Short-term inhibition of DPP-4 enhances endothelial regeneration after acute arterial injury via enhanced recruitment of circulating progenitor cells

Background

Endothelial injuries regularly occur in atherosclerosis and during interventional therapies of the arterial occlusive disease. Disturbances in the endothelial integrity can lead to insufficient blood supply and bear the risk of thrombus formation and acute vascular occlusion. At present, effective therapeutics to restore endothelial integrity are barely available.We analyzed the effect of pharmacological DPP-4-inhibition by Sitagliptin on endogenous progenitor cell-based endothelial regeneration via the SDF-1α/CXCR4-axis after acute endothelial damage in a mouse model of carotid injury.

Methods and Results

Induction of a defined endothelial injury was performed in the carotid artery of C57Bl/6 mice which led to a local upregulation of SDF-1α expression. Animals were treated with placebo, Sitagliptin or Sitagliptin + AMD3100. Using mass spectrometry we could prove that Sitagliptin prevented cleavage of the chemokine SDF-1α. Accordingly, increased SDF-1α concentrations enhanced recruitment of systemically applied and endogenous circulating CXCR4 + progenitor cells to the site of vascular injury followed by a significantly accelerated reendothelialization as compared to placebo-treated animals. Improved endothelial recovery, as well as recruitment of circulating CXCR4 + progenitor cells (CD133 +, Flk1 +), was reversed by CXCR4-antagonization through AMD3100. In addition, short-term Sitagliptin treatment did not significantly promote neointimal or medial hyperplasia.

Conclusion

Sitagliptin can accelerate endothelial regeneration after acute endothelial injury. DPP-4 inhibitors prevent degradation of the chemokine SDF-1α and thus improve the recruitment of regenerative circulating CXCR4 + progenitor cells which mediate local endothelial cell proliferation without adversely affecting vessel wall architecture.     

Reliability and validity of the German short version of the Activities specific Balance Confidence (ABC-D6) scale in older adults

The Activities specific Balance Confidence (ABC) is a questionnaire which was developed to assess falls-associated self-efficacy. The aim of this study was to evaluate reliability and validity of the German abbreviated 6-item version of the ABC scores in community-dwelling older people. The study sample included 384 subjects (age 71.1 ± 9.7). In order to determine the psychometric properties, reliability and validity were assessed through administration of the German adaptation of the ABC-D16 to participants twice, 10 days apart, and comparison of the ABC-D16 and the ABC-D6 with functional measures of balance and mobility (one-leg stance; 10 m walk; TUG; Fullerton Advanced Balance Scale (FAB)), physical activity (Physical Activity Scale for the Elderly (PASE)), physical fitness (30 s arm curl, 30 s chair stand, 6 min walk), cognition (Trail-Making-Test (TMT)), falls status, and quality of life (SF36). Factor analyses suggested a 1-factor solution for the ABC-D6 scale (explained variance 79.8%). Internal consistency (.95) and test-retest reliability (.98) for the ABC-D6 scores were excellent. Scores on the ABC-D6 were significantly lower than on the ABC-D16, but ABC-D16 and ABC-D6 scores were highly correlated (.94). There was an increasing difference in the ABC-scores between men and women with increasing age. Fallers reported lower balance confidence than non-fallers. The ABC-D6 score significantly correlated with functional measures of balance and mobility, physical activity, physical fitness, cognition, and quality of life (−.698 < r < .720). It was found that the ABC-D6 is a reliable and valid instrument to asses falls-associated self-efficacy and may be used in future research projects and clinical trials.     

The anti-inflammatory effect of milk and dairy products on periodontal cells: an in vitro approach

Clinical Oral Investigations - Milk can reduce intestinal tissue damage in colitis models, and protects infants against necrotizing enterocolitis. However, whether milk can decrease inflammation...     

