Platelet-dependent primary hemostasis promotes selectin- and integrin- mediated neutrophil adhesion to damaged endothelium under flow conditions

Co-localization of blood platelets and granulocytes at sites of hemostasis and inflammation has triggered an intense interest in possible interactions between these cellular processes and induction of vessel wall injury. Leukocyte adhesion to endothelial cells decreases with increasing shear and is dependent on an initial rolling phase mediated by selectins. We hypothesized that flow-dependent platelet adhesion at an injured vessel wall will lead to P-selectin expression by platelets, thus mediating leukocyte co-localization. A perfusion chamber was used in which flowing whole blood induced platelet adhesion to a subendothelial matrix (ECM) of cultured human umbilical vein endothelial cells (HUVEC). We compared neutrophil (polymorphonuclear leukocyte [PMN]) interactions with HUVEC and their ECM with and without adhered platelets. PMNs adhered predominantly to ECM-adhered platelets and not to endothelial cells. ECM alone did not support PMN adhesion under flow conditions. PMN adhesion to unstimulated HUVEC was only substantial at low shear (up to 200 cells/mm2 at shear stress 80 mPa). In marked contrast, PMN adhesion to ECM-adhered platelets was dramatically increased, and adhesion was demonstrated at much higher shear stress (up to 640 mPa). Studies with specific antibodies showed that the platelet-dependent neutrophil adhesion was selectin-mediated. Inhibition of P-selectin caused a marked inhibition of adhesion at high shear stress, whereas the role of leukocyte L-selectin was less pronounced. beta2-Integrin-blocking antibodies inhibited static neutrophil adhesion. fMLP induced L-selectin shedding from leukocytes, resulting in decreased leukocyte adhesion. In conclusion, platelet- dependent hemostasis at the ECM appears to be a powerful intermediate in neutrophil-vessel wall interactions at shear stresses that normally do not allow neutrophil adhesion to intact endothelium.     

Rapidly deteriorating course in Dutch hereditary spastic paraplegia type 11 patients

Although SPG11 is the most common complicated hereditary spastic paraplegia, our knowledge of the long-term prognosis and life expectancy is limited. We therefore studied the disease course of all patients with a proven SPG11 mutation as tested in our laboratory, the single Dutch laboratory providing SPG11 mutation analysis, between 1 January 2009 and 1 January 2011. We identified nine different SPG11 mutations, four of which are novel, in nine index patients. Eighteen SPG11 patients from these nine families were studied by means of a retrospective chart analysis and additional interview/examination. Ages at onset were between 4 months and 14 years; 39% started with learning difficulties rather than gait impairment. Brain magnetic resonance imaging showed a thin corpus callosum and typical periventricular white matter changes in the frontal horn region (known as the ‘ears-of the lynx''-sign) in all. Most patients became wheelchair bound after a disease duration of 1 to 2 decades. End-stage disease consisted of loss of spontaneous speech, severe dysphagia, spastic tetraplegia with peripheral nerve involvement and contractures. Several patients died of complications between ages 30 and 48 years, 3–4 decades after onset of gait impairment. Other relevant features during the disease were urinary and fecal incontinence, obesity and psychosis. Our study of 18 Dutch SPG11-patients shows the potential serious long-term consequences of SPG11 including a possibly restricted life span.     

May the Gender of a Parent Influence Assessment of Health‐Related Quality of Life,Family Impact and Severity of Atopic Dermatitis in Children?

Abstract:   Despite it is well known that atopic dermatitis has severe negative impact on child's and family life there is little information concerning gender influence on health-related quality of life assessment. We did not find any statistically significant gender differences in assessment of the Infant's Dermatitis Quality of Life Index and the Dermatitis Family Impact and its separate items. Our results showed that choice of parent who should fill in the Infant's Dermatitis Quality of Life Index and the Dermatitis Family Impact cannot significantly influence the results of clinical studies, but inside couples spouses could have alternative view, which is not associated with gender.     

An Infant with Acrodermatitis Continua of Hallopeau: Successful Treatment with Thalidomide and UVB Therapy

Abstract:   Acrodermatitis Continua of Hallopeau is a rare, chronic, recurrent disorder classified as a form of pustular psoriasis, and most cases affect one or two digits. It tends to be resistant to both topical and systemic treatments for psoriasis. We present an infant with Acrodermatitis Continua of Hallopeau affecting nineteen nails, with an excellent response to the combination of thalidomide and ultraviolet B phototherapy.     

Intravascular Electroporation Markedly Attenuates Neointima Formation After Balloon Injury of the Carotid Artery in the Rat

The present study examined the use of electroporation (pulsed electric field application) to temporarily permeabilize vascular cell membranes and thereby deliver drugs directly into cells of the vessel wall to treat focal cardiovascular diseases (e.g., postangioplasty restenosis). A unique intravascular porous balloon electroporation catheter has been designed specifically to enhance drug uptake directly into the arterial wall. The effect of heparin on neointimal growth following balloon-induced injury of the carotid arteries of rats was used as a measure of effective drug delivery. Histomorphometrical analysis of arteries showed that neointimal growth and lumen loss were significantly inhibited by heparin in combination with electroporation, but not by heparin delivered without electroporation. We conclude that the application of electroporation technology may be a viable approach to intramural drug delivery of potential therapeutic compounds for the treatment of neointimal growth and negative remodeling during postangioplasty restenosis.