MINECRAFT Study: MINEralcorticoid Receptor Antagonism With CanRenone As eFfective Treatment in Moderate to Severe ARDS in COVID-19, a Phase 2 Clinical Trial.

The main aim of the study is to estimate the potential efficacy of i.v. canrenone as add-on therapy on maximal medical treatment versus maximal medical treatment alone in treating moderate-to-severe ARDS due to SARS-CoV-2.

开始日期2022-09-01

申办/合作机构

Fondazione IRCCS Ca' Granda

[+2]

NCT04714710 / Active, not recruiting临床2期IIT

Evaluation of the Hemodynamic Stability of Potassium Canrenoate in Brain-dead Organ Donors: Randomized Controlled Clinical Trial

Given the current organ shortage, improving the quality/efficacy of harvested grafts from expanded criteria donors is essential to substantially increase the number of potential donors. Preclinical studies have shown that blocking the vascular mineralocorticoid receptor (MR) mitigates ischemia-reperfusion injury (I/R) and prevents renal dysfunction following acute kidney injury. Potassium canrenoate is an intravenous MR antagonist. Blocking the MR upstream from aortic cross clamping is likely the most effective strategy to limit I/R injury.
Yet, brain-dead donors are prone to severe hemodynamic instability and polyuria. Consequently, this study seeks to assess the hemodynamic tolerance of the use of potassium canrenoate in this context, as a first step to a large-scale clinical trial testing the impact of this therapeutic intervention on the survival of kidney grafts.

开始日期2021-08-26

申办/合作机构

Centre Hospitalier Regional de Nancy

NCT04912011 / Unknown status临床4期IIT

The Use of a Mineralocorticoid Receptor Antagonist (Spironolactone) in the Treatment of Pulmonary Fibrosis Associated With SARS-CoV-2 Infection

In December 2019 SARS-CoV-2 virus appeared in the world, mainly appearing as an acute infection of the lower respiratory tract. In March 2020, the World Health Organization (WHO) announced a pandemic in relation to the disease caused by the SARS-CoV-2 virus, known as COronaVIrus Disease 2019 (COVID-19). Since then, the efforts of scientists from around the world have focused on finding the right treatment and vaccine for the new disease. COVID-19 has spread rapidly in a few months, affecting patients in all ages. The disease has a varied course, patients can be 80% asymptomatic, but many develop respiratory failure, complicated by sepsis and ultimately death. One of the possible complications associated with COVID-19 lung involvement is pulmonary fibrosis, leading to chronic breathing difficulties and prolonged disability. No specific mechanisms leading to this phenomenon have been identified in COVID-19, but some information is derived from previous studies on the SARS and MERS epidemic. There have been several reports that the use of spironolactone may be important in preventing pulmonary fibrosis.
The aim of the study is to evaluate the effectiveness of intravenous form of mineralocorticoid receptor antagonist canrenoate potassium (an aldosterone antagonist of the spirolactone group) in the treatment of COVID-19-associated pulmonary fibrosis based on the mechanisms of the immune response.

开始日期2021-01-01

申办/合作机构

Pomorski Uniwersytet Medyczny W Szczecinie

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100 项与坎利酸钾相关的转化医学

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100 项与坎利酸钾相关的专利（医药）

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349

项与坎利酸钾相关的文献（医药）

2024-09-01·Physiological Reports

Role of L‐type Ca²⁺‐channels in the vasorelaxing response to finerenone in arteries of human visceral adipose tissue

Article

作者: De Stefano, Alessandro ; Schinzari, Francesca ; Tesauro, Manfredi ; Cardillo, Carmine ; Mettimano, Marco ; Sica, Giuseppe

AbstractInadequate blood supply to the expanding adipose tissue (AT) is involved in the unhealthy AT remodeling and cardiometabolic consequences of obesity. Because of the pathophysiological role of upregulated mineralocorticoid receptor (MR) signaling in the complications of obesity, this study tested the vasoactive properties of finerenone, a nonsteroidal MR antagonist, in arteries of human AT. Arteries isolated from the visceral AT of obese subjects were studied in a wire myograph. Finerenone resulted in a concentration‐dependent relaxation of arteries precontracted with either the thromboxane‐A2 analog U46619, ET‐1, or high‐K+ solution; the steroidal MR antagonist potassium canrenoate, by contrast, did not relax arteries contracted with either U46619 or high‐K+ solution. Finerenone‐induced relaxation after precontraction with U46619 was greater in the arteries of obese versus nonobese subjects. Mechanistically, the vasorelaxing response to finerenone was not influenced by preincubation with the nitric oxide synthase inhibitor L‐NAME or by endothelium removal. Interestingly, finerenone, like the dihydropyridine Ca2+‐channel blocker nifedipine, relaxed arteries contracted with the L‐type Ca2+‐channel agonist Bay K8644. In conclusion, finerenone relaxes arteries of human visceral AT, likely through antagonism of L‐type Ca2+ channels. This finding identifies a novel mechanism by which finerenone may improve AT perfusion, hence protecting against the cardiometabolic complications of obesity.