Practices to support co-design processes: A case-study of co-designing a program for children with parents with a mental health problem in the Austrian region of Tyrol

Forms of collaborative knowledge production, such as community-academic partnerships (CAP), have been increasingly used in health care. However, instructions on how to deliver such processes are lacking. We aim to identify practice ingredients for one element within a CAP, a 6-month co-design process, during which 26 community- and 13 research-partners collaboratively designed an intervention programme for children whose parent have a mental illness. Using 22 published facilitating and hindering factors for CAP as the analytical framework, eight community-partners reflected on the activities which took place during the co-design process. From a qualitative content analysis of the data, we distilled essential practices for each CAP factor. Ten community- and eight research-partners revised the results and co-authored this article. We identified 36 practices across the 22 CAP facilitating or hindering factors. Most practices address more than one factor. Many practices relate to workshop design, facilitation methods, and relationship building. Most practices were identified for facilitating ‘trust among partners’, ‘shared visions, goals and/or missions’, ‘effective/frequent communication’, and ‘well-structured meetings’. Fewer practices were observed for ‘effective conflict resolution’, ‘positive community impact’ and for avoiding ‘excessive funding pressure/control struggles’ and ‘high burden of activities’. Co-designing a programme for mental healthcare is a challenging process that requires skills in process management and communication. We provide practice steps for delivering co-design activities. However, practitioners may have to adapt them to different cultural contexts. Further research is needed to analyse whether co-writing with community-partners results in a better research output and benefits for participants.     

Joint Congress of European Neurology 31 May–3 June 2014 Istanbul,Turkey

Neuromyelitis optica (NMO, Devic’s syndrome), long considered a clinical variant of multiple sclerosis, is now regarded as a distinct disease entity. Major progress has been made in the diagnosis and treatment of NMO since aquaporin-4 antibodies (AQP4-Ab; also termed NMO-IgG) were first described in 2004. In this review, the Neuromyelitis Optica Study Group (NEMOS) summarizes recently obtained knowledge on NMO and highlights new developments in its diagnosis and treatment, based on current guidelines, the published literature and expert discussion at regular NEMOS meetings. Testing of AQP4-Ab is essential and is the most important test in the diagnostic work-up of suspected NMO, and helps to distinguish NMO from other autoimmune diseases. Furthermore, AQP4-Ab testing has expanded our knowledge of the clinical presentation of NMO spectrum disorders (NMOSD). In addition, imaging techniques, particularly magnetic resonance imaging of the brain and spinal cord, are obligatory in the diagnostic workup. It is important to note that brain lesions in NMO and NMOSD are not uncommon, do not rule out the diagnosis, and show characteristic patterns. Other imaging modalities such as optical coherence tomography are proposed as useful tools in the assessment of retinal damage. Therapy of NMO should be initiated early. Azathioprine and rituximab are suggested as first-line treatments, the latter being increasingly regarded as an established therapy with long-term efficacy and an acceptable safety profile in NMO patients. Other immunosuppressive drugs, such as methotrexate, mycophenolate mofetil and mitoxantrone, are recommended as second-line treatments. Promising new therapies are emerging in the form of anti-IL6 receptor, anti-complement or anti-AQP4-Ab biologicals.     

Mitochondrial repair of 8-oxoguanine and changes with aging

Reactive oxygen species (ROS) are formed in all living organisms as a by-product of normal metabolism (endogenous sources) and as a consequence of exposure to environmental compounds (exogenous sources). Endogenous ROS are largely formed during oxidative phosphorylation in the mitochondria and, therefore, mitochondrial DNA (mtDNA) is at particularly high risk of ROS-induced damage. Mitochondria are essential for cell viability, and oxidative damage to mtDNA has been implicated as a causative factor in a wide variety of degenerative diseases, and in cancer and aging. One of the most common oxidative DNA lesions is 7,8-dihydro-8-oxoguanine (8-oxoG), which can introduce G/C to T/A transversions after DNA replication. Oxidative DNA base lesions, including 8-oxoG, are repaired primarily by the base excision repair (BER) pathway. While we know much about how this pathway functions in processing the nuclear DNA lesions, little is yet known about BER in mitochondria. We have used a number of different approaches to explore the mechanisms of DNA damage processing in the mtDNA. We have been able to demonstrate that mammalian mitochondria efficiently remove 8-oxoG from their genome, and that the efficiency of 8-oxoG incision increases with age in rats and mice. Yet 8-oxoG accumulates in mtDNA during aging. Changes in mitochondrial function with age have been observed in several organisms and accumulation of DNA lesions in mtDNA with age may be an underlying cause for numerous age-associated diseases including cancer.