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Outcomes of systemic thrombolysis with reteplase in high-risk acute pulmonary embolism. 雷替普酶全身性溶栓治疗高危急性肺栓塞的疗效。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-04-16 eCollection Date: 2025-03-01 DOI: 10.1515/jbcpp-2024-0188
Leila Bigdelu, Mahla Deldar, Asal Yadollahi, Vafa Baradaran Rahimi

Objectives: High-risk pulmonary embolism (PE) is known as the presence of hemodynamic instability and has a high mortality rate, which necessitates immediate reperfusion treatment. According to current PE treatment guidelines, alteplase is the approved and preferred agent for systemic thrombolysis. Herein, we present the efficacy and safety of systemic thrombolysis with reteplase in patients with high-risk PE.

Methods: The present retrospective observational study includes 30 patients with high-risk acute PE undergoing systemic thrombolysis with reteplase. All patients were in obstructive shock. The thrombolytic regimen consisted of two bolus doses of 10 U reteplase, given 30 min apart, followed by intravenous heparin.

Results: All patients had elevated cardiac troponin levels. D-dimer levels were elevated in 28 (93.3 %) patients. Systolic blood pressure increased after thrombolysis with reteplase, and the dyspnea, tachypnea, and coughing improved in all patients. Mean SPO2 was 83.6 ± 6.96 % before treatment, which had risen to 95.7 ± 1.29 % after thrombolysis (p=0.059). Right ventricular dilatation was seen in all patients at presentation, which improved by 96.6 % after treatment and systolic pulmonary artery pressure decreased significantly in all patients at discharge. None of the patients needed to repeat thrombolytic therapy. There were no major hemorrhagic complications or death after thrombolysis, while 5 (16.7 %) patients experienced minor self-limiting bleeding.

Conclusions: Reteplase, as two bolus injections of 10 U given 30 min apart, is an effective thrombolytic regimen in treating acute high-risk PE with a low risk of major hemorrhagic complications.

目的:高危肺栓塞(PE)以血流动力学不稳定著称,死亡率高,需要立即进行再灌注治疗。根据目前的PE治疗指南,阿替普酶是被批准的首选全身溶栓药物。在此,我们展示了瑞替普酶全身性溶栓治疗高危PE患者的有效性和安全性。方法:本回顾性观察研究包括30例接受瑞替普酶全身溶栓治疗的高危急性PE患者。所有患者均为梗阻性休克。溶栓方案包括两次大剂量10 U reteplase,间隔30 分钟,然后静脉注射肝素。结果:所有患者心肌肌钙蛋白水平均升高。28例(93.3 %)患者d -二聚体水平升高。reteplase溶栓后收缩压升高,呼吸困难、呼吸急促、咳嗽改善。治疗前平均SPO2为83.6±6.96 %,溶栓后平均SPO2为95.7±1.29 % (p=0.059)。所有患者在就诊时均出现右心室扩张,治疗后改善96.6% %,出院时肺动脉收缩压明显下降。所有患者均无需重复溶栓治疗。溶栓后无重大出血并发症或死亡,有5例(16.7 %)出现轻度自限性出血。结论:瑞替普酶(Reteplase)是治疗急性高危PE的有效溶栓方案,每次10 U,每次30 min。
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引用次数: 0
Oxygen Toxicity as a Function of Time and Po2. 氧毒性与时间和Po2的关系。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-04-10 Print Date: 1994-01-01 DOI: 10.1515/jbcpp-1994-050106
Ran Arieli

The quantification of 0 2 toxicity as a function of exposure time (t) and Po2 has been based mainly on the empirical rectangular hyperbola. The non-linear response of the 02-damaged physiological variable (DMG) as a function of time at constant Po2 can be related to the dependence of dDMG/dt on the DMG. The kinetics of the 02 - derived chemical species suggests a power relationship between the DMG and Po2 rather than a linear relationship. The combination of time and Po2 considerations suggests two models: 1) DMG = a(ebt - l)Po2 c and 2) DMG = a-tbPo2 c, where a, b and c are constant. Non-linear regression of the different parameters of 0 2 toxicity showed a preference for model 2, with b=2. Possible mechanisms underlying the kinetics of 0 2 toxicity and the use of the equation for its prediction are discussed.

