glucose conditions-2

<p><b>Copyright information:</b></p><p>Taken from "Anti-proliferative activity of oral anti-hyperglycemic agents on human vascular smooth muscle cells: thiazolidinediones (glitazones) have enhanced activity under high glucose conditions"</p><p>http://www.cardiab.com/content/6/1/33</p><p>Cardiovascular Diabetology 2007;6():33-33.</p><p>Published online 28 Oct 2007</p><p>PMCID:PMC2211460.</p><p></p>ine over 4 min was assessed. The results show the effects of two identical experiments in duplicate. B. Shows concomitant data for routine assay of [H]-thymidine into DNA (see methods for details)

Anti-proliferative activity of oral anti-hyperglycemic agents on human vascular smooth muscle cells: thiazolidinediones (glitazones) have enhanced activity under high glucose conditions-4

<p><b>Copyright information:</b></p><p>Taken from "Anti-proliferative activity of oral anti-hyperglycemic agents on human vascular smooth muscle cells: thiazolidinediones (glitazones) have enhanced activity under high glucose conditions"</p><p>http://www.cardiab.com/content/6/1/33</p><p>Cardiovascular Diabetology 2007;6():33-33.</p><p>Published online 28 Oct 2007</p><p>PMCID:PMC2211460.</p><p></p>e mean ± SEM, *P < 0.05 PDGF. B. Human vSMCs were treated with metformin (10–300 μM) and phenformin (10–300 μM) in the presence of 5% serum for 3 days and then counted on a Coulter counter. Data represent the mean ± SEM from 2 experiments in triplicate **P < 0.01, ***P < 0.001 the 5% FBS