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.     

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.     

二氢吡啶类钙拮抗剂对钙调素依赖性环核苷酸磷酸二酯酶的抑制机理

用单克隆抗体纯化的60kd为亚基的牛脑钙调素依赖性环核苷酸磷酸二酯酶的动力学研究表明,二氢吡啶类钙拮抗剂Nicardipine和Felodipine是该酶的“部分”竞争性抑制剂。因为近饱和浓度的药物抑制该酶活性仅能达到某限定值,且Dixon作图法不呈直线关系。该酶被一定浓度Felo-dipine抑制时,增加Nicardipine浓度可逆转酶的抑制而达到Nicardipine的最大抑制水平,Nicardipine不影响典型的竞争性抑制剂甲基异丁基黄嘌呤对该酶的抑制作用,说明该酶活性中心以外存在和二氢吡啶结合的部位。