替罗非班在急性心肌梗死介入治疗中的疗效

目的:研究ST段抬高型急性心肌梗死(AMI)患者在急诊行经皮冠状动脉介入术(PCI)中应用替罗非班的有效性和安全性. 方法:患者80名,随机分为试验组(替罗非班+PCI组)40例,对照组(PCI组)40例.观察PCI术前、术后梗死相关动脉(IRA)TIMI血流情况以及患者7d内两组患者心血管事件(MACE)的发生率,及术后两组惠者的出血发生率. 结果:介入术后造影显示替罗非班组患者恢复TIMI 3级血流比例明显高于对照组.住院期间替罗非班组心血管事件发生率较对照组低(P<0.05).而两组间术后出血比例差异无统计学意义. 结论:ST段抬高型急性心肌梗死(AMI)患者在急诊冠状动脉介入术中使用血小板膜糖蛋白Ⅱb/Ⅲa受体拮抗剂替罗非班是有效并且安全的,其疗效优于常规治疗组.     

急性冠脉综合征患者介入应用替罗非班对冠脉血流和心肌灌注的影响

目的观察急性冠脉综合征患者介入治疗中应用替罗非班对冠脉血流的影响。方法接受经皮冠状动脉介入治疗(PCI)急性冠脉综合征患者共82例,分为替罗非班组42例(替罗非班+介入治疗),对照组40例(介入治疗),观察两组患者冠状动脉血流指标如TIMI血流分级、校正的TIMI计帧数(CTFC)、TIMI心肌灌注分级(TMPG)的差别。结果替罗非班组TIMI血流分级、TIMI计帧、TIMI灌注分级均明显优于对照组(P<0.05)。结论急性冠脉综合征患者介入治疗中应用替罗非班可以改善冠脉血流及心肌灌注。     

在急诊冠状动脉介入术中应用盐酸替罗非班的护理体会

报道了盐酸替罗非班在46例急性ST段抬高型心肌梗死(STEMI)患者急诊冠状动脉介入术(PCI)中的应用。46例患者术中、术后使用替罗非班,术后24h及30dMACE的发生率明显低于以往只用PCI的患者,并且提高了梗死相关血管(IRA)心肌灌注血流(TIMI),但使用替罗非班组的患者出血事件稍多。总之盐酸替罗非班应用于急诊PCI术治疗急性STEMI患者效果良好,可减少并发症的发生。     

术前与术中使用替罗非班对急性ST段抬高心肌梗死急诊介入治疗慢血流的比较及安全性

目的:探讨术前与术中应用替罗非班对急性ST段抬高心肌梗死经皮冠状动脉介入(PCI)治疗中慢血流的比较及安全性。方法:将90例急性ST段抬高心肌梗死患者随机分为替罗非班术前组(30例)、替罗非班术中组(30例)和对照组(30例)。比较三组患者梗死相关血管PCI治后即刻TIMI血流、校正TIMI帧数计数(CTFC)、90min ST段回落百分比、出血和血小板减少的发生率。结果:与对照组相比,替罗非班术前组及替罗非班术中组PCI后慢血流发生率显著降低(P<0.05),90min内ST段回落百分比提高;与替罗非班术中组相比,替罗非班术前组PCI后慢血流发生率降低更加显著(P<0.05);两组患者均未出现住院期间死亡及急性血栓形成,出血并发症比较差异无统计学意义(P>0.05)。结论:PCI术前早期应用替罗非班能更好地改善急性ST段抬高心肌梗死患者PCI后梗死相关血管的慢血流的发生,临床应用安全有效。     

直接冠脉内注射替罗非班在急性心肌梗死患者急诊PCI中治疗疗效的研究

目的探讨在急性心肌梗死(包括ST段抬高及非ST段抬高心肌梗死)患者行急诊PCI的过程中,冠脉内注射替罗非班继之静脉内持续泵入使用的安全性,以及能否进一步改善患者的急诊PCI疗效及减少术后近期心血管事件的发生率。方法回顾性分析2008年12月—2010年12月,37例急性心肌梗死患者行急诊PCI治疗时冠脉内注射了替罗非班继之静脉持续维持,另将同期的37例急性心肌梗死行急诊PCI时仅静脉内使用替罗非班的患者作为对照组,比较两组间的基础临床状况,术前术后梗死相关血管(IRA)的TIMI血栓积分(TIMI Thrombus Score)、TIMI血流分级(TIMI Flow Grades)、校正的TIMI血流帧数计数(Corrected TIMI Frame Count)、TIMI心肌灌注(TIMI Myocardial Perfusion)情况以及术后90 min心电图ST段回落百分比(sum-STR),以及住院期间主要心血管事件、出血事件及左室射血分数等。结果两者基础临床情况差异无显著性(P0.05),冠脉内注射替罗非班继之静脉维持组术后达到TMP分级2级以上获得率(分别为94.6%和67.6%,P=0.003)、校正的TIMI帧数25帧获得率(分别为91.9%和64.9%,P=0.005)、术后90 min心电图ST段回落百分比(sumSTR)(分别为67.6%和27.0%,P=0)、术后1周的射血分数[(56.62±6.897)和(51.59±6.817),P=0.002)]高于对照组,而两组的TIMI 3级血流的获得率以及两组住院期间的主要心血管事件发生率、出血事件发生率差异无显著性(P0.05)。结论在急性心肌梗死患者行急诊PCI治疗中冠脉内注射替罗非班继之静脉维持是安全的,可以提高心肌微血管水平的灌注,从而改善患者的短期临床预后,长期预后情况仍需进一步研究。     