2024-08-01·Reproductive Sciences

Establishing and Validating an Innovative Focal Adhesion-Linked Gene Signature for Enhanced Prognostic Assessment in Endometrial Cancer

Article

作者: He, Leilei ; Zhang, Yueming ; Ma, Yuhui ; Yan, Cuiyin ; Cheng, Jing ; Shen, Li ; Singla, Rajeev K

Studies have highlighted the significant role of focal adhesion signaling in cancer. Nevertheless, its specific involvement in the pathogenesis of endometrial cancer and its clinical significance remains uncertain. We analyzed TCGA-UCEC and GSE119041 datasets with corresponding clinical data to investigate focal adhesion-related gene expression and their clinical significance. A signature, "FA-riskScore," was developed using LASSO regression in the TCGA cohort and validated in the GSE dataset. The FA-riskScore was compared with four existing models in terms of their prediction performance. We employed univariate and multivariate Cox regression analyses towards FA-riskScore to assess its independent prognostic value. A prognostic evaluation nomogram based on our model and clinical indexes was established subsequently. Biological and immune differences between high- and low-risk groups were explored through functional enrichment, PPI network analysis, mutation mining, TME evaluation, and single-cell analysis. Sensitivity tests on commonly targeted drugs were performed on both groups, and Connectivity MAP identified potentially effective molecules for high-risk patients. qRT-PCR validated the expressions of FA-riskScore genes. FA-riskScore, based on FN1, RELN, PARVG, and PTEN, indicated a poorer prognosis for high-risk patients. Compared with published models, FA-riskScore achieved better and more stable performance. High-risk groups exhibited a more challenging TME and suppressive immune status. qRT-PCR showed differential expression in FN1, RELN, and PTEN. Connectivity MAP analysis suggested that BU-239, potassium-canrenoate, and tubocurarine are effective for high-risk patients. This study introduces a novel prognostic model for endometrial cancer and offers insights into focal adhesion's role in cancer pathogenesis.

2024-01-01·European Journal of Internal Medicine

Renin‐angiotensin-aldosterone system inhibitors and mortality risk in elderly patients with atrial fibrillation. Insights from the nationwide START registry

Article

作者: Pastori, Daniele ; Antonucci, Emilia ; Poli, Daniela ; Palareti, Gualtiero ; Menichelli, Danilo ; Pignatelli, Pasquale

BACKGROUNDArterial hypertension is the most common cardiovascular comorbidity in atrial fibrillation (AF). Few studies investigated management strategies of hypertension in AF.MATERIALS AND METHODSWe included 5769 AF patients on oral anticoagulants from the nationwide ongoing Italian START registry. We investigated the prescription of antihypertensive drugs and mortality risk. Subgroup analyses according to sex and major cardiovascular comorbidities were performed.RESULTSMean age was 80.8 years, 46.1% were women; 80.3% of patients were hypertensive. Furosemide (30.1%) was the most frequent diuretic followed by hydrochlorothiazide (15.4%) and potassium canrenoate (7.9%). 61.1% received β-blockers: 34.2% bisoprolol, 6.2% atenolol. Additionally, 36.9% were on angiotensin converting enzyme inhibitors (ACE-I): ramipril (20.9%), enalapril (5.3%) and perindopril (2.8%); 31.7% were on angiotensin receptors blockers (ARBs): valsartan (7.6%) and irbesartan (6.4%). Amlodipine and lercanidipine were prescribed in 14.0% and 2.3%, respectively. ACE-I (p < 0.001), α-blockers (p = 0.020) and Dihydropyridines calcium channel blockers (p = 0.004) were more common in men, while ARBs (p = 0.008), thiazide diuretics (p < 0.001) and β-blockers (p < 0.001) in women. During 22.61 ± 17.1 months, 512 patients died. Multivariable Cox regression analysis showed that ACE-I (Hazard ratio [HR] 0.758, 95% Confidence Interval [95%CI] 0.612-0.940, p = 0.012) and ARBs (HR 0.623, 95%CI 0.487-0.796, p < 0.001) inversely associated with mortality. ACE-I/ARBs inversely associated with mortality in both sexes and in patients with diabetes. This associastion was evident for ACE-I in patients with previous cardiovascular disease, and for ARBs in HF.CONCLUSIONA lower mortality risk was found in AF patients on ACE-I/ARBs. Different prescription patterns of antihypertensive drugs between men and women do exist.