0 2毒性作为暴露时间(t)和Po2的函数的量化主要基于经验矩形双曲线。恒定Po2条件下02-损伤生理变量(DMG)随时间的非线性响应可能与dDMG/dt对DMG的依赖性有关。02衍生化学物质的动力学表明DMG和Po2之间存在幂函数关系,而不是线性关系。结合时间和Po2的考虑,可以得到两个模型:1)DMG = a(ebt - l) po2c和2)DMG = a- tbpo2c,其中a、b和c为常数。对0 2毒性各参数进行非线性回归,结果表明模型2更优,b=2。讨论了0 - 2毒性动力学的可能机制以及该方程用于其预测的应用。
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引用次数: 0
CONTENTS. 内容。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-04-10 Print Date: 1994-01-01 DOI: 10.1515/jbcpp-1994-toc0501
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引用次数: 0
Magnesium Protects Against Anaphylactic Shock and Cardiac Myolysis in Guinea-Pigs. 镁对豚鼠过敏性休克和心肌溶解的保护作用。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-04-10 Print Date: 1994-01-01 DOI: 10.1515/jbcpp-1994-050104
Fabio Kusniec, Gabriella Fischer, Ben-Ami Sela, Yaakov Ashkenazy, Dan Fiegel, Sandra Moshonov, Uriel Zor

The pathophysiological responses to immune stress (IS) include activation of several processes which are dependent on cytosolic Ca2+ elevation. Magnesium frequently acts as a natural Ca2+ antagonist. In this study we have observed that Mg2 + can protect guinea-pigs against IS. Antigen-sensitized guinea-pigs, which had been fed a magnesiumdeficient diet, were given a single dose (15 mg) of MgCl2 intraperitoneally 1 h before antigen challenge. The development of anaphylactic shock (AS) was observed during the next 2 h, and the hearts were subsequently examined histologically for signs of cardiac myolysis (CM). Magnesium (i) reduced the incidence of CM from 40% to 10% (p<0.05); (ii) reduced the incidence of AS from 61% to 35% (p<0.05); (iii) attenuated the severity of the AS; and (iv) lowered mortality from 39% in the control to 19% in the Mg2+-treated group (p=0.1). Serum and tissue total [Mg2+] were not affected by the administration of MgCl2. Also, the serum and heart Mg2+ levels were the same whether or not the guinea-pigs developed AS or CM. In cell culture we demonstrated that by elevating the [Mg2+] in the medium bathing sensitized rat basophilic leukemia (RBL) cells, the increase in cytosolic [Ca2+] subsequent to antigen challenge was reduced from 174 ± 23.28% (1 mM) to 82.74 ± 13.22 % (3 mM). We conclude that a single treatment with Mg2+ can considerably diminish damage induced by immune stress, probably by its altering the Ca2+: Mg2+ratio. Since the physiological reaction to different types of stress is similar, Mg2 + could prove beneficial in preventing stress-induced shock in general. Studies examining the mechanisms by which Mg2 + exerts its effects thus provide a scientific basis for the current clinical use of Mg2 + in acute myocardial infarction (AMI) and asthma.

对免疫应激(IS)的病理生理反应包括依赖于细胞质Ca2+升高的几个过程的激活。镁经常作为一种天然的Ca2+拮抗剂。在这项研究中,我们观察到Mg2 +可以保护豚鼠对抗IS。饲喂缺镁饲料的抗原致敏豚鼠,在抗原激发前1小时腹腔注射单剂量(15 mg) MgCl2。在接下来的2小时内观察过敏性休克(AS)的发展,随后对心脏进行组织学检查,以寻找心肌溶解(CM)的迹象。镁(i)将CM的发生率从40%降低到10% (p
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引用次数: 0
A New Class of Antiarrhythmic-Defibrillatory Compounds. 一类新的抗心律失常除颤剂化合物。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-04-10 Print Date: 1994-01-01 DOI: 10.1515/jbcpp-1994-050105
M Erez, D Varon

