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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
Approaching a phenomenal contradiction in acid-base physiology. 接近酸碱生理学中一个显著的矛盾。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-03-31 eCollection Date: 2025-03-01 DOI: 10.1515/jbcpp-2025-0016
Stelios Kokkoris, Kyriakos Trigkidis, Dimitrios-Dorotheos Papadakis, Dimitrios Kostarakis, Nikolaos Gialelis, Ioannis Vasileiadis

Objectives: The study focuses exclusively on the results of an arterial blood gas report, which reveal a phenomenal contradiction if one follows the physiological and physicochemical approaches as well as the standard base excess determination to interpret an acid-base disturbance. The aim of this article is not to fully describe a clinical case and make a differential diagnosis but to analyze the blood gas report data in detail and present the conclusions that result from the application of the different approaches that exist for the interpretation of acid-base disorders.

Methods: The results of an arterial blood gas report of a patient with severe lactic acidosis were cross-examined using the standard base excess method and the physiologic and physiochemical approaches. The causes of the contradiction are discussed with a commentary on the underlying pathophysiology.

Results: The study revealed the presence of a normal anion gap (even after correction for albumin levels), a slightly increased strong ion gap and a moderately decreased standard base excess in a patient with severe lactic acidosis.

Conclusions: This real-life case provides an opportunity to give a brief overview of the current methods for investigating acid-base disturbances in a practical way, emphasizing both the common background and the conceptual differences and similarities.

目的:本研究仅关注动脉血气报告的结果,如果遵循生理和物理化学方法以及标准碱过量测定来解释酸碱失调,则会发现一个惊人的矛盾。本文的目的不是完全描述一个临床病例并做出鉴别诊断,而是详细分析血气报告数据,并提出应用不同方法解释酸碱失调所得到的结论。方法:对1例重度乳酸酸中毒患者的动脉血气报告结果,采用标准碱过量法和生理、理化方法进行交叉检验。讨论了矛盾的原因,并对潜在的病理生理学进行了评论。结果:该研究显示,在严重乳酸酸中毒患者中存在正常的阴离子间隙(即使在白蛋白水平校正后),强离子间隙略有增加,标准碱过量适度减少。结论:这个现实生活中的案例提供了一个机会,简要概述了当前以实际方式研究酸碱干扰的方法,强调了共同的背景和概念上的差异和相似性。
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引用次数: 0
Incretin-based therapies: advancements, challenges, and future directions in type 2 diabetes management. 基于肠促胰岛素的治疗:2型糖尿病治疗的进展、挑战和未来方向。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-03-31 eCollection Date: 2025-03-01 DOI: 10.1515/jbcpp-2025-0031
Amruth A Alluri, Yashaswi Guntupalli, Shruti Suresh Suvarna, Yuliya Prystupa, Shrishti Prakash Khetan, Bharath Vejandla, Naraginti Lenin Babu Swathi

Incretin-based medicines have considerably impacted the treatment of type 2 diabetes mellitus (T2DM), providing considerable advantages in glycemic regulation, weight control, and cardiovascular results. This narrative review examines progress in incretin medicines, encompassing glucagon-like peptide-1 (GLP-1) receptor agonists, dual-receptor, and triple-receptor agonists, while emphasizing their therapeutic advantages, obstacles, and prospective developments. The examined articles were sourced from databases including PubMed and Google Scholar, concentrating on publications predominantly from 2010 to 2024. Selective foundational papers released before this timeline were incorporated to furnish critical historical context about incretin processes and their discovery. Incretin-based medicines, despite their therapeutic efficacy, encounter hurdles including elevated treatment costs, patient compliance difficulties, and variability in response attributable to genetic and physiological variables. Moreover, there are still deficiencies in comprehending the long-term cardiovascular safety and cancer risks linked to these medicines. Emerging dual- and triple-receptor agonists demonstrate potential in overcoming the shortcomings of conventional GLP-1 receptor agonists, providing enhanced metabolic results and broader uses in intricate disease profiles. Future research must concentrate on economic obstacles, streamlined regimens, customized medicine, the integration of artificial intelligence, patient stratification, as well as the safety and efficacy of incretin-based medicines for holistic management of T2DM.