项与坎利酸钾相关的新闻（医药）

2022-08-25

·生物谷

英国药理学: 局部应用盐皮质激素受体拮抗剂与创面愈合

皮肤动态平衡使皮肤为机体维持一种保护性屏障。由于皮肤是一个界面组织，持续的伤口愈合有助于保持皮肤的动态平衡。皮肤的伤口愈合是一种复杂的现象，由炎症、增殖和生物重塑过程之间的复杂相互作用所协调。皮肤动态平衡使皮肤为机体维持一种保护性屏障。由于皮肤是一个界面组织，持续的伤口愈合有助于保持皮肤的动态平衡。皮肤的伤口愈合是一种复杂的现象，由炎症、增殖和生物重塑过程之间的复杂相互作用所协调。在炎症阶段，巨噬细胞在产生细胞因子、趋化因子、生长和血管生成因子以及刺激细胞增殖和合成组织再生所需物质的代谢物方面发挥核心作用。重要的是，巨噬细胞根据愈合过程的不同阶段表达不同的表型和活动。促炎巨噬细胞在早期阶段被招募到创面区域。图片来源: https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.15932 近日，来自索邦大学的研究者们在Br J Pharmacol杂志上发表了题为Myeloid mineralocorticoid receptor regulates dermal angiogenesis and inflammation in glucocorticoid-induced impaired wound healing的文章，该研究证实了局部MR拮抗可促进巨噬细胞向抗炎表型的转变，从而改善持久的炎症反应，并诱导血管生成，以加速因糖皮质激素治疗而延迟的伤口愈合。伤口愈合延迟是局部皮质激素引起的盐皮质激素受体(MR)过度激活的有害后果之一。皮肤炎症和血管生成在MR阻断的益处中的作用尚不清楚。 C57BL6小鼠经皮质醇氯倍他索局部处理后制成皮肤创面。伤后5天分析局部阻断核磁共振对炎症、血管生成和创面巨噬细胞表型的影响。类似的实验也在髓系细胞MR基因缺失的小鼠身上进行。局部抑制核磁共振，通过消除糖皮质激素处理的小鼠皮肤的长期炎症，改善了伤口延迟愈合的情况。这一效应与使用Canrenoate治疗的创面中抗炎巨噬细胞与促炎巨噬细胞的比率较高有关。此外，MR阻断导致促血管生成因子的表达上调，并改善了糖皮质激素预处理皮肤伤口中受损的血管生成。最后，髓系细胞表达MR的缺失重现了局部药物MR阻滞剂的益处。髓系盐皮质激素受体调节糖皮质激素损伤创面的真皮血管生成和炎症反应图片来源: https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.15932 综上所述，本研究结果表明，MR持续的GC刺激是延长效应的原因，MR阻滞剂可以治愈这种效应。在此，研究者重点研究了MR信号在炎症步骤中的主要作用，以及在皮质醇诱导的小鼠伤口延迟愈合过程中发生的受损血管变化。这些结果表明，在受影响的患者中，局部使用MR抑制剂也可以在类似的情况下有效。重要的是，研究者发现髓系MR在促进局部炎症中起关键作用，MR拮抗作用促进抗炎巨噬细胞极化和真皮血管生成，从而促进组织修复。因此，局部使用MR拮抗剂可能代表着一种实用的未来工具，可以帮助许多患者抱怨GC治疗导致的愈合延迟。（生物谷 Bioon.com）参考文献 Van Tuan Nguyen et al. Myeloid mineralocorticoid receptor regulates dermal angiogenesis and inflammation in glucocorticoid-induced impaired wound healing. Br J Pharmacol. 2022 Jul 21. doi: 10.1111/bph.15932.

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外链

KEGG	Wiki	ATC	Drug Bank
D01943	坎利酸钾	C03DA02	DB09015

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适应症	国家/地区	公司	日期
急性充血性心力衰竭	日本	Pfizer Japan, Inc.	1990-01-18
水肿	日本	Pfizer Japan, Inc.	1990-01-18
心源性水肿	日本	Pfizer Japan, Inc.	1990-01-18
醛固酮增多症	日本	Pfizer Japan, Inc.	1990-01-18