AlphaV beta3 (αvβ3) integrin inhibition reduces leukocyte–endothelium interaction in a pressure-induced reperfusion model

The leukocyte-endothelium interaction is known to contribute to reperfusion injury, which is considered to participate in the pathophysiology of pressure ulcers, and integrin alphaV beta3 (alphavbeta3) has been shown to mediate the processes of cellular adhesion in various types of cells. This study aims to clarify leukocyte behavior in our original microcirculatory pressure-induced reperfusion model, which can visualize the microcirculation in vivo. We also estimated the effect of alphavbeta3 integrin inhibition on the reduction of the leukocyte-endothelium interaction. Mice with dorsal skinfold chambers were divided into three groups: the baseline group (n=6), in which animals received no compression; the compression-reperfusion group (n=6), in which animals underwent 2-hour compression of the dorsal skin, followed by release, and the inhibitor-treated group (n=7), in which an alphavbeta3 inhibitor, CP4715, was administered in addition to the compression-release procedure. Staining with rhodamine 6G quantitatively visualized leukocyte behavior under the intravital fluorescent microscope. Compression-reperfusion induced a significant increase in rolling, sticking, and extravasation of the leukocytes. Treatment with the inhibitor strikingly reduced leukocyte sticking and extravasation. The present experiment has provided evidence that alphavbeta3 inhibition reduces leukocyte-endothelium interaction in our original pressure-induced reperfusion model.     

The αvβ6 integrin plays a role in compromised epidermal wound healing

The alphavbeta6 integrin is an exclusively epithelial integrin that is highly expressed during fetal development. In adult tissue, alphavbeta6 integrin is expressed during inflammation, carcinogenesis, and in wound healing. We previously reported that alphavbeta6 integrin is highly expressed in poorly healing human wounds and its over-expression is associated with chronic wounds in a mouse model. The objective of this study was to investigate the role of alphavbeta6 integrin in compromised wound healing induced by hydrocortisone treatment or aging by using young and old mice deficient in or overexpressing the beta6 integrin subunit in the epidermis. Untreated aged beta6 integrin-deficient (beta6-/-) animals showed a significant delay in wound healing when compared to their age-matched controls or younger beta6-/- mice. The most significant delay was observed at the stages where granulation tissue deposition was occurring. Hydrocortisone treatment significantly delayed wound healing in wild-type and beta6 integrin-deficient mice in comparison with the untreated controls. However, hydrocortisone treatment in beta6 integrin overexpressing animals did not cause a significant delay in wound healing. The results of this study suggest that alphavbeta6 integrin plays an important role in wound healing in animals compromised by either age or stress mimicked by hydrocortisone.     

Ventilation imaging of the lung: Comparison of hyperpolarized helium-3 MR imaging with Xe-133 scintigraphy

RATIONALE AND OBJECTIVES: To compare hyperpolarized helium-3 (HHe) magnetic resonance imaging (MRI) of the lung with standard Xe-133 lung ventilation scintigraphy. MATERIALS AND METHODS: We performed a retrospective review of 15 subjects who underwent HHe MRI and Xe-133 lung ventilation imaging. Coronal MRI sections were acquired after a single inhalation of HHe gas, and standard posterior planar lung ventilation scintigraphy was performed during continuous breathing of Xe-133 gas. The first breath scintigram of each patient was compared with a composite MR image composed of the sum of the individual MR images and with the individual helium-3 MR images. Ventilation defects on the two imaging modalities were compared for size, conspicuity, and concordance in presence and location. Assessment was done separately for each of four lung quadrants. RESULTS: Comparing the composite HHe MR images with Xe-133 scintigraphy, ventilation defect size, conspicuity and concordance were the same in 67% (40/60), 63% (38/60), and 62% (37/60) quadrants, respectively. Comparing the individual HHe MR image sections with the Xe-133 ventilation scan, there was concordance between the ventilation defects in 27% (16/60) of quadrants. More defects were identified on the individual HHe MR images in 62% (37/60) of quadrants. CONCLUSION: There was good agreement between composite HHe MR image and first breath Xe-133 scintigraphic images, supporting the widely held assumption that HHe MRI likely depicts first breath lung ventilation.     

Pharmacy customers’ views and experiences of using pharmacies which provide needle exchange services in Aberdeen and Glasgow, Scotland

Community pharmacists contribution to the management of drug problems is considerable. As the use of illicit drugs has increased, pharmacists have come under increasing pressure to offer services to problem drug users. However, there is concern among some pharmacists that offering such services may deter other customers. There is particular concern among some pharmacists about needle exchange services. Only 9.5% of Scottish pharmacies offer needle exchange services compared to 69% which are dispensing methadone (57% of which supervise methadone consumption). Qualitative interviews were used in a purposive sample of 10 pharmacies in Scotland. Eight customers were interviewed in each pharmacy to ascertain pharmacy customers’ views on these services. The majority of customers were supportive of these services. Customers were often unaware that the pharmacy they were interviewed in was offering services for people with drug problems. Pharmacy customers were more knowledgeable about, and more supportive, of needle exchange services than they were of methadone. This was because they believed needle exchange services helped to reduce the amount of discarded needles in public places. Pharmacy customers also recognised that needle exchange helped reduce the spread of disease. These findings should be used to encourage more pharmacists to offer needle exchange services.     

Use of amniotic membrane transplantation in the treatment of venous leg ulcers

Amniotic membrane (AM), the most internal placental membrane, has unique properties including antiadhesive effects, bacteriostatic, wound protection and pain-reduction properties, as well as epithelialization initialization capacities. Furthermore, AM is widely available and less costly than other bioengineered skin substitutes. In a prospective pilot study, we evaluated the safety, feasibility, and the effects on healing of AM graft in 15 patients with chronic venous leg ulcers. AM grafts were prepared from placentas harvested during cesarean section. All grafted AM had adhered to the wound bed 7 days after being applied with a 100% engraftment rate. The percentage of granulation tissue increased significantly (from 17% on day 0 to 69% on day 14, p<0.0001), along with a significant decrease of fibrinous slough (from 36% at day 0 to 16% at day 14, p<0.001). A significant clinical response occurred in 12 patients (80%) including complete healing (20%) in three during the 3-month follow-up period. The ulcer surface area decreased significantly from a mean value (+/- standard deviation) of 4.59 +/- 2.49 cm(2) at baseline to 2.91+/-2.01 cm(2) on day 30 (p<0.001). All patients experienced a significant reduction of ulcer-related pain rapidly after AM transplantation. No adverse events were recorded. AM transplantation seems to function as a safe substrate, promoting proper epithelialization while suppressing excessive fibrosis. Further advantages of biotherapy with AM are its easy and low-cost production, and that it can be applied as an ambulatory treatment without immobilization. AM transplantation may thus be considered to be an alternative method for treating chronic leg ulcers.