scholarly journals Vasospastic angina: pathophysiology and clinical significance

2020 ◽  
Vol 19 (1) ◽  
pp. 99-105
Author(s):  
B. I. Geltser ◽  
M. M. Tsivanyuk ◽  
V. N. Kotelnikov ◽  
R. S. Karpov
Keyword(s):  
Kinase Inhibitors ◽  
Magnesium Deficiency ◽  
Coronary Artery Spasm ◽  
Rho Kinase ◽  
Diagnosis And Treatment ◽  
Vasospastic Angina ◽  
Coronary Smooth Muscle ◽  
Provocation Tests ◽  
Life Threatening ◽  
Long Acting

The review discusses an analysis of the literature on various aspects of the pathogenesis, diagnosis and treatment of vasospastic angina (VA). Data on the prevalence of coronary artery spasm (CAS) in various populations, as well as risk factors and triggers, are presented. We considered pathophysiological mechanisms of CAS, including hyperreactivity of coronary smooth muscle cells, endothelial dysfunction, nonspecific inflammation, oxidative stress, magnesium deficiency, autonomic imbalance, etc. The relationship of CAS with coronary atherosclerosis and thrombosis is emphasized. Modern recommendations for the diagnosis and treatment of VA are presented. Invasive verification of CAS is performed by pharmacological provocation tests with certain contraindications. Calcium antagonists and their combination with long-acting nitrates play a key role in the treatment of VA. Medications with a prospect for use in VA are Rho-kinase inhibitors, ATP-sensitive potassium channel activators, alpha-1 blockers. The management of patients with refractory VA and the prospects for endovascular treatment are discussed. It was noted that patients with multi-vessel VA are more likely to develop life-threatening arrhythmias and sudden death.

scholarly journals Vasospastic angina: pathophysiology and clinical significance

2020 ◽  
Vol 19 (1) ◽  
pp. 99-105
Author(s):  
B. I. Geltser ◽  
M. M. Tsivanyuk ◽  
V. N. Kotelnikov ◽  
R. S. Karpov
Keyword(s):  
Kinase Inhibitors ◽  
Magnesium Deficiency ◽  
Coronary Artery Spasm ◽  
Rho Kinase ◽  
Diagnosis And Treatment ◽  
Vasospastic Angina ◽  
Coronary Smooth Muscle ◽  
Provocation Tests ◽  
Life Threatening ◽  
Long Acting

The review discusses an analysis of the literature on various aspects of the pathogenesis, diagnosis and treatment of vasospastic angina (VA). Data on the prevalence of coronary artery spasm (CAS) in various populations, as well as risk factors and triggers, are presented. We considered pathophysiological mechanisms of CAS, including hyperreactivity of coronary smooth muscle cells, endothelial dysfunction, nonspecific inflammation, oxidative stress, magnesium deficiency, autonomic imbalance, etc. The relationship of CAS with coronary atherosclerosis and thrombosis is emphasized. Modern recommendations for the diagnosis and treatment of VA are presented. Invasive verification of CAS is performed by pharmacological provocation tests with certain contraindications. Calcium antagonists and their combination with long-acting nitrates play a key role in the treatment of VA. Medications with a prospect for use in VA are Rho-kinase inhibitors, ATP-sensitive potassium channel activators, alpha-1 blockers. The management of patients with refractory VA and the prospects for endovascular treatment are discussed. It was noted that patients with multi-vessel VA are more likely to develop life-threatening arrhythmias and sudden death.

scholarly journals Vasospastic angina: pathophysiology and clinical significance

2020 ◽  
Vol 19 (1) ◽  
pp. 99-105
Author(s):  
B. I. Geltser ◽  
M. M. Tsivanyuk ◽  
V. N. Kotelnikov ◽  
R. S. Karpov
Keyword(s):  
Kinase Inhibitors ◽  
Magnesium Deficiency ◽  
Coronary Artery Spasm ◽  
Rho Kinase ◽  
Diagnosis And Treatment ◽  
Vasospastic Angina ◽  
Coronary Smooth Muscle ◽  
Provocation Tests ◽  
Life Threatening ◽  
Long Acting