早期使用国产替罗非班对急性ST段抬高心肌梗死患者血管血流及临床预后的影响

目的评价国产血小板糖蛋白IIb/IIIa受体拮抗剂替罗非班对急性ST段抬高心肌梗死(STEMI)患者直接经皮冠状动脉介入治疗(PCI)术前梗死相关血管(IRA)血流和临床预后的影响.方法2005年1月-2006年12月,共42例接受急诊直接PCI治疗的急性心肌梗死患者纳入研究,随机分为替罗非班组(26例)和对照组(16例).比较2组间的基础临床资料、PCI术前造影情况、出血发生率、PCI术后肌钙蛋白I(TNI)峰值以及住院期间主要心血管事件发生率.结果2组基础临床资料和住院期间主要心血管事件发生率均无显著性差异(P＞0.05);替罗非班组PCI术前心肌梗死溶栓研究血流分级(TIMI)优于对照组;尽管替罗非班组的出血发生率稍高于对照组,但无统计学意义(P＞0.05);且替罗非班组术后TNI峰值较对照组低[(18.7±7.5)μg·_L-1vs(23.9±5.9)μg·L-1,P＜0.05)].结论急性STEMI患者选择直接PCI术时尽早使用国产替罗非班是安全的,可以改善PCI术前的IRA的TIMI血流和临床预后.     

替罗非班冠脉内注射对急性心肌梗死患者冠状动脉介入治疗预后的影响

目的观察替罗非班冠脉内注射对ST段抬高性急性心肌梗死(STE-MI)患者急诊冠状动脉介入治疗(PCI)预后的影响。方法将48例STEMI患者随机分为常规治疗组和替罗非班组,每组各24例。2组均给予常规药物治疗和急诊PCI治疗;在此基础上,替罗非班组在PCI时,冠脉内注射替罗非班(10μg.kg-1),术后以负荷量(0.4μg.kg-1.min-1,30 min)、然后维持量(0.1μg.kg-1.min-1)治疗48～72 h;用心肌梗死溶栓试验(TI-MI)和校正的TIMI计帧数(CTFC)测量法,评估PCI术后即刻结果、临床疗效、心肌损伤标志物水平、心血管事件和不良反应。结果 PCI后,TIMI血流3级获得率,替罗非班组高于常规治疗组(P=0.045);替罗非班组的CT-FC值小于常规治疗组(P=0.000)。治疗后3,7 d,血清CK、CK-MB和cT-nI水平,替罗非班组低于常规治疗组(均P<0.05)。结论替罗非班冠脉内注射治疗急性心肌梗死患者安全有效。     

替罗非班联合急诊PCI治疗急性ST段抬高型心肌梗死的获益与风险

目的：讨论替罗非班联合急诊PCI治疗急性ST段抬高型心肌梗死（STEMI）的获益与风险。方法：选取本院门诊发现的110例急性ST段抬高性心肌梗死经冠状动脉造影及接受急诊介入治疗的患者,被随机分为PCI术前使用替罗非班组（A组,55例）,对照组（B组,55例）。从而观察两组患者介入治疗中梗死相关动脉（IRA）的TIMI血流情况、出血发生率。结果：A组与B组心肌梗死溶栓试验分级TIMI和3级血流的比较,患者在术前、术中无明显差异（P〉0.05）,冠状动脉造影复查术后A组较B组患者TIMI血流3级明显增高,同时出血风险率上升,但出血风险率差异无统计学意义（P〉0.05）,两组均无严重出血并发症。结论：早期使用替罗非班对急性ST段抬高型心肌梗死（STEMI）急诊PCI时梗死相关动脉（IRA）的复流获益大于风险,无明显出血并发症。     

替罗非班在急性心肌梗死患者PCI中的应用

目的观察替罗非班冠脉内注射及/或静脉注射对ST段抬高性急性心肌梗死(AMI)患者冠状动脉介入治疗(PCI)预后的影响。方法将113例STEMI患者随机分为常规治疗组(对照组)60例和替罗非班组(治疗组)53例。2组均给予常规药物治疗和PCI治疗;在此基础上替罗非班组在PCI时,冠脉内注射替罗非班10μg/kg,术后以维持量0.1μg·kg-1·min-1由静脉微泵维持泵入24~48 h;用心肌梗死溶栓试验(TIMI)和校正的TIMI计帧数(CTFC)测量法,评估PCI术后即刻结果、临床疗效、心肌损伤标志物水平、心血管事件和不良反应。结果 PCI后,TIMI血流3级获得率,替罗非班组高于常规治疗组(P=0.046)。结论替罗非班冠脉内注射治疗急性心肌梗死患者安全有效。     

