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Abstract

A life-threatening intoxication, requiring ventilatory support, is reported from the ingestion of 3.05?g of buflomedil, a peripheral vasodilator. Buflomedil at a dosage of 50?mg/kg weight produces seizures. Hypotension is not a specific symptom of intoxication. Buflomedil poisoning can be easily confused with other drugs, especially tricyclic antidepressants.     

GPI-PLD抗实验性大鼠动脉粥样硬化形成的初步研究

目的:探讨糖基化磷脂酰肌醇特异性磷脂酶(GPI-PLD)对实验性动脉粥样硬化大鼠血脂水平及血管功能、形态的影响。方法:雄性大鼠随机分为三组,静脉输入生理盐水对照组、高表达GPI-PLD(+)细胞组和GPI-PLD(-)细胞组。高脂喂养与维生素D注射(60万IU/kg)建立大鼠动脉粥样硬化模型。实验第6周末,检测血脂水平(总胆固醇,甘油三酯,低密度脂蛋白、高密度脂蛋白)和血清GPI-PLD活性,观察主动脉病理形态学,检测主动脉对乙酰胆碱诱导的内皮依赖性舒张反应。结果:与生理盐水对照组、GPI-PLD(-)细胞组比较,输入高表达GPI-PLD(+)细胞组大鼠的血GPI-PLD活性增加,总胆固醇、甘油三酯、低密度脂蛋白量减少,而高密度脂蛋白增多(P<0.01);动脉内皮细胞较完整,血管增厚程度明显减轻,泡沫细胞数量明显减少;结论:GPI-PLD可抑制高脂喂养大鼠动脉粥样硬化形成。     

硝普钠溶液配置后不同时间段的稳定性

目的 探讨硝普钠溶液的稳定性和临床上硝普钠溶液配置后的使用时限。方法 对不同时间段避光条件下的不同浓度、酸碱度、温度的硝普钠溶液,用电位滴定法测定其硝普钠药物含量,用氰化物检查法测定其降解产物氰化物的含量。结果 0．005％～0．02％浓度的硝普钠溶液在pH5．0～7．0、温度10℃～25℃时及常规的避光条件下,配制后24小时内是稳定的,其氰化物含量及硝普钠药物含量均符合要求。结论 硝普钠溶液在一定的pH、温度及合适的避光条件下,在体外比较稳定,使用时间适当延长是可行的。     

血管扩张药在急性心力衰竭中的应用

应用血管扩张药治疗急性心力衰竭(AHF)可改善血流动力学和临床症状,但血管扩张剂的临床效果尚未获得前瞻性大规模随机安慰剂对照临床研究验证.本文主要综述硝普钠和奈西立肽等常用血管扩张药在AHF治疗中的地位,并关注其临床应用的最佳指征以及可能导致的不良反应.     

Role of vasodilator stimulated phosphoprotein in VEGF induced blood–brain barrier permeability in endothelial cell monolayers

The blood–brain barrier (BBB) plays an important role in the pathophysiology of central nervous system (CNS) disorders such as stroke and hypoxic–ischemic brain injury. Vascular endothelial growth factor (VEGF) is involved in angiogenesis and vasogenic edema during stroke and hypoxia. However, the role of VEGF in BBB permeability after hypoxia has not been fully elucidated. We therefore investigated VEGF effects in an in vitro BBB model using rbcec4 endothelial cell line with the stimulation of VEGF or hypoxia. In this study, BBB permeability was studied using ¹⁴C-sucrose detection. The expression of BBB tight junction protein ZO-1, and the expression and phosphorylation of vasodilator stimulated phosphoprotein (VASP), VEGF and VEGF receptor 2 (VEGFR2) were determined using fluorescent immunocytochemistry and western blot analyses. We found that hypoxia upregulated VEGF expression, and VEGF increased BBB permeability. Hypoxia also increased VASP phosphorylation, which was mediated, in part, through VEGFR2. We also found that VASP at tight junctions was co-localized with ZO-1 in cell–cell contacts. Our findings show that VASP phosphorylation is affected by hypoxia and VEGFR2 inhibition suggesting a role for VASP in BBB permeability.     

Tributyltin induces disruption of microfilament in HL7702 cells via MAPK‐mediated hyperphosphorylation of VASP

Tributyltin (TBT) has been widely used for various industrial purposes, and it has toxic effects on multiple organs and tissues. Previous studies have found that TBT could induce cytoskeletal disruption, especially of the actin filaments. However, the underlying mechanisms remain unclear. The aim of the present study was to determine whether TBT could induce microfilament disruption using HL7702 cells and then to assess for the total levels of various microfilament‐associated proteins; finally, the involvement of the MAPK pathway was investigated. The results showed that after TBT treatment, F‐actin began to depolymerize and lost its characteristic filamentous structure. The protein levels of Ezrin and Cofilin remained unchanged, the actin‐related protein (ARP) 2/3 levels decreased slightly, and the vasodilator‐stimulated phosphoprotein (VASP) decreased dramatically. However, the phosphorylation levels of VASP increased 2.5‐fold, and the ratio of phosphorylated‐VASP/unphosphorylated‐VASP increased 31‐fold. The mitogen‐activated protein kinases (MAPKs) ERK and JNK were discovered to be activated. Inhibition of ERK and JNK not only largely diminished the TBT‐induced hyperphosphorylation of VASP but also recovered the cellular morphology and rescued the cells from death. In summary, this study demonstrates that TBT‐induced disruption of actin filaments is caused by the hyperphosphorylation of VASP through MAPK pathways. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1530–1538, 2016.     