Ventricular fibrillation (VF) is a major cause of sudden cardiac death in humans. Currently used antiarrhythmic drugs are aimed at preventing initiation of VF by decreasing the incidence of arrhythmias which can lead to VF. This approach today seems to be insufficient. On the basis of reports that VF can terminate spontaneously in various mammals, and even in humans, we propose pharmaceutical enhancement of self-ventricular defibrillation as a new therapeutical approach. Data obtained over the last decade indicate that a high cardiac extraneuronal norepinephrine level during VF facilitates selfdefibrillation. Dibenzazepines (tricyclic antidepressants) and phenothiazines elevate norepinephrine level by inhibiting norepinephrine reuptake and were found to exhibit defibrillatory activity. The relationship of chemical structure to defibrillatory activity was studied in a group of dibenzazepine and phenothiazine compounds.

心室颤动(VF)是人类心源性猝死的主要原因。目前使用的抗心律失常药物旨在通过减少可导致室性心律失常的发生率来预防室性心律失常的发生。这种方法在今天看来是不够的。基于各种哺乳动物甚至人类的心室纤颤可以自发终止的报道,我们建议药物增强自我心室除颤作为一种新的治疗方法。过去十年获得的数据表明,在心室颤动期间,高的心神经外去甲肾上腺素水平有助于自我除颤。二苯氮卓类药物(三环抗抑郁药)和吩噻嗪类药物通过抑制去甲肾上腺素再摄取来提高去甲肾上腺素水平,并被发现具有除颤活性。研究了一组二氮卓类和吩噻嗪类化合物的化学结构与除颤剂活性的关系。
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引用次数: 0
Ion-Selective Channels in K562 Cells: A Patch-Clamp Analysis. K562细胞中的离子选择通道:一个膜片钳分析。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-04-10 Print Date: 1994-01-01 DOI: 10.1515/jbcpp-1994-050103
Jürgen Rettinger, Wolfgang Schwarz

Four types of ion-selective channels were found by the patch-clamp technique in the human erythroleucemia K562 cells. I)In cell-attached configuration at potentials less negative than -40 mV an 8 pS channel was detected. The potential dependence of channel activity suggests that this is the TTX-sensitive Na+ channel. II)A cation-selective channel was observed with equal permeability for Na+ and K+ and a potential-independent single-channel conductance of 19 pS. The channel is activated by intracellular Ca2+ and inhibited by TEA. ΙΠ)A predominantly anion-selective channel was identified with the selectivity sequence N03" >J" > G" = Br » S04 2·. The single-channel conductance shows outward rectification, and is in symmetrical NaCl solution 19 pS at -60 mV and 54 pS at +50 mV. The open- and closedtime distributions suggest one open and at least four closed states. At submicromolar concentrations, the open state is blocked by H2DIDS leading to channel flicker between open and blocked channel; higher concentrations (apparent Kj=6.8 μΜ) lead to a longer-lasting blocked state. Both components of inhibition are reversible. IV)In addition, an 8 pS, Na+- and K+- selective channel could be induced by application of palytoxin. For channel activity, the presence of extracellular Na+ is essential. It is assumed that the Na+, K+-pump molecule is involved in the channel formation. Similarly, it is discussed whether the anionselective channel represents a pore conformation of an electrically silent anion exchanger.

