LitCovid-sentences  

PMC:7161517 / 19553-23121 JSONTXT 12 Projects

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Id Subject Object Predicate Lexical cue
T123 0-16 Sentence denotes ACE2 and Ang1-7:
T124 17-32 Sentence denotes Clinical Trials
T125 33-168 Sentence denotes ACE2 regulates RAS signaling by reducing Ang II/AT1 receptor signaling and by activating the ACE2/Ang1-7/Mas counterregulatory pathway.
T126 169-337 Sentence denotes Thus far, only a few pilot clinical studies have been conducted using rhACE2 in acute respiratory distress syndrome (ARDS), sepsis, and pulmonary arterial hypertension.
T127 338-469 Sentence denotes Multiple murine studies demonstrated rhACE2 modulates the RAS pathway, although it is unclear if these effects translate to humans.
T128 470-847 Sentence denotes A clinical study (Safety and Tolerability Study of APN01 [Recombinant Human Angiotensin Converting Enzyme 2]; NCT00886353) that assessed the pharmacokinetics and pharmacodynamics of soluble rhACE2 treatment in healthy volunteers with no known comorbidities showed a decrease in plasma Ang1-8 and increased Ang1-7 and Ang1-5 with no effect on blood pressure and heart rate (54).
T129 848-899 Sentence denotes Common side effects included diarrhea and headache.
T130 900-1021 Sentence denotes No antibodies to rhACE2 developed, which suggested there was no elicit immune response to single or repeated dosing (54).
T131 1022-1093 Sentence denotes Further studies investigating the immunogenicity of rhACE are required.
T132 1094-1179 Sentence denotes Serum levels of ACE and Ang II are elevated in patients with ARDS and sepsis (55,56).
T133 1180-1584 Sentence denotes Studies focused on microvascular dysfunction in sepsis showed that the degree of elevation in plasma renin and Ang II were correlated with the extent of organ failure and the degree of microvascular dysfunction, especially in patients who received exogenous vasoconstrictors (56); there was also a negative correlation between re-oxygenation rates and both concentrations of plasma renin and Ang II (56).
T134 1585-1886 Sentence denotes In a pilot clinical trial (Safety, Tolerability, PK and PD of GSK2586881 in Patients With Acute Lung Injury; NCT01597635), patients with ARDS who were treated with rhACE2 exhibited decreased plasma Ang II and elevated plasma Ang 1-7 and surfactant protein-D, which is involved in innate immunity (57).
T135 1887-2049 Sentence denotes IL-6 concentrations in treated patients were also reduced, albeit statistically insignificantly, which was due to intrasubject variability and baseline imbalance.
T136 2050-2210 Sentence denotes Although rhACE2 attenuated RAS mediators, infusions of the medication did not show improvement in physiological or clinical measures of ARDs in this study (57).
T137 2211-2382 Sentence denotes An additional pilot study (NCT101884051) investigated the effects of rhACE2 in human pulmonary arterial hypertension, which is characterized by reduced ACE2 activity (58).
T138 2383-2610 Sentence denotes Treatment with rhACE2 showed improved cardiac output that coincided with maximum suppression of plasma cytokines and reduction in nitrotyrosine levels, improved peripheral vascular resistance, and improved renal perfusion (58).
T139 2611-2681 Sentence denotes Ongoing clinical studies assessing the modulation of RAS axis include:
T140 2682-2896 Sentence denotes 1) the assessment of the relative activity of ACE and ACE2 in patients with diabetes following treatment with candesartan (Non-Insulin Dependent Diabetes Mellitus [NIDDM] and Angiotensin Converting Enzyme 2 [ACE2]:
T141 2897-3215 Sentence denotes Diabetic Patients Treated With Antihypertensive Drugs; NCT00192803); and 2) the overexpression of ACE2/Ang 1-7 in cardiac progenitor cells to assess for enhancement in reparative function and the potential to attenuate myocardial ischemia−induced cardiac damage (Cardiovascular Disease Protection Tissue; NCT02348515).
T142 3216-3422 Sentence denotes It is evident that targeting the ACE2/Ang1-7/Mas axis is going to be interesting in clinical settings because of the observed cardioprotective effects in the in vivo murine and in vitro cell culture models.
T143 3423-3568 Sentence denotes However, further investigation is required to demonstrate whether these favorable experimental effects could be translated into clinical benefit.