Clinical Observation of Tirofiban Treatment on No-Flow Phenomenon in Patients with Acute ST-Elevation Myocardial Infarction during Percutaneous Coronary Intervention

目的:观察冠脉内注射替罗非班对急性ST段抬高型心肌梗死(STEMI)患者急诊经皮冠状动脉介入(PCI)治疗术中无复流的疗效.方法:将82例急性STEMI行急诊PCI术且术中出现无复流现象的患者分为2组,替罗非班组(48例)于冠脉内注入替罗非班10 μg· kg-1,5 min内注射完毕,继以0.15μg· kg-1·min-1静脉维持38 h;对照组(34例)于冠脉内注入维拉帕米200 μg,15 min内注射完毕.观察2组给药后20 min心肌梗死溶栓试验(TIMI)血流分级、TIMI心肌灌注分级(TMPG)和校正的TIMI帧数(CTFC).结果:给药后20 min,替罗非班组TIMI血流和TMPG心肌灌注3级获得率高于对照组,差异有统计学意义.给药前2组CTFC帧数差异无统计学意义,给药后20 min替罗非班组CTFC低于对照组,差异有统计学意义.结论:冠脉内注射替罗非班可以有效地改善STEMI急诊PCI术中无复流的现象.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

2-(Acetoxyphenyl)-(Z)-styryl sulfides as cyclooxygenase inhibitors

2-(Acetoxyphenyl)-(Z)-styryl sulfides are described as selective cyclooxygenase-2 (COX-2) inhibitors, useful for treating inflammation and COX-2-mediated disorders including neoplasia. 2-(Acetoxyphenyl)-(Z)-styryl sulfide is claimed to be the most potent COX inhibitor in the series with a COX-2 selectivity ratio of 33. This compound is also claimed to be superior to celecoxib (Celebrex^®, Pfizer) in inhibiting cell growth of colorectal carcinoma cells. In this evaluation, the COX inhibitory activity of this compound is compared to that previously disclosed for diarylheterocycles and 2-(acetoxyphenyl)alkyl sulfides. The validity of the DLD-1 cell line in the growth inhibition studies is questioned based on recent literature reports indicating the lack of COX-2 expression in this cell line.     

Sleep-disordered breathing with chronic opioid use

Chronic opioid use for pain relief or as substitution therapy for illicit drug abuse is prevalent in our societies. In the US, retail distribution of methadone and oxycodone has increased by 824 and 660%, respectively, between 1997 and 2003. μ-Opioids depress respiration and deaths related to illicit and non illicit chronic opioid use are not uncommon. Since 2001 there has been an emerging literature that suggests that chronic opioid use is related to central sleep apnoea of both periodic and non-periodic breathing types, and occurs in ～ 30% of these subjects. The clinical significance of these sleep-related abnormalities are unknown. This review addresses the present knowledge of control of ventilation mechanisms during wakefulness and sleep, the effects of opioids on ventilatory control mechanisms, the sleep-disordered breathing found with chronic opioid use and a discussion regarding the future research directions in this area.     

Drug targets for cognitive enhancement in neuropsychiatric disorders

The investigation of novel drug targets for treating cognitive impairments associated with neurological and psychiatric disorders remains a primary focus of study in central nervous system (CNS) research. Many promising new therapies are progressing through preclinical and clinical development, and offer the potential of improved treatment options for neurodegenerative diseases such as Alzheimer's disease (AD) as well as other disorders that have not been particularly well treated to date like the cognitive impairments associated with schizophrenia (CIAS). Among targets under investigation, cholinergic receptors have received much attention with several nicotinic agonists (α7 and α4β2) actively in clinical trials for the treatment of AD, CIAS and attention deficit hyperactivity disorder (ADHD). Both glutamatergic and serotonergic (5-HT) agonists and antagonists have profound effects on neurotransmission and improve cognitive function in preclinical experiments with animals; some of these compounds are now in proof-of-concept studies in humans. Several histamine H3 receptor antagonists are in clinical development not only for cognitive enhancement, but also for the treatment of narcolepsy and cognitive deficits due to sleep deprivation because of their expression in brain sleep centers. Compounds that dampen inhibitory tone (e.g., GABA_A α5 inverse agonists) or elevate excitatory tone (e.g., glycine transporter inhibitors) offer novel approaches for treating diseases such as schizophrenia, AD and Down syndrome. In addition to cell surface receptors, intracellular drug targets such as the phosphodiesterases (PDEs) are known to impact signaling pathways that affect long-term memory formation and working memory. Overall, there is a genuine need to treat cognitive deficits associated with many neuropsychiatric conditions as well as an increasingly aging population.