利用膜片钳技术在人红细胞K562细胞中发现了四种类型的离子选择通道。I)在电位小于负-40 mV的细胞连接配置下,检测到8ps通道。通道活性的潜在依赖性表明这是ttx敏感的Na+通道。II)观察到一个阳离子选择性通道,对Na+和K+具有相同的通透性,并且具有不依赖电位的19 pS的单通道电导。该通道被细胞内Ca2+激活,并被TEA抑制。ΙΠ)通过选择性序列N03" >J" > G" = Br»S04 2·确定了一个阴离子选择性通道。单通道电导表现为向外整流,在对称NaCl溶液中-60 mV时为19 pS, +50 mV时为54 pS。开放和封闭时间分布表明有一个开放状态和至少四个封闭状态。在亚微摩尔浓度下,打开状态被H2DIDS阻断,导致通道在打开和阻塞通道之间闪烁;较高的浓度(表观Kj=6.8 μΜ)导致更持久的阻滞状态。抑制的两个组成部分都是可逆的。IV)此外,应用孢毒素可诱导8 pS, Na+-和K+-选择性通道。对于通道活性,细胞外Na+的存在是必不可少的。假设Na+, K+泵浦分子参与了通道的形成。同样,讨论了阴离子选择通道是否代表电沉默阴离子交换器的孔构象。
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引用次数: 0
Dehydration and Rehydration in Donkeys: The Role of the Hind Gut as a Water Reservoir. 驴的脱水和补液:后肠作为贮水器的作用。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-04-10 Print Date: 1994-01-01 DOI: 10.1515/jbcpp-1994-050107
H Kasirer-Izraely, I Choshniak, A Shkolnik

Body fluid distribution was measured in three donkeys, fully hydrated, following dehydration and after being rapidly rehydrated. In twenty other donkeys that were slaughtered to supply food for predators iri a safari zoo, the water content in the different compartments of the gastrointestinal tract (GIT) was assessed. Prior to being slaughtered, four of the animals were fully hydrated, four dehydrated and 12 dehydrated, rehydrated and then slaughtered and examined, four at 1, four at 3 and four at 5 hours following drinking. When the body mass of dehydrated donkeys dropped to 75.4± 2.4% of their initial value, total body water of the animals (HTO space), extracellular volume (SCN space) and plasma volume (EB space) were reduced to 76.6 ± 5.3%, 80.9 ± 10.6% and 73.2 ± 8.3% of their initial values, respectively. The amount of water retained in the GIT of the fully hydrated donkeys amounted to 15.9 ± 3.4 1, 19% of total body water. In the dehydrated donkeys it was only 7.4± 1.3 1. The calculated total intracellular volume in the dehydrated donkeys was only 14% lower than in the fully hydrated animals. When drinking was allowed, dehydrated donkeys consumed 17.6 ± 2.4 1 of water. The increase in the water content in the gut of newly rehydrated donkeys matched this volume, 80% of which was retained in the hind gut. During the five hours after drinking, only slow and moderate changes in the volume of the hind gut were recorded. Changes in plasma volume were also suppressed. It is suggested that the hind gut of the donkey, similar to the rumen of goats and sheep, plays a role as a water reservoir that helps maintain the osmotic stability of the body.

测量了3头完全水合、脱水和快速水合后的驴的体液分布。在另外20头被屠宰的驴中,为野生动物园的捕食者提供食物,评估了胃肠道不同隔室(GIT)的含水量。屠宰前,4只动物完全补水,4只脱水,12只脱水,再补水后屠宰并检查,4只在饮水后1小时,4只在3小时,4只在5小时。当脱水驴体质量降至初始值的75.4±2.4%时,动物总含水量(HTO空间)、细胞外体积(SCN空间)和血浆体积(EB空间)分别降至初始值的76.6±5.3%、80.9±10.6%和73.2±8.3%。全水合驴胃中保留的水分占全身水分的15.9±3.4,占全身水分的19%。而脱水后的驴仅为7.4±1.3。脱水驴的计算总细胞内体积仅比完全水合驴低14%。在允许饮水时,脱水驴的饮水量为17.6±2.4。新水合后的驴子肠道含水量的增加与此量相匹配,其中80%保留在后肠。在饮酒后的5小时内,只记录了后肠体积的缓慢和中度变化。血浆容量的变化也被抑制。这表明,驴的后肠,类似于山羊和绵羊的瘤胃,起着蓄水池的作用,帮助维持身体的渗透稳定性。
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引用次数: 0
Anions, Membrane Resistance and Ventricular Fibrillation. 阴离子、膜阻力与心室颤动。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-04-10 Print Date: 1994-01-01 DOI: 10.1515/jbcpp-1994-050102
Michael J Curtis, Paul D Ridley

Clinical success in prevention of sudden cardiac death has been poor. New approaches to prevention of ventricular fibrillation (VF), one of the main causes of sudden cardiac death, are clearly needed. In the present article we have reviewed some of our own data which support the notion that VF may be prevented by manipulation of chloride homeostasis /1,2/. Our studies have revealed a novel approach to VF suppression via alteration of sarcolemmal membrane resistance.

