No abstract

The aim of our study was to assess the cytokine profile of sickle cell disease (SCD) patients in steady state and in vaso-occlusive crisis (VOC). VOC has a complex nature, involving interactions between sickle red blood cells (RBC), the endothelium, and leucocytes. Endothelial damage due to recurrent adhesion of sickle RBCs may disrupt endothelial function, leading to altered cytokine release. It is therefore pertinent to study the cytokine profile of SCD patients in steady state and in crisis prior to exploring its contribution to vasoocclusive manifestations, since it is believed that an altered balance of proinflammatory and anti-inflammatory cytokines plays an important role in painful crisis. Cytokines including IL1b, IL-2, IL-4, IL-6, IL-8, TNF-a, and IFN-g were measured by commercially available ELISA kits in SCD patients (n = 60); in steady state (n = 26) and in painful crisis (n = 34) and compared with nonanemic age-and sex-matched normal Omani controls (n = 20). SCD patients in crisis showed elevated levels of TNF-a (P < 0.092) and IL-6 (P < 0.024) when compared with steady state. It was also observed that SCD patients in steady state showed a significant elevation in IL-1b (P < 0.04), IL-6 (P < 0.0001), and IFN-g (P < 0.02) as compared to normal subjects. It is thus evident that both type I and type II cytokines are significantly altered in SCD patients. In steady state, type II proinflammatory cytokines are elevated, whereas in crisis, an additional augmentation of type I cytokines occurs, with persistent elevation of type II cytokines, emphasizing the role of perturbed endothelium and activated monocytes in the pathophysiology of vaso-occlusion in sickle cell crisis. Am.

Regeneration of periodontal tissues requires orchestration of several cell types. Two cell types, gingival fibroblastic cells (gingival fibroblasts) and cells from the periodontal ligament (PDL cells), were studied to compare the effects of supplemental addition of TGF-beta 1 and PDGF on proliferation. Cells obtained from healthy donors were cultured in 10% FBS supplemented with either 10 ng/ml TGF-beta 1, 20 ng/ml PDGF, or both. Thymidine incorporation was measured after 24, 48, or 72 hours. Data from PDL (analyzed by ANOVA) showed the following relations: at 24 hours TGF beta 1/PDGF = PDGF > TGF-beta 1 = control; at 48 hours TGF beta 1/PDGF > TGF-beta 1 > PDGF > control; at 72 hours TGF beta 1/PDGF > TGF-beta 1 > PDGF = control. Gingival fibroblast cultures showed the following relations: at 24 and 48 hours TGF beta 1/PDGF = PDGF > TGF-beta 1 = control; at 72 hours, TGF beta 1/PDGF = PDGF > control with TGF beta 1 not different from control or factor combinations. Both TGF-beta 1 and TGF-beta 1/PDGF showed a significantly greater increase in proliferation of PDL cells than in gingival fibroblasts at 48 and 72 hours (Student t test P < 0.05). In contrast, PDGF stimulated proliferation of gingival fibroblasts was significantly greater than PDL cells at 72 hours (P < 0.05). Thus, supplementation of complete cultures (containing 10% FBS) with TGF-beta 1 alone or combined with PDGF stimulates proliferation of PDL cells to a significantly greater extent than proliferation of gingival fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship between implant surfaces and decontamination treatments was studied in vitro to determine which implant surfaces were most effectively decontaminated, and which treatment was most effective for treating a particular implant surface. The implants used in the study were press fit cylindrical titanium units with machined, plasma sprayed, and hydroxyapatite-coated surfaces. Radioactive endotoxin (125I-LPS) was prepared from Porphyromonas gingivalis (ATCC 33277). Implants were coated with 125I-LPS and treated by burnishing with a cotton pellet soaked in water, citric acid solution (CA), or 0.12% chlorhexidine (CHX); or treated with an air-powder abrasive (AIR). Radioactivity was determined after each of two treatment cycles. The results for each implant surface were analyzed using ANOVA to determine differences between treatments. The remaining 125I-LPS after two treatment cycles were: for machined implants AIR < CA, with AIR = water = CHX and water = CHX = CA; for plasma sprayed implants AIR < water = CHX = CA; for hydroxyapatite implants AIR = CA < water < CHX. In evaluating treatment modalities, it was found that machined implants were decontaminated more effectively than the other surfaces by all treatments; the exception was citric acid treatment which was equally effective on either machined or hydroxyapatite surfaces. These results indicate that machined implants (without surface coating) are most readily decontaminated by a variety of methods; this characteristic should be considered, since long-term success of implants may involve treating periimplantitis. Further, the results indicate that air abrasives are effective for decontaminating implant surface, with the exception that hydroxyapatite coated surfaces can be treated equally with air abrasives or citric acid.

Sickle red cells express adhesion molecules including integrin alpha4beta1, CD36, band 3 protein, sulfated glycolipid, Lutheran protein, phosphatidylserine and integrin-associated protein. The proadhesive sickle cells may bind to endothelial cell P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), CD36 and integrins leading to its activation. Monocytes also activate endothelium by releasing proinflammatory cytokines like tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta). Sickle monocytes also express increased surface CD11b and cytoplasmic cytokines TNFalpha and IL-1beta indicating activated state. Polymorphonuclear leukocytes (PMNs) are also activated with reduced L-selectin expression, enhanced CD64 expression and elevated levels of sL-selectin, sCD16 and elastase resulting in increased adhesiveness to the endothelium. Platelets are also activated and secrete thrombospondin (TSP) and cytokine IL-1. They also form platelet- monocytes aggregates causing endothelial cell P-selectin expression. Endothelial cell activation by these multiple mechanisms leads to a loss of vascular integrity, expression of leukocyte adhesion molecules, change in the surface phenotype from antithrombotic to prothrombotic, excessive cytokine production and upregulation of HLA molecules. Furthermore, contraction of these activated endothelial cells leads to exposure of extracellular matrix proteins, such as TSP, laminin, and fibronectin and their participation in adhesive interactions with bridging molecules from the plasma such as von Willebrand factor (vWf) released from endothelial cells, ultimately culminating in vasoocclusion and local tissue ischemia, the pathognomonic basis of vasoocclusive crisis.