以肠促胰岛素为基础的药物对2型糖尿病(T2DM)的治疗有很大的影响,在血糖调节、体重控制和心血管结果方面提供了相当大的优势。本文回顾了肠促胰岛素药物的进展,包括胰高血糖素样肽-1 (GLP-1)受体激动剂、双受体激动剂和三受体激动剂,同时强调了它们的治疗优势、障碍和前景发展。被检查的文章来自PubMed和b谷歌Scholar等数据库,主要集中于2010年至2024年的出版物。选择性的基础论文发布之前,这个时间表被纳入提供关键的历史背景肠促胰岛素过程和他们的发现。以肠促胰岛素为基础的药物,尽管具有治疗效果,但遇到了一些障碍,包括治疗费用增加,患者依从性困难,以及可归因于遗传和生理变量的反应可变性。此外,在理解与这些药物相关的长期心血管安全性和癌症风险方面仍然存在不足。新兴的双受体和三受体激动剂显示出克服传统GLP-1受体激动剂缺点的潜力,提供增强的代谢结果和更广泛的应用于复杂的疾病特征。未来的研究必须集中在经济障碍、简化方案、定制药物、人工智能的整合、患者分层以及基于肠促胰岛素的药物对T2DM整体管理的安全性和有效性上。
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引用次数: 0
Elevated seminal plasma leptin may correlate with varicocele presence and BMI. 精浆瘦素升高可能与精索静脉曲张存在和BMI相关。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-03-28 eCollection Date: 2025-03-01 DOI: 10.1515/jbcpp-2025-0010
Humam D Mohammed, Rana R Al-Saadi, Estabraq A R Al-Wasiti

Objectives: Male infertility affects 20-30 % of infertile couples worldwide, and varicocele being a common cause. The relationship between leptin, a hormone involved in energy homeostasis and reproduction, and male fertility parameters remains incompletely understood, particularly in the context of varicocele and obesity. Thus, the current study sought to assess the associations between seminal plasma leptin and other clinical and demographic data of infertile patients.

Methods: In this cross-sectional study, 90 men (29 with varicocele, 61 without) were evaluated from November 2023 to March 2024. Seminal plasma leptin levels were measured using ELISA. Study subjects were classified into three weight classifications using body mass index (BMI) measurements: normal weight, overweight, and obese. Semen analysis, reproductive hormones assessment, and correlation analyses were performed to examine relationships between leptin levels and various clinical parameters.

Results: Patients with varicocele demonstrated significantly higher seminal plasma leptin levels compared to those without (9.27 vs. 7.65 ng/mL, p<0.05), this association persisted following statistical adjustment for demographic and clinical variables. In addition, BMI was the strongest independent predictor of seminal plasma leptin levels (β=0.26, p<0.01). Interestingly, overweight individuals showed higher leptin levels than both normal weight and obese participants. A significant inverse relationship found between leptin concentrations and luteinizing hormone levels (ρ=-0.375, p<0.05), while a positive association was found with progressive motility of sperm (ρ=0.225, p<0.05).

Conclusions: Higher levels of leptin were found in seminal specimens of varicocele-diagnosed subjects and strongly correlate with BMI in this Middle Eastern population. These results together propose that leptin's level in semen could be useful as a biological indicator for varicocele-associated male fertility issues.

目的:男性不育影响20-30 %的不育夫妇,精索静脉曲张是一个常见的原因。瘦素(一种参与能量平衡和生殖的激素)与男性生育参数之间的关系仍不完全清楚,特别是在精索静脉曲张和肥胖的背景下。因此,本研究旨在评估精血浆瘦素与不育患者的其他临床和人口统计学数据之间的关系。方法:在这项横断面研究中,从2023年11月到2024年3月,对90名男性(29名患有精索静脉曲张,61名没有)进行了评估。采用ELISA法测定精血瘦素水平。研究对象根据身体质量指数(BMI)被分为三种体重类别:正常体重、超重和肥胖。通过精液分析、生殖激素评估和相关分析来检验瘦素水平与各种临床参数之间的关系。结果:精索静脉曲张患者的精血瘦素水平明显高于无精索静脉曲张患者(9.27 vs. 7.65 ng/mL)。结论:精索静脉曲张患者的精血瘦素水平较高,且与中东人群的BMI密切相关。这些结果共同表明,精液中的瘦素水平可以作为精索静脉曲张相关男性生育问题的生物学指标。
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引用次数: 0
The need for quality certification for urological apps. 泌尿科应用需要质量认证。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2025-03-25 eCollection Date: 2025-03-01 DOI: 10.1515/jbcpp-2025-0032
Guglielmo Mantica, Francesco Chierigo
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引用次数: 0
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Journal of Basic and Clinical Physiology and Pharmacology
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