Vanilloid-like agents inhibit aggregation of human platelets

Introduction

Plant-derived and endogenous vanilloid-like agents exert their effects on cells through transient receptor potential vanilloid-1 (TRPV1). Little is known about the effects of these agents on platelet aggregation. We investigated the effect of various vanilloid-like agents on in-vitro platelet aggregation and tested whether this action is mediated through TRPV1. Understanding the mechanism of action of these compounds in platelets is important in that these compounds may be developed as novel anti-platelet agents.

Materials and Methods

The effects of plant-derived (capsaicin; dihydrocapsaicin, DHC) and endogenous vanilloid-like agents (N-oleoyldopamine, OLDA; N-arachidonoyl-dopamine, NADA) on platelet aggregation were investigated using ADP (5, 10 μM), collagen (4, 8 μg/mL) and arachidonic acid (AA, 300, 400 μg/mL) as agonists. The direct effects of these agents on platelet viability were also determined using an LDH release assay.

Results

Capsaicin, OLDA and NADA inhibited ADP-induced platelet aggregation in a concentration-dependent manner. OLDA and NADA, but not capsaicin and DHC, inhibited collagen-induced aggregation, whereas AA-induced aggregation was inhibited by capsaicin, DHC and NADA, but not OLDA. Inhibition of aggregation was not due to direct toxicity of these agents towards platelets. The TRPV1 antagonist, SB-452533, did not affect inhibition of ADP-induced platelet aggregation by capsaicin and OLDA.

Conclusions

These results demonstrate that the endovanilloids, OLDA and NADA, and plant-derived vanilloid, capsaicin, inhibit ADP-induced platelet aggregation. Collagen-induced aggregation was inhibited only by endovanilloids, whereas AA-induced aggregation was inhibited by capsaicin, DHC and NADA. This inhibition was not due to direct toxic effects of these agents, nor was inhibition of ADP-induced aggregation TRPV1 mediated.     

A Computerized Order Entry System Was Adopted with High User Satisfaction at an Orthopedic Teaching Hospital

Background

Computerized provider order entry (CPOE) has been considered essential for the reduction of medical errors and increased patient safety. Assessment of staff perception regarding a CPOE system is important for satisfaction and adoption. Incorporation of user feedback can greatly improve the functionality of a system and promote user satisfaction.

Questions/Purposes

This study aims to develop an informatics staff satisfaction survey instrument and to understand what components of computerized prescriber order entry (CPOE) contribute to staff satisfaction and its variability over time.

Methods

The 22-question survey was developed by a multidisciplinary group and focused on patient data including demographics, orders, medications, laboratory, and radiology data. The questions were designed to understand if clinicians (1) could easily access the information needed to properly take care of patients, (2) could act upon the information once acquired, (3) could obtain the information clearly, and (4) were alerted to potential errors. The survey was distributed just prior to “go-live,” 6 and 12 months after go-live. Responses were given on a five-point Likert scale.

Results

The survey results post-implementation showed user satisfaction with CPOE. Satisfaction regarding the ease of obtaining orders, medication, and lab data had a significant improvement at 6 and 12 months post-implementation, p < 0.001. Satisfaction that the computerized order entry system provided information needed to take care of their patients improved, p < 0.01. At 1 year post-implementation, user satisfaction declined from 6 months earlier but still demonstrated an overall increase in satisfaction from pre-implementation.

Conclusion

Compared prior to go-live, clinicians are satisfied or very satisfied across multiple spheres and multiple disciplines. At all time points, clinicians were able to obtain information required to take care of their patients. However, post-go-live, it was easier to obtain and act upon as well as more clear and understandable.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-013-9377-1) contains supplementary material, which is available to authorized users.     

