Platelet adhesion to collagen types I through VIII under conditions of stasis and flow is mediated by GPIa/IIa (alpha 2 beta 1-integrin)

Platelet adhesion to fibrillar collagens (types I, II, III, and V) and nonfibrillar collagens (types IV, VI, VII, and VIII) was investigated in the presence of physiologic concentrations of divalent cations under conditions of stasis and flow. Under static conditions, platelet adhesion was observed to collagen types I through VII but not to type VIII. Under flow conditions, platelet adhesion to collagen types I, II, III, and IV was almost independent of shear rates above 300/s. Collagen type V was nonadhesive. Platelet adhesion to collagen type VI was shear rate-dependent and optimal at a rate of 300/s. Collagen types VII and VIII showed minor reactivity and supported platelet adhesion only between shear rates 100 to 1,000/s. Monoclonal antibody (MoAb) 176D7, directed against platelet membrane glycoprotein Ia (GPIa; very late antigen [VLA]-alpha 2 subunit), completely inhibited platelet adhesion to all collagens tested, under conditions of both stasis and flow. Platelet adhesion to collagen type III at shear rate 1,600/s was only inhibited for 85%. The concentration of antibody required for complete inhibition of platelet adhesion was dependent on the shear rate and the reactivity of the collagen. An MoAb directed against GPIIa (VLA-beta subunit) partially inhibited platelet adhesion to collagen. These results show that GPIa-IIa is a major and universal platelet receptor for eight unique types of collagen.     

Platelet turnover and kinetics in immune thrombocytopenic purpura: results with autologous 111In-labeled platelets and homologous 51Cr- labeled platelets differ

Mean platelet survival and turnover were simultaneously determined with autologous 111In-labeled platelets (111In-AP) and homologous 51Cr- labeled platelets (51Cr-HP) in ten patients with chronic immune thrombocytopenic purpura (ITP). In vivo redistribution of the 111In-AP was quantitated with a scintillation camera and computer-assisted image analysis. The patients were divided into two groups: those with splenic platelet sequestration (spleen-liver 111In activity ratio greater than 1.4), and those with diffuse sequestration in the reticuloendothelial system. The latter patients had more severe ITP reflected by pronounced thrombocytopenia, decreased platelet turnover, and prominent early hepatic platelet sequestration. Mean platelet life span estimated with 51Cr-HP was consistently shorter than that of 111In-AP. Platelet turnover determined with 51Cr-HP was thus over-estimated. The difference in results with the two isotope labels was apparently due to greater in vivo elution of 51Cr. Although the limitations of the techniques should be taken into account, these findings indicate that platelet turnover is not always normal or increased in ITP, but is low in severe disease. We suggest that this may be ascribed to damage to megakaryocytes by antiplatelet antibody. The physical characteristics in 111In clearly make this radionuclide superior to 51Cr for the study of platelet kinetics in ITP.     

Direct medical costs of adverse events in Dutch hospitals

Background  

Up to now, costs attributable to adverse events (AEs) and preventable AEs in the Netherlands were unknown. We assessed the total direct medical costs associated with AEs and preventable AEs in Dutch hospitals to gain insight in opportunities for cost savings.     

一种用于筛选降血糖及降血脂药物的动物模型

一种用于筛选降血糖及降血脂药物的动物模型刘京，申竹芳，刘海帆，叶菲，谢明智（中国医学科学院药物研究所，中国协和医科大学北京１０００５０）糖尿病为常见病和多发病，同时伴有多方面的并发症，脂质代谢紊乱即其中之一。这就要求治疗糖尿病时，除控制病人的血糖外，...     

FC04.6Characterisation of dendritic cell responses to ascaridol, an autoxidation product of tea tree oil

A large number of monoterpenes and their degradation products are likely skin sensitizing agents (Hausen et al., 1999). Terpenes are very common e.g., as constituents of cosmetics, food and other daily used products.
We investigated responses to the endoperoxide 1,4‐epidioxy‐2‐p‐menthen (ascaridol), an autoxidation product of tea tree oil, using monocyte derived dendritic cells (MDDC). Therefore, we isolated peripheral blood mononuclear cells (PBMC) from 9 healthy donors by the standard Ficoll‐Paque gradient centrifugation.
Monocytes were isolated by adherence and incubated in media (RPMI 1640) containing GM‐CSF (800 units/ml), IL‐4 (1000 units/ml) and 10% autologous serum. The immature MDDC (day 6) were characterized by flow cytometry (CD1a+, CD14−, CD40, CD45, CD80, CD83, CD86, HLA‐DR and CCR‐7) and incubated with various concentrations of ascaridol (1–70 μg/ml). After one hour incubation time LPS was added (1 μg/ml) for 23 h. Cell culture supernatants were collected after 24 h for cytokine analysis.
IL‐12p40, IL‐12p70 and prostaglandin E2 were measured by ELISA, TNF‐alpha and IL‐2 were measured by flow cytometry (FACS). Methods of the quantification of steady state mRNA levels were established for IL‐12 and CCR7 (real‐time RT‐PCR). Ascaridol enhanced significantly IL‐12p70 production (120% up to 396%) by MDDC as well as mRNA levels for IL‐12 and CCR7. Moreover, we detected a distinct increase of TNF‐alpha (110% up to 146%) secretion, IL‐2 (135%) and PGE2 (102% up to 155%).
Totally, these results suggest that ascaridol may be a potent modulator of maturation and antigen presenting function of dendritic cells, and we performing further experiments to verify this hypothesis.
This study was supported by the Deutsche Forschungsgemeinschaft.