The review discusses an analysis of the literature on various aspects of the pathogenesis, diagnosis and treatment of vasospastic angina (VA). Data on the prevalence of coronary artery spasm (CAS) in various populations, as well as risk factors and triggers, are presented. We considered pathophysiological mechanisms of CAS, including hyperreactivity of coronary smooth muscle cells, endothelial dysfunction, nonspecific inflammation, oxidative stress, magnesium deficiency, autonomic imbalance, etc. The relationship of CAS with coronary atherosclerosis and thrombosis is emphasized. Modern recommendations for the diagnosis and treatment of VA are presented. Invasive verification of CAS is performed by pharmacological provocation tests with certain contraindications. Calcium antagonists and their combination with long-acting nitrates play a key role in the treatment of VA. Medications with a prospect for use in VA are Rho-kinase inhibitors, ATP-sensitive potassium channel activators, alpha-1 blockers. The management of patients with refractory VA and the prospects for endovascular treatment are discussed. It was noted that patients with multi-vessel VA are more likely to develop life-threatening arrhythmias and sudden death.

scholarly journals An update on long-acting therapies in chronic sight-threatening eye diseases of the posterior segment: AMD, DMO, RVO, uveitis and glaucoma

Eye ◽  
2022 ◽  
Author(s):  
Faruque Ghanchi ◽  
Rupert Bourne ◽  
Susan M. Downes ◽  
Richard Gale ◽  
Christina Rennie ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Late Phase ◽  
Rho Kinase ◽  
Diabetic Macular Oedema ◽  
Negative Consequences ◽  
Regular Treatment ◽  
Anti Vegf ◽  
Age Related ◽  
Phase Development ◽  
Long Acting

AbstractIn the real-world setting, there is suboptimal compliance with treatments that require frequent administration and assessment visits. This undertreatment frequently has negative consequences in eye disease and carries a real risk to vision. For example, patients with glaucoma risk progression of visual loss even with a small number of missed doses, and patients with neovascular age-related degeneration (nAMD) who fail to attend a bi-monthly clinic appointment to receive an intravitreal anti-vascular endothelial growth factor (VEGF) drug injections may lose the initial vision gains in vision. Protracted regular treatment schedules represent a high burden not only for patients and families, but also healthcare professionals, systems, and ultimately society too. There has been a clear need for longer-acting therapies that reduce the frequency, and therefore the burden, of treatment interventions. Several longer-acting interventions for nAMD, diabetic macular oedema, retinal vein occlusion, uveitis and glaucoma have either been developed or are in late-phase development, some of which employ novel mechanisms of actions, and all of which of promise longer (≥3 month) treatment intervals. This review delivers an overview of anti-VEGF agents with longer durations of action, DARPins, bispecific anti-VEGF/Ang2 therapies, anti-PDGF and anti-integrin therapy, Rho-kinase inhibitors, the Port Delivery System, steroids, gene therapy for retina and uveitis, and for glaucoma, ROCK inhibitors, implants and plugs, and SLT laser and MIGS. The review also refers to the potential of artificial intelligence to tailor treatment efficacy with a resulting reduction in treatment burden.

scholarly journals Suppression of Coronary Artery Spasm by the Rho-Kinase Inhibitor Fasudil in Patients With Vasospastic Angina

Circulation ◽  
2002 ◽  
Vol 105 (13) ◽  
pp. 1545-1547 ◽  
Author(s):  
Akihiro Masumoto ◽  
Masahiro Mohri ◽  
Hiroaki Shimokawa ◽  
Lemmy Urakami ◽  
Makoto Usui ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Kinase Inhibitor ◽  
Coronary Artery Spasm ◽  
Rho Kinase ◽  
Vasospastic Angina ◽  
Rho Kinase Inhibitor

Abstract 14056: Prognostic Impact of Rho-kinase Activity in Circulating Leukocytes of Patients with Vasospastic Angina

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Taro Nihei ◽  
Jun Takahashi ◽  
Ryuji Tsuburaya ◽  
Kiyotaka Hao ◽  
Yuji Odaka ◽  
...  
Keyword(s):  
Kinase Activity ◽  
Coronary Artery Spasm ◽  
Rho Kinase ◽  
Vasospastic Angina ◽  
Channel Blockers ◽  
Prognostic Impact ◽  
Linear Regression Models ◽  
Cardiac Events ◽  
Kinase Substrate ◽  
Kaplan Meier

