Characterization of erythrocyte quality during the refrigerated storage of whole blood containing di-(2-ethylhexyl) phthalate

Di-(2-ethylhexyl) phthalate (DEHP) accumulates in blood brought into contact with materials utilizing this compound as a plasticizer. To determine whether this phthalate diester affects red blood cell integrity, we have compared cell morphology, plasma hemoglobin accumulation, micro-vesicle production, and the concentration of intracellular metabolites and electrolytes of erythrocytes from blood stored at 4 degrees C with and without DEHP. When sufficient emulsified DEHP was mixed with blood to give a final concentration of 300 micrograms/mL, plasma hemoglobin accumulation was reduced by an average of 70%, the percentage of cells exhibiting normal morphology was enhanced by at least 20-fold, and the volume of microvesicles released from red blood cells was reduced by 50% after 35 days of refrigerated storage compared to the values obtained from corresponding samples stored without added phthalate. Similar effects were observed regardless of whether blood was stored in nonplasticized polypropylene or tri-(2-ethylhexyl) trimellitate plasticized polyvinylchloride containers and with DEHP solubilized by a variety of emulsifiers. When 300 micrograms/mL DEHP was added to stored blood containing erythrocytes predominantly in the echinocyte conformation, many of the cells reverted to the normal discoid morphology. The addition of this quantity of DEHP to blood had no significant effect on the course of storage-induced changes in erythrocyte adenosine triphosphate (ATP), 2,3-diphosphoglycerate (2,3-DPG), sodium or potassium concentrations. The data are consistent with the hypothesis that DEHP inhibits the deterioration of the red blood cell membrane that results from the refrigerated storage of whole blood.     

Direct and indirect costs of tuberculosis among immigrant patients in the Netherlands

Background  

In low tuberculosis (TB) incidence countries TB affects mostly immigrants in the productive age group. Little empirical information is available about direct and indirect TB-related costs that patients face in these high-income countries. We assessed the direct and indirect costs of immigrants with TB in the Netherlands.     

Difficult mammographic needle localizations: use of alternate orthogonal projections

Lesions deep within the breast are occasionally visible on only one standard mammographic projection and are therefore difficult to localize preoperatively. Such abnormalities can often be visualized on two orthogonal 45 degrees oblique views. In these cases, needle localizations may be performed in a routine manner without computed tomography or stereotactic methods.     

Laparoscopic repair of a strangulated Bochdalek hernia

Background Bochdalek herniae are rare. They are usually repaired by open abdominal surgery or by a thoracic video-assisted approach. When strangulated and in a compromised patient the options are fewer. Aim To describe a case treated by a laparoscopic approach. Results The procedure was technically difficult, but the patient recovered without recurrence. Conclusion Laparoscopic repair is possible even with strangulation.     

1 282名驾驶员焦虑水平与危险驾驶关系研究

[摘要] 目的 探讨驾驶员焦虑水平对危险驾驶行为的关系。方法 采用问卷调查法,分别使用贝克焦虑量表与 Dula危险驾驶行为量表( DDDI-Dula Dangerous Driving Index)对1285名驾驶员的焦虑水平与危险驾驶行为进行了评价。此外,研究分析两者之间的相关性,对不同焦虑水平驾驶员的危险行为进行方差分析。 结果 （1）焦虑总分与危险驾驶量表总分呈显著性正相关（p<.01）,焦虑总分与危险驾驶量表的三个子量表分数均呈显著性正相关（p<.01）。（2）由F检验知,处于不同焦虑水平的驾驶员其危险驾驶行为在以下方面存在不同（p<.05）：DDDI总分,过去6个月的驾驶肇事次数,过去两个周 "尾随"行为的次数,过去两周内超速的次数,过去两周内超速驶入应停车减速的区域的次数,过去四周影响下驾驶行为的次数。结论 驾驶员的焦虑水平可以影响危险驾驶行为,高的焦虑水平与更多的危险驾驶行为显著相关。     

Increased platelet aggregation due to chilling to 20 degrees C is not related to increased sensitivity to agonists

BACKGROUND: Previous studies suggested that chilled platelets have a greater sensitivity to agonists than do platelets aggregated at 37 degrees C. STUDY DESIGN AND METHODS: Washed platelets were aggregated at 20 or 37 degrees C with ADP (0-20 microM), arachidonic acid (0-200 microM), or the thromboxane mimetic U46619 (0-9 nM). RESULTS: Chilling caused a significant (p < or = 0.05) increase in spontaneous platelet aggregation (> 27% at 20 degrees C vs < 5% at 37 degrees C) and spontaneous dense granule release (> 0.01 nM of ATP at 20 degrees C vs. 0 nM of ATP at 37 degrees C), ADP and U46619 caused a significantly greater aggregation response and dense granule release at 20 degrees C, although there was no change in agonist sensitivity of platelets (effective dose of agonist necessary to induce 50% aggregation [ED50]: 1.00 +/− 0.35 microM ADP at 20 degrees C and 1.63 +/− 0.47 microM ADP at 37 degrees C; 8.26 +/− 3.65 pM U46619 at 20 degrees C and 18.97 +/− 4.82 pM U46619 at 37 degrees C). Platelets aggregated with arachidonic acid showed a significant decrease in aggregation and agonist sensitivity at 20 degrees C (ED50 118.7 +/− 44.4 microM) from those at 37 degrees C (ED50 25.6 +/− 7.2 microM), possibly as a result of the reduced enzymatic activity of cyclooxygenase and thromboxane synthase at the lower temperature. CONCLUSION: The data suggested that washed platelets chilled to 20 degrees C and aggregated are not more sensitive to agonists than are 37 degrees C controls, but rather that chilled platelets undergo greater spontaneous aggregation.     

Novel pyrazole compounds for pharmacological discrimination between receptor-operated and store-operated Ca2+ entry pathways

Background and purpose

Pyrazole derivatives have recently been suggested as selective blockers of transient receptor potential cation (TRPC) channels but their ability to distinguish between the TRPC and Orai pore complexes is ill-defined. This study was designed to characterize a series of pyrazole derivatives in terms of TRPC/Orai selectivity and to delineate consequences of selective suppression of these pathways for mast cell activation.

Experimental approach

Pyrazoles were generated by microwave-assisted synthesis and tested for effects on Ca²⁺ entry by Fura-2 imaging and membrane currents by patch-clamp recording. Experiments were performed in HEK293 cells overexpressing TRPC3 and in RBL-2H3 mast cells, which express classical store-operated Ca²⁺ entry mediated by Orai channels. The consequences of inhibitory effects on Ca²⁺ signalling in RBL-2H3 cells were investigated at the level of both degranulation and nuclear factor of activated T-cells activation.

Key Results

Pyr3, a previously suggested selective inhibitor of TRPC3, inhibited Orai1- and TRPC3-mediated Ca²⁺ entry and currents as well as mast cell activation with similar potency. By contrast, Pyr6 exhibited a 37-fold higher potency to inhibit Orai1-mediated Ca²⁺ entry as compared with TRPC3-mediated Ca²⁺ entry and potently suppressed mast cell activation. The novel pyrazole Pyr10 displayed substantial selectivity for TRPC3-mediated responses (18-fold) and the selective block of TRPC3 channels by Pyr10 barely affected mast cell activation.

Conclusions and Implications

The pyrazole derivatives Pyr6 and Pyr10 are able to distinguish between TRPC and Orai-mediated Ca²⁺ entry and may serve as useful tools for the analysis of cellular functions of the underlying Ca²⁺ channels.