Controlled release strategies for bone, cartilage, and osteochondral engineering: part I: recapitulation of native tissue healing and variables for the design of delivery systems

The potential of growth factors to stimulate tissue healing through the enhancement of cell proliferation, migration, and differentiation is undeniable. However, critical parameters on the design of adequate carriers, such as uncontrolled spatiotemporal presence of bioactive factors, inadequate release profiles, and supraphysiological dosages of growth factors, have impaired the translation of these systems onto clinical practice. This review describes the healing cascades for bone, cartilage, and osteochondral interface, highlighting the role of specific growth factors for triggering the reactions leading to tissue regeneration. Critical criteria on the design of carriersfor controlled release of bioactive factors are also reported, focusing on the need to provide a spatiotemporal control over the delivery and presentation of these molecules.The authors thank Fundacao para a Ciencia e Tecnologia for V.E.Santo's PhD grant (SFRH/BD/39486/2007). This work was carried out under the scope of the European FP7 Project Find and Bind (NMP4-SL-2009-229292) and Project MIT/ECE/0047/2009

An aggravated trajectory of depression and anxiety co-morbid with hepatitis C: : A 21 to 62 month follow-up study in 61 South Australian outpatients

BACKGROUND: This study aimed to explore the course of depression and anxiety in chronic hepatitis C patients. METHODS:   Data were combined from two studies: (1) Hospital Anxiety and Depression Scale (HADS) scores in 395 consecutive Australian outpatients from 2006 to 2010 formed the baseline measurement; and (2) Depression Anxiety Stress Scales (DASS) scores in a survey of a sub-sample of these patients in 2011 formed the follow-up measurement. After converting DASS to HADS scores, changes in symptom scores and rates of case-ness (≥8), and predictors of follow-up symptoms were assessed. RESULTS:   Follow-up data were available for 61 patients (70.5% male) whose age ranged from 24.5 to 74.6 years (M=45.6). The time to follow-up ranged from 20.7 to 61.9 months (M=43.8). Baseline rates of depression (32.8%) and anxiety (44.3%) increased to 62.3% and 67.2%, respectively. These findings were confirmed, independent of the conversion, by comparing baseline HADS and follow-up DASS scores with British community norms. Baseline anxiety and younger age predicted depression, while baseline anxiety, high school non-completion, and single relationship status predicted anxiety. CONCLUSION:  This study demonstrated a worsening trajectory of depression and anxiety. Further controlled and prospective research in a larger sample is required to confirm these findings

Fibrinogen as an inflammatory mediator at the Saphenous Vein Endothelium

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN030508 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Development of an in vitro model to study the response of saphenous vein endothelium to pulsatile arterial flow and circumferential deformation

Objectives:To develop an in vitro model of human saphenous vein bypass to facilitate study of the early adaptive responses of venous endothelium to arterial flow conditions.Design, material and methods:Segments of human saphenous vein (with or without external polytetrafluoroethylene (PTFE) stents to limit circumferential and radial deformation) were mounted in a bypass circuit and subjected to pulsatile flow with oxygenated Krebs solution to simulate arterial or venous flow conditions for a period of 90 min. The viability of the vein was assessed by the tissue ATP concentration and vasomotor responses to phenylephrine, sodium nitroprusside and bradykinin (endothelium-dependent). Immunohistochemistry was used to assess both endothelial preservation (CD31) and the expression of proteins involved in leukocyte adhesion: E-selectin, P-selectin and ICAM-1. Freshly excised veins were used as controls.Results:The concentration of ATP was 320 ± 11 nmol/g in freshly excised vein (n = 8) and following exposure to the arterial flow circuit increased to 566 ± 60 nmol/g (n = 8, paired t-test, p = 0.003) in unstented veins and to 421 ± 49 nmol/g (n = 8, paired t-test, p = 0.002) in externally stented veins (with PTFE). Both endothelium-dependent and sodium nitroprusside-induced vasodilatation responses were preserved after veins were exposed to the arterial flow circuit, but the sensitivity to phenylephrine was increased: EC50 decreasing from 9μm to 1μm, p = 0.008. There was a 5–10% decrease in staining area for CD31 after veins, stented or unstented, were exposed to the arterial flow circuit. However, after exposure to the arterial flow circuit, the staining area ratio for ICAM-1/CD31, which remained unchanged in externally stented veins, increased two-fold in unstented veins, p>0.01: there were no changes in the staining area ratio P-selectin/CD31 and no staining for E-selectin was observed.Conclusion:Vasomotor responses and tissue ATP concentrations indicate that the viability of saphenous vein can be maintained for up to 90 min in an ex vivo flow circuit and the CD31 staining indicated endothelial preservation. This opens up the possibility of investigating the early changes in saphenous vein endothelium following exposure to arterial pressure, as at bypass surgery. First results suggest that there is rapid upregulation of the leukocyte adhesion molecule ICAM-1, which can be prevented by limiting the circumferential deformation of the vein with an external PTFE stent