Capillary Regeneration in Scleroderma: Stem Cell Therapy Reverses Phenotype?

BACKGROUND. Scleroderma is an autoimmune disease with a characteristic vascular pathology. The vasculopathy associated with scleroderma is one of the major contributors to the clinical manifestations of the disease. METHODOLOGY/PRINCIPAL FINDINGS. We used immunohistochemical and mRNA in situ hybridization techniques to characterize this vasculopathy and showed with morphometry that scleroderma has true capillary rarefaction. We compared skin biopsies from 23 scleroderma patients and 24 normal controls and 7 scleroderma patients who had undergone high dose immunosuppressive therapy followed by autologous hematopoietic cell transplant. Along with the loss of capillaries there was a dramatic change in endothelial phenotype in the residual vessels. The molecules defining this phenotype are: vascular endothelial cadherin, a supposedly universal endothelial marker required for tube formation (lost in the scleroderma tissue), antiangiogenic interferon α (overexpressed in the scleroderma dermis) and RGS5, a signaling molecule whose expression coincides with the end of branching morphogenesis during development and tumor angiogenesis (also overexpressed in scleroderma skin. Following high dose immunosuppressive therapy, patients experienced clinical improvement and 5 of the 7 patients with scleroderma had increased capillary counts. It was also observed in the same 5 patients, that the interferon α and vascular endothelial cadherin had returned to normal as other clinical signs in the skin regressed, and in all 7 patients, RGS5 had returned to normal. CONCLUSION/SIGNIFICANCE. These data provide the first objective evidence for loss of vessels in scleroderma and show that this phenomenon is reversible. Coordinate changes in expression of three molecules already implicated in angiogenesis or anti-angiogenesis suggest that control of expression of these three molecules may be the underlying mechanism for at least the vascular component of this disease. Since rarefaction has been little studied, these data may have implications for other diseases characterized by loss of capillaries including hypertension, congestive heart failure and scar formation.Scleroderma Research Foundatio

Serum Adhesion Molecule Levels as Prognostic Markers in Patients with Early Systemic Sclerosis: A Multicentre, Prospective, Observational Study

Objective: To assess the utility of circulating adhesion molecule levels as a prognostic indicator of disease progression in systemic sclerosis (SSc) patients with early onset disease. Methods: Ninety-two Japanese patients with early onset SSc presenting with diffuse skin sclerosis and/or interstitial lung disease were registered in a multicentre, observational study. Concentrations of intercellular adhesion molecule (ICAM) -1, E-selectin, L-selectin, and P-selectin in serum samples from all patients were measured by enzyme-linked immunosorbent asssay (ELISA). In 39 patients, adhesion molecule levels were measured each year for four years. The ability of baseline adhesion molecule levels to predict subsequent progression and severity in clinical and laboratory features were evaluated statistically. Results: At their first visit, serum levels of ICAM-1, E-selection, P-selectin were significantly elevated and serum L-selectin levels were significantly reduced in patients with SSc compared with healthy controls. Overall, serum ICAM-1 levels at each time point were significantly inversely associated with the %vital capacity (VC) of the same time and subsequent years by univariate analysis. The initial serum ICAM-1 levels were significantly inversely associated with the %VC at the fourth year by multiple regression analysis. The initial serum P-selectin levels were significantly associated with the health assessment questionnaire disability index (HAQ-DI) at the fourth year by multiple regression analysis. Initial adhesion molecule levels were not significantly associated with other clinical features including skin thickness score. Baseline adhesion molecule levels were not significantly associated with subsequent rate of change of clinical parameters. Conclusion: In patients with SSc, serum levels of ICAM-1 and P-selectin may serve as prognostic indicators of respiratory dysfunction and physical disability, respectively. Further longitudinal studies of larger populations are needed to confirm these findings

Antithrombotic therapy of Cerebral cavernous malformations /

Cavernous malformations are recognized as the most common vascular anomalies in the brain, that often lead to hemorrhage with neurological symptoms. Usually the treatment is surgical removal or stereotactic radiotherapy. We present a case of a slow-flow vascular anomaly located in the cavernous sinus with recurrent partial thrombotic areas. Inspired by treatment of peripheral venous anomalies antithrombotic therapy was initiated instead of surgery or stereotactic radiotherapy. This led to complete spontaneous resolution of the lesion and normalization of symptoms within nine months. The patient never showed any symptoms over a period of eight years while continuing antithrombotic therapy. Based on this case this therapy may be a reasonable approach to treat intracerebral venous anomalies

Steady Aerodynamics of Miniature Trailing-Edge Devices in Transonic Flows

The paper describes results of a comprehensive experimental and numerical investigation of the aerodynamics of miniature trailing-edge devices (MiniTEDs) on a supercritical airfoil at transonic speeds. The influence of MiniTEDs on the two-dimensional airfoil flow and on the aerodynamic coefficients is presented in detail for the Gurney flap, the split flap and the divergent trailing-edge. The influence of geometry parameters is discussed for the Gurney flap height, the split flap deflection angle and the MiniTED position, as well as for different types of perforation. The use of MiniTEDs as adaptive elements is presented for drag-optimal operation and is compared to the performance of a flexible trailing-edge. The influence of different freestream parameters is discussed for the Mach number and the Reynolds number