Background: Rho-kinase plays a central role in the pathogenesis of coronary artery spasm. We have recently demonstrated that Rho-kinase activity in circulating leukocytes is a useful biomarker for diagnosis and disease activity assessment of vasospastic angina (VSA). However, its prognostic impact in VSA patients remains to be examined. Methods: We prospectively enrolled 174 consecutive VSA patients (M/F 116/58, 62±12 [SD] yrs) and 53 non-VSA patients (M/F 32/21, 62±15 yrs) and followed them for 14±9 months. At the enrollment, Rho-kinase activity in circulating leukocytes (the ratio of phosphorylated/total form of myosin binding subunit, a Rho-kinase substrate) was measured. The primary endpoint was major adverse cardiac events (MACE). Results: Baseline Rho-kinase activity was significantly higher in VSA than in non-VSA patients (1.20±0.33 vs. 1.07±0.21, P<0.01) and all VSA patients were treated with calcium channel blockers. During the follow-up period, MACE occurred in 9 VSA patients (5.2%) but none in non-VSA patients. Baseline Rho-kinase activity was significantly higher in VSA patients with MACE than in those without it (1.33±0.13 vs. 1.20±0.33, P<0.001). Importantly, when we divided VSA patients into 2 groups by a median value of baseline Rho-kinase activity, Kaplan-Meier survival analysis showed a significantly worse prognosis in VSA patients with high Rho-kinase activity (p-MBS/t-MBS ≥1.20) ( Figure ). Univariate linear regression models showed that there was no association between established prognostic factors of VSA (e.g. history of out-of-hospital cardiac arrest, current smoking, angina at rest, significant organic stenosis and β-blocker use) and baseline increased levels of Rho-kinase activity. Conclusions: These results indicate that increased Rho-kinase activity in circulating leukocytes may be a useful and independent biomarker for long-term prognosis of VSA patients.

Probing Cellular Outcomes Using Heterobivalent Constructs

2019 ◽  
Author(s):  
Rohit Bhadoria ◽  
Kefeng Ping ◽  
Christer Lohk ◽  
Ivar Järving ◽  
Pavel Starkov
Keyword(s):  
Cell Viability ◽  
Small Molecules ◽  
Cellular Uptake ◽  
Kinase Inhibitors ◽  
Rho Kinase ◽  
Intracellular Delivery ◽  
Rho Kinase Inhibitors

<div> <div> <div> <p>Conjugation techniques are central to improving intracellular delivery of bioactive small molecules. However, tracking and assessing the overall biological outcome of these constructs remains poorly understood. We addressed this issue by having developed a focused library of heterobivalent constructs based on Rho kinase inhibitors to probe various scenarios. By comparing induction of a phenotype of interest vs. cell viability vs. cellular uptake, we demonstrate that such conjugates indeed lead to divergent cellular outcomes. </p> </div> </div> </div>

scholarly journals Lidocaine: A Local Anesthetic, Its Adverse Effects and Management

Medicina ◽  
2021 ◽  
Vol 57 (8) ◽  
pp. 782
Author(s):  
Entaz Bahar ◽  
Hyonok Yoon
Keyword(s):  
Adverse Effects ◽  
Local Anesthetic ◽  
Local Anesthetics ◽  
Adverse Reactions ◽  
Rapid Diagnosis ◽  
Diagnosis And Treatment ◽  
Allergic Reactions ◽  
Life Threatening

The most widely used medications in dentistry are local anesthetics (LA), especially lidocaine, and the number of recorded adverse allergic responses, particularly of hazardous responses, is quite low. However, allergic reactions can range from moderate to life-threatening, requiring rapid diagnosis and treatment. This article serves as a review to provide information on LA, their adverse reactions, causes, and management.

scholarly journals Neovascular Macular Degeneration: A Review of Etiology, Risk Factors, and Recent Advances in Research and Therapy

2021 ◽  
Vol 22 (3) ◽  
pp. 1170
Author(s):  
Arunbalaji Pugazhendhi ◽  
Margaret Hubbell ◽  
Pooja Jairam ◽  
Balamurali Ambati
Keyword(s):  
Risk Factors ◽  
Macular Degeneration ◽  
Kinase Inhibitors ◽  
Rho Kinase ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Gene Therapies ◽  
Rho Kinase Inhibitors ◽  
Age Related ◽  
Endothelial Growth Factor

Neovascular age-related macular degeneration (exudative or wet AMD) is a prevalent, progressive retinal degenerative macular disease that is characterized by neovascularization of the choroid, mainly affecting the elderly population causing gradual vision impairment. Risk factors such as age, race, genetics, iris color, smoking, drinking, BMI, and diet all play a part in nvAMD’s progression, with anti-vascular endothelial growth factor (anti-VEGF) therapy being the mainstay of treatment. Current therapeutic advancements slow the progression of the disease but do not cure or reverse its course. Newer therapies such as gene therapies, Rho-kinase inhibitors, and levodopa offer potential new targets for treatment.

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