The RegEx trial: a randomized, double-blind, placebo- and active-controlled pilot study combining regadenoson, a selective A2A adenosine agonist, with low-level exercise, in patients undergoing myocardial perfusion imaging

Background  Although vasodilator stress myocardial perfusion imaging (MPI) is increasingly performed with exercise, adenosine A_2A receptor agonists have not been studied with exercise. Objectives  To determine the safety of administering regadenoson during exercise and, secondarily, to evaluate image quality, patient acceptance, and detection of perfusion defects. Methods  Patients requiring pharmacologic MPI received a standard adenosine-supine protocol (AdenoSup, n = 60) and were then randomized (2:1) in a double-blind manner to low-level exercise with bolus intravenous injection of regadenoson (RegEx, n = 39) or placebo (PlcEx, n = 21). Results  Adverse events occurred in 95%, 77%, and 33% of patients receiving AdenoSup, RegEx, and PlcEx, respectively. Peak heart rate was 13 beats per minute (bpm) and 21 bpm greater following RegEx compared to that following PlcEx and AdenoSup, respectively (P = .006 and <.001). Change from baseline in mean systolic blood pressure (SBP), change from baseline to nadir SBP, and percentage of patients with a decline in SBP by ≥20 mm Hg showed no important differences between RegEx and PlcEx. No occurrences of 2nd degree or higher AV block were observed following RegEx or PlcEx; one patient developed 2nd degree AV block following AdenoSup. The mean heart-to-liver and heart-to-gut ratios were improved on RegEx vs AdenoSup: 0.85 (0.34) vs 0.65 (0.26), P < .001 and 1.1 (0.36) vs 0.97 (0.34), P < .001, respectively. Compared to AdenoSup, 70% of patients felt RegEx was much or somewhat better. Conclusions  Combining regadenoson with low-level exercise is feasible, well tolerated, and associated with fewer side effects compared to AdenoSup. Presented, in part, at American College of Cardiology 56th Annual Scientific Session, New Orleans LA, March 25, 2007.     

The effect of beta-blockers on the diagnostic accuracy of vasodilator pharmacologic SPECT myocardial perfusion imaging

Background  The effect of beta (β) blockers on the accuracy, particularly the sensitivity, of vasodilator radionuclide myocardial perfusion imaging (MPI) is not entirely clear. This study aimed to further assess the effect of β-blockers on the ability of MPI to identify significant and high-risk coronary artery disease (CAD). Methods and Results  For 555 patients who underwent vasodilator MPI and had coronary angiography within 90 days, global and per-vessel sensitivities and specificities were calculated, and were found to be similar between patients taking β-blockers and those who were not. β-blockers did not decrease the ability to detect patients with multivessel disease. Summed stress scores and summed rest scores were likewise similar in both groups. To account in part for catheterization referral bias and the potential of false-negative MPI studies in patients receiving β-blockers, survival analysis was performed on 2646 patients with normal MPI studies who did not undergo cardiac catheterization and failed to demonstrate significant mortality difference related to the taking of β-blockers. Conclusions  β-blocker therapy does not diminish the ability of vasodilator stress MPI to detect clinically significant CAD, nor hide the mortality risk of patients with normal studies not referred for catheterization. Presented in part at the American Society of Nuclear Cardiology 9th Scientific Session, September 2004, New York, NY.     

Systemic levels following PGE1 inhalation in neonatal hypoxemic respiratory failure

AIM: To measure plasma prostaglandin E1 (PGE1) levels in newborns with hypoxemic respiratory failure (NHRF) following inhaled PGE1 (IPGE1), normal term newborns, and newborns with congenital heart disease (CHD) following intravenous PGE1. METHODS: Twenty newborns with NHRF received IPGE1 by jet nebulizer in doses of 25, 50, 150, and 300 ng/kg/min followed by weaning. Blood for PGE1 assay using enzyme immunoassay was available in eight neonates with NHRF, 10 normal newborns, and three neonates with CHD. RESULTS: There were no differences in PGE1 levels between cord arterial blood in normal newborns and baseline samples from newborns with NHRF. Oxygenation improved significantly following IPGE1 (p=0.024) in newborns with NHRF. No adverse events were identified. Although a reversible increase in PGE1 levels was detected following a dose of 50 ng/kg/min (p<0.05), there was no association between PGE1 levels and IPGE1 duration, PaO2, temperature, heart rate, and blood pressure. CONCLUSION: A reversible increase in mean PGE1 levels was demonstrable at low doses of IPGE1 in babies with NHRF using a sensitive assay, suggesting effective drug delivery. Levels did not increase further with increasing dose or duration of administration, suggesting local action in the lungs and a lack of systemic spillover due to extensive pulmonary metabolism offering pulmonary selectivity.