瞬时受体电位通道A1和瞬时受体电位通道M8在冷过敏中的作用

背景 冷过敏是炎性痛和神经病理性疼痛的一个常见症状,其内在机制尚不清楚. 目的 阐明瞬时受体电位通道A1 （transient receptor potential cation channel,subfamily A,member 1,TRPA1）和瞬时受体电位通道M8（transient receptor potential melastatin 8,TRPM8）参与冷过敏的机制. 内容 综述TRPA1和TRPM8的分子结构和门控机制及其在有害的冷、炎性痛和神经病理性疼痛的冷过敏形成、维持中的作用等方面的研究. 趋向 深入研究TRPA1和TRPM8在冷过敏发生中的作用,有助于阐明冷过敏的机制,并为开发拮抗剂提供理论依据.     

Combined remote ischemic perconditioning and local postconditioning on liver ischemia–reperfusion injury

Background

Remote ischemic perconditioning (rPER) is the newest technique described to mitigate ischemia and reperfusion (IR) injury. Local postconditioning (POS) is also an effective technique for this purpose. It is uncertain if adding local POS to rPER provides superior liver protection, so we tested this hypothesis.

Materials and methods

Twenty five Wistar rats were assigned into five groups: sham, IR, POS, rPER, and rPER + POS. Animals were subjected to liver ischemia for 60 min. POS consisted of four cycles of 5-min liver perfusion followed by 5-min liver ischemia (40 min total) after the major ischemic period. rPER consisted of four cycles of 5-min hindlimb ischemia followed by 5 min hindlimb perfusion contemporaneously to major liver ischemic period, during its last 40 min. After 2 h, median and left lobes were harvested for malondialdehyde and Trolox equivalent antioxidant capacity (TEAC) measurement, and blood for the measurement of serum transaminases.

Results

All tissue conditioning techniques were able to reduce transaminases serum levels, having no differences among them. All tissue conditioning techniques were able to reduce hepatic tissue MDA level; however, only rPER + POS had higher values than SHAM. All tissue conditioning techniques also enhanced TEAC; however, only POS had lower TEAC than SHAM.

Conclusions

rPER appears as the most promising technique to avoid IR injury. This technique reduced oxidative stress of cell membranes and lowered transaminases serum level. There was no additive protection when POS and rPER were held together.     

Delayed remote preconditioning induces cardioprotection: role of heme oxygenase-1

Background

The role of heme oxygenase-1 (HO-1) in the cardioprotection induced by delayed remote ischemic preconditioning (DRIPC) has not been investigated. Therefore, this study was designed to investigate whether HO-1 is involved in DRIPC-mediated cardioprotection in an isolated perfused rat heart model.

Materials and methods

Isolated rat hearts were subjected to 30 min ischemia followed by 60 min reperfusion. DRIPC (four cycles 5-min occlusion and 5-min reflow at the unilateral hind limb once per day for 1, 2, or 3 d before heart isolation, abbreviated as D1RIPC, D2RIPC, or D3RIPC respectively). Infarct size, myocardial troponin levels, and heart function were measured. The protein and messenger RNA levels of HO-1 were determined.

Results

DRIPC facilitated postischemic cardiac functional recovery and decreased cardiac enzyme release. The infarct size-limiting effect of DRIPC was more pronounced in the D3RIPC group (10.22 ± 2.57%) than the D1RIPC group (22.34 ± 4.02%, P < 0.001) or the D2RIPC group (14.60 ± 3.13%, P = 0.034). These effects in the D1RIPC group could be blocked by Zinc Protoporphyrin IX (ZnPP) (an HO-1 specific inhibitor). DRIPC-mediated cardioprotection was associated with enhanced HO-1 protein expression (D1RIPC, 0.11 ± 0.03; versus 0.15 ± 0.06 in the D2RIPC group, P = 0.06; versus 0.20 ± 0.04 in the D3RIPC group, P = 0.04) and messenger RNA levels of HO-1 expression.

Conclusions

Our findings suggest that HO-1 is involved in the cardioprotection induced by DRIPC, and that increase in the number of preconditioning stimuli may enhance cardioprotective effects accompanied with increased HO-1 level.