预防心源性猝死的临床成功率一直很低。心室颤动(VF)是心源性猝死的主要原因之一,显然需要新的预防方法。在本文中,我们回顾了一些我们自己的数据,这些数据支持通过控制氯化物稳态来预防VF的观点。我们的研究揭示了一种通过改变肌上皮膜抗性来抑制VF的新方法。
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引用次数: 0
Chemical Defibrillation in Acute Myocardial Ischaemia: a Hypothesis. 急性心肌缺血的化学除颤:一个假说。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-04-10 Print Date: 1994-01-01 DOI: 10.1515/jbcpp-1994-050101
Michael J Curtis
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引用次数: 0
Point-of-care testing: revolutionizing clinical biochemistry using decentralized diagnostics. 即时检测:使用分散式诊断革新临床生物化学。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-04-04 eCollection Date: 2025-03-01 DOI: 10.1515/jbcpp-2025-0029
Simran Shaikh, Sanjyoti A Panchbudhe, Rajni R Shivkar, Arnab Banerjee, Paulami Deshmukh, Charushila Y Kadam

Point-of-care testing (POCT) refers to decentralized testing done using complex but compact, portable devices that can be done near the site at the patient's bedside. These enable quick diagnosis and timely intervention because turnaround time (TAT) decreases with these devices. They can also be operated by non-medical personnel and patients with minimum expertise as these devices are easy to handle and interpret. This increases patient awareness regarding their diseases and benefits doctors in giving more patient-centered care. POCT devices require minimum setup and can be utilized even in remote places. The present review focuses on POCT devices employed specifically in clinical biochemistry, e.g., glucose, HbA1c, cardiac biomarkers, fertility tests, hematological analysis, electrolytes, enzymes, urine dipstick tests, etc. This introductory review delves into comprehending the fundamentals of POCT technologies, their guidelines, applications, advantages, and disadvantages. It covers a broad overview of the tests done and the samples required to process these tests. It also compares the pros and cons of POCT devices over centralized laboratory testing. The review also aims to emphasize the relevance of its use in today's era, current trends regarding POCT in urban and rural setups, challenges faced in the field during its implementation, and the potential areas of improvement in the future. However, it is advisable to seek references for more detailed and critical information regarding all the specific topics given in this review article.

护理点检测(POCT)是指使用复杂但紧凑的便携式设备进行的分散检测,这些设备可以在患者床边附近进行。由于这些设备减少了周转时间(TAT),因此可以快速诊断和及时干预。它们也可以由非医务人员和具有最少专业知识的患者操作,因为这些设备易于操作和解释。这提高了患者对自己疾病的认识,有利于医生提供更多以患者为中心的护理。POCT设备需要最少的设置,甚至可以在偏远的地方使用。本文综述了POCT设备在临床生物化学中的应用,如葡萄糖、糖化血红蛋白、心脏生物标志物、生育试验、血液学分析、电解质、酶、尿试纸试验等。这篇介绍性的综述深入了解POCT技术的基本原理、它们的指导方针、应用、优点和缺点。它涵盖了所完成的测试和处理这些测试所需的样本的广泛概述。它还比较了POCT设备与集中实验室测试的优缺点。该审查还旨在强调其在当今时代使用的相关性,目前在城市和农村设置中关于POCT的趋势,实施过程中现场面临的挑战以及未来可能改进的领域。然而,对于这篇综述文章中给出的所有特定主题,建议寻求更详细和关键的信息。
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引用次数: 0
期刊
Journal of Basic and Clinical Physiology and Pharmacology
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