Abstract-Angiotensin II (Ang II) induces reactive oxygen species (ROS) production by human vascular smooth muscle cells (hVSMCs). ROS have been implicated in the development of both acute stress-induced premature senescence (SIPS) and chronic replicative senescence. Global oxidative DNA damage triggers SIPS and telomere DNA damage accelerates replicative senescence, both mediated via p53. This study tests the hypothesis that DNA is an important target for Ang II-induced ROS leading to senescence via telomere-dependent and independent pathways. DNA damage was quantified using the Comet assay, telomere DNA length by Southern blotting and hVSMC senescence by senescence-associated ␤-galactosidase staining. Exposure to Ang II increased DNA damage in hVSMCs within 4 hours. Inhibition by an AT 1 receptor antagonist (losartan metabolite: E3174) or catalase, confirmed that Ang II-induced DNA damage was AT 1 receptor-mediated, via the induction of ROS. Acute exposure to Ang II resulted in SIPS within 24 hours that was prevented by coincubation with E3174 or catalase. SIPS was associated with increased p53 expression but was not dependent on telomere attrition because overexpression of human telomerase did not prevent Ang II-induced SIPS. Exposure to Ang II over several population doublings accelerated the rate of telomere attrition (by Ͼ2-fold) and induced premature replicative senescence of hVSMCs-an effect that was also attenuated by E3174 or catalase. These data demonstrate that Ang II-induced ROS-mediated DNA damage results in accelerated biological aging of hVSMCs via 2 mechanisms: (1) Acute SIPS, which is telomere independent, and (2) accelerated replicative senescence which is associated with accelerated telomere attrition.

The findings demonstrate that leucocyte DNA content is predictive of vascular telomere content and is an accurate surrogate for human vascular age.

Objective Short telomeres are associated with adult cardiovascular disease. Our aim was to determine whether small-for-gestationalage (SGA) newborns have shortened telomeres compared with appropriately grown controls.Design Prospective cohort study.Setting Large tertiary referral unit in Trent, UK.Population Seventy-two women who delivered at 35-42 weeks of gestation were recruited; 34 delivered SGA babies (less than or equal to the third birthweight centile) and 38 had appropriately grown babies (greater than the tenth centile).Methods Maternal and cord blood samples were collected at delivery. A Southern blot of DNA from these samples was hybridised with a 32 P-labelled telomeric probe and telomere length was measured.Main outcome measures Mean maternal and newborn telomere length.Results Maternal and newborn telomere lengths were significantly correlated in both the SGA and the control groups (r 2 = 0.25, P < 0.0001). Telomere lengths were similar in both maternal (control 8.41 ± 0.9 kb versus SGA 8.29 ± 1.0 kb, P = 0.57) and newborn (control 10.36 ± 1.5 kb versus SGA 10.33 ± 1.3 kb, P = 0.93) cohorts in the two groups.Conclusions Intrauterine events associated with impaired fetal growth do not appear to be associated with increased telomere shortening.

Objective. To examine the rates of and risk factors for neutropenia together with the dynamics of neutrophil and other white cell subset counts in a cohort of patients treated with a tumor necrosis factor (TNF) inhibitor for inflammatory arthritis. Methods. We performed a retrospective cohort study examining the association between baseline demographics, clinical features, medications used, and development of neutropenia, and behavior of neutrophil and other white cell subset counts during TNF inhibitor therapy. Results. In 367 patients (298 [81.2%] with rheumatoid arthritis, 38 [10.4%] with ankylosing spondylitis, and 31 [8.4%] with psoriatic arthritis), 69 (18.8%) had at least one episode of neutropenia (<2.0 ؋ 10 9 /liter) during TNF inhibitor therapy, and of these, 6% developed serious infections secondary to neutropenia. There was no significant difference in disease, demographic, or drug variables between patients with and without neutropenia. However, patients with neutropenia had significantly lower baseline neutrophil counts (4.2 ؋ 10 9 /liter; 95% confidence interval [95% CI] 3.8, 4.6 versus 6.2 ؋ 10 9 /liter; 95% CI 6.0, 6.5), and a previous history of neutropenia while receiving disease-modifying antirheumatic drugs increased the risk while receiving TNF inhibitors (hazard ratio 2.97; 95% CI 1.69, 5.25). A significant drop in mean neutrophil count (1.12 ؋ 10 9 /liter; 95% CI 0.92, 1.32) was observed after 2 weeks of TNF inhibitor therapy. Other white cell subsets tended to significantly increase. Conclusion. TNF inhibitor therapy is associated with a significant reduction in peripheral blood neutrophil count, leading to 19% of patients becoming neutropenic. Risk of neutropenia is significantly higher in patients with a low baseline neutrophil count or previous history of neutropenia. We suggest that patients receiving TNF inhibitor therapy would benefit from regular complete blood cell count monitoring.

Noisy Miners ( Manorina melanocephala ) are aggressive Australian honeyeaters that dominate many areas of remnant vegetation and forest edges from which they competitively exclude small birds. A similar domination can also occur in planted wildlife corridors. The aim of this study was to determine which corridor plantings encouraged the presence of small native birds in regions where Noisy Miners dominate. Six vegetation mixes were investigated in the main study: eucalypts with and without shrubby understorey; acacia with and without shrubby understorey; exotic conifer; and exotic deciduous trees. A supplementary study then examined sites with a mixture of eucalypt and acacia trees with a shrubby understorey. The findings showed that Noisy Miners dominated corridors of eucalypts, virtually excluding small birds, whereas native acacias, exotic conifer and exotic deciduous corridors had small birds and no resident Noisy Miners. The greatest abundance and richness of small birds occurred in plantings combining eucalypts with at least 15% acacias, in this case bipinnate species. Given these results, it is recommended that eucalypt plantings should be supplemented with both acacias (preferably bipinnate) and a shrubby understorey.