Calcium-Regulated Protein Kinases Low Km cGMP Phosphodiesterases: Targets for Novel Antihypertensive Therapy

Author(s):  
Paul J. Silver ◽  
Edward D. Pagani ◽  
Wayne R. Cumiskey ◽  
Ronald L. Dundore ◽  
Alex L. Harris ◽  
...  
2018 ◽  
Vol 34 (2) ◽  
pp. 259-265 ◽  
Author(s):  
Hemant B Kardile ◽  
◽  
Vikrant ◽  
Nirmal Kant Sharma ◽  
Ankita Sharma ◽  
...  

2000 ◽  
Vol 41 (3) ◽  
pp. 339-348
Author(s):  
Sumino Hiroyuki ◽  
Nakamura Tetsuya ◽  
Kanda Tsugiyasu ◽  
Sakamaki Tetsuo ◽  
Sato Kunio ◽  
...  

2020 ◽  
Vol 7 (2) ◽  
pp. 205-211
Author(s):  
Kaynat Fatima ◽  
Syed Tasleem Raza ◽  
Ale Eba ◽  
Sanchita Srivastava ◽  
Farzana Mahdi

The function of protein kinases is to transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Many of these kinases are linked to the initiation and development of human cancer. The recent development of small molecule kinase inhibitors for the treatment of different types of cancer in clinical therapy has proven successful. Significantly, after the G-protein-coupled receptors, protein kinases are the second most active category of drug targets. Imatinib mesylate was the first tyrosine kinase inhibitor (TKI), approved for chronic myeloid leukemia (CML) treatment. Imatinib induces appropriate responses in ~60% of patients; with ~20% discontinuing therapy due to sensitivity, and ~20% developing drug resistance. The introduction of newer TKIs such as, nilotinib, dasatinib, bosutinib, and ponatinib has provided patients with multiple options. Such agents are more active, have specific profiles of side effects and are more likely to reach the necessary milestones. First-line treatment decisions must be focused on CML risk, patient preferences and comorbidities. Given the excellent result, half of the patients eventually fail to seek first-line treatment (due to discomfort or resistance), with many of them needing a third or even further therapy lines. In the present review, we will address the role of tyrosine kinase inhibitors in therapy for chronic myeloid leukemia.


Author(s):  
О.А. Радаева ◽  
А.С. Симбирцев

Цель - изучение сывороточных уровней LIF, sLIr и их соотношение с гемодинамическими параметрами (ЧСС, САД, ДАД, ПАД, ЦАД, срАД, УО, МОК, ОПСС, СПВ) и содержанием вазоактивных веществ (AT II, ET-1, NO, ADMA, SDMA, eNOS, iNOS, NT-proСNP, NT-proBNP) у пациентов с эссенциальной артериальной гипертензией (ЭАГ) II стадии. Методы: количество LIF, sLIF-R/gp190 и вазоактивные вещества в сыворотке определяли иммуноферментным методом. Результаты: у пациентов с ЭАГ II стадии вне зависимости от проведения гипотензивной терапии была более высокая концентрация LIF (7,54 (2,8) пг/мл, 7,5 (2,1) пг/мл), по сравнению с условно здоровыми - 1,25 (0,5) пг/мл, р<0,001. При этом у пациентов, не получавших гипотензивные препараты, увеличивался уровень sLIr - (5800 (1470 pg/ml)) по сравнению с больными на фоне гипотензивной терапии (4100 (1380) пг/мл, р<0,001) и условно здоровыми (3800 (1100) пг/мл, р<0,001). При уровне sLIF-R выше 4800 пг/мл обнаруживали связь с увеличением содержания в сыворотке iNOS, NT-proBNP, ADMA, SDMA, (r = 0,5-0,8, р<0,05-0,001) и уменьшением уровня eNOS (r = -0,56-0,86, р<0,05-0,001), что соответствует прогрессированию заболевания. Корреляции между LIF и указанными вазоактивными веществами выявлено не было, что дает основание предполагать, что sLIFr вызывает собственные патогенетические эффекты помимо антагонистической активности по отношению к LIF. Aim. To study levels of serum LIF and sLIF-R and their correlations with hemodynamic parameters (heart rate, systolic BP, diastolic BP, pulse pressure, central BP, mean BP, stroke volume, total peripheral resistance, and pulse wave velocity) and vasoactive substances (AT II, ET-1, NO, ADMA, SDMA, eNOS, iNOS, NT-proСNP, and NT-proBNP) in patients with stage II essential arterial hypertension (EAH). Methods. Serum levels of LIF and sLIF-R/gp190 were measured using ELISA in 180 patients with stage II ЕAН. Results: Patients with EAH II (with or without antihypertensive therapy) had higher serum levels of LIF (7.54 (2.8) pg/ml and 7.5 (2.1) pg/ml, respectively) compared to healthy individuals (1.25 (0.5) pg/ml), р<0.001. Patients not receiving a therapy had higher serum levels of sLIF-R (5800 (1470 pg/ml) than patients receiving antihypertensive drugs (4100 (1380) pg/ml, р<0.001) and healthy individual (3800 (1100) pg/ml, р<0.001). In patients with EAH, sLIF-R levels higher than 4800 pg/ml correlated with increases in iNOS, NT-proBNP, ADMA, and SDMA (r = 0.5-0.8, р<0.05-0.001) and decreases in eNOS (r = -0.56-0.86, р<0.05-0.001), which corresponded to disease progression. LIF did not show any significant correlations with these vasoactive substances, which suggested that sLIF-R exerted its own pathogenetic effects besides antagonizing LIF. Generally, this trend was typical for patients with EAH (II stage) without antihypertensive therapy.


2016 ◽  
Vol 18 (5) ◽  
pp. 36-42
Author(s):  
S.R. Giliarevskii ◽  
◽  
M.V. Golshmid ◽  
I.M. Kuzmina ◽  
G.Yu. Zakharova ◽  
...  

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