Thway by way ofnuclear factor kappa-beta (NFk-) translocation [10]. However, since TNF- and IL-1 have independent post-translational regulation mechanisms and endogenous inhibitors, these could account for differences in serum cytokine concentrations [42?5]. Therefore, treatment regimens targeted at reducing specific pro-inflammatory mediators involved in local inflammation in SCD may be useful in the management of sickle leg ulcers. The involvement of the pro-inflammatory cytokines IL-1 and TNF- in promoting endothelial adhesiveness, leukocyte activation [46] and the coagulation cascade [47] could render them potent mediators of episodic vasoocclusion in sickle cell disease and in promoting chronic leg ulcers. The properties of whole blood are such that changes in the whole blood viscosity have an inverse effect on the rate of blood flow. In vitro, this has important implications as normal blood flow can always be interrupted by any or a combination of factors which affect 1527786 either shear rate or viscosity. In sickle cell blood, the abnormal rheological properties Title Loaded From File conferred by the polymerization dependent rigidification of the erythrocyte membrane are worsened by small increments in WBV. Cooperative vasoocclusion may result from clumping of rigid red cells and leucocytes and their adherence to the activated endothelium. The greater concentrations of sICAM-1, IL-1, as wells as the raised WBV in SSu compared with SSn subjects may be indicative of inflammatory mediated vaso-occlusion in the pathogenesis of sickle cell leg ulcers. While it is conceivable how the up-regulation of adhesion factors may adversely affect WBV in vivo, it is unclear how these associations may be relevant in vitro since there is no endothelium for RBC adherence. The present findings showed increased mean cell size in the ulcer group compared with HbSS controls. Meanwhile, RDW was similar between groups, suggestive of similar cell densities and therefore unlikely to be associated with the higher WBV in the ulcer patients. Acute phase increases in certain proteins with attendant decrease in haematocrit have been reported in diabetic foot ulcers [48] and Title Loaded From File arteriosclerosis obliterans [49]. Further investigations into the association between acute phase proteins and plasma viscosity among these ulcer patients may aid in explaining our WBV findings. It is possible that a significantly greater mean cell volume, although within normal limits, could be associated with greater WBV in patients with ulcers compared with those without ulcers. A lower HVR or otherwise termed `erythrocyte transport effectiveness’ [50,51] [31] describes the rheological potential of the blood and therefore serves an index for assessing the likelihood of oxygen reaching tissues in the microcirculation for a given haematocrit and WBV. However, oxygen delivery is a complex process and is ultimately determined by several other factors including pH, temperature and red cell 2,3-diphosphoglycerate concentration. The viscosity recordings in the present work were lower than reported for normal or sickle blood [28,31]. The lower values may be due to a systematic error in the cone-plate viscometer used in our study. There are no reports in the literature regarding the involvement of body mass index (BMI) in sickle leg ulceration.Inflammation and Adhesion in Chronic Leg UlcersHowever, we reported a significantly greater BMI in patients with ulcers than those without ulcers which was related a significantly great.Thway by way ofnuclear factor kappa-beta (NFk-) translocation [10]. However, since TNF- and IL-1 have independent post-translational regulation mechanisms and endogenous inhibitors, these could account for differences in serum cytokine concentrations [42?5]. Therefore, treatment regimens targeted at reducing specific pro-inflammatory mediators involved in local inflammation in SCD may be useful in the management of sickle leg ulcers. The involvement of the pro-inflammatory cytokines IL-1 and TNF- in promoting endothelial adhesiveness, leukocyte activation [46] and the coagulation cascade [47] could render them potent mediators of episodic vasoocclusion in sickle cell disease and in promoting chronic leg ulcers. The properties of whole blood are such that changes in the whole blood viscosity have an inverse effect on the rate of blood flow. In vitro, this has important implications as normal blood flow can always be interrupted by any or a combination of factors which affect 1527786 either shear rate or viscosity. In sickle cell blood, the abnormal rheological properties conferred by the polymerization dependent rigidification of the erythrocyte membrane are worsened by small increments in WBV. Cooperative vasoocclusion may result from clumping of rigid red cells and leucocytes and their adherence to the activated endothelium. The greater concentrations of sICAM-1, IL-1, as wells as the raised WBV in SSu compared with SSn subjects may be indicative of inflammatory mediated vaso-occlusion in the pathogenesis of sickle cell leg ulcers. While it is conceivable how the up-regulation of adhesion factors may adversely affect WBV in vivo, it is unclear how these associations may be relevant in vitro since there is no endothelium for RBC adherence. The present findings showed increased mean cell size in the ulcer group compared with HbSS controls. Meanwhile, RDW was similar between groups, suggestive of similar cell densities and therefore unlikely to be associated with the higher WBV in the ulcer patients. Acute phase increases in certain proteins with attendant decrease in haematocrit have been reported in diabetic foot ulcers [48] and arteriosclerosis obliterans [49]. Further investigations into the association between acute phase proteins and plasma viscosity among these ulcer patients may aid in explaining our WBV findings. It is possible that a significantly greater mean cell volume, although within normal limits, could be associated with greater WBV in patients with ulcers compared with those without ulcers. A lower HVR or otherwise termed `erythrocyte transport effectiveness’ [50,51] [31] describes the rheological potential of the blood and therefore serves an index for assessing the likelihood of oxygen reaching tissues in the microcirculation for a given haematocrit and WBV. However, oxygen delivery is a complex process and is ultimately determined by several other factors including pH, temperature and red cell 2,3-diphosphoglycerate concentration. The viscosity recordings in the present work were lower than reported for normal or sickle blood [28,31]. The lower values may be due to a systematic error in the cone-plate viscometer used in our study. There are no reports in the literature regarding the involvement of body mass index (BMI) in sickle leg ulceration.Inflammation and Adhesion in Chronic Leg UlcersHowever, we reported a significantly greater BMI in patients with ulcers than those without ulcers which was related a significantly great.
