DO-2 is a highly selective MNNG HOS transforming (MET) inhibitor. This deuterated drug is thought to diminish the formation of the Aldehyde Oxidase 1 inactive metabolite M3. For various reasons, quantification of DO-2 and its metabolites M3 and DO-5 is highly relevant. In this study, we present an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method to quantify DO-2, M3 and DO-5. Rolipram served as the internal standard. Aliquots of 25 µL were mixed with 100 µL internal standard consisting of 10 ng/mL rolipram in acetonitrile. Separation of the analytes was achieved on an Acquity UPLC ® HSS T3 column, utilizing gradient elution with water/formic acid and acetonitrile/formic acid at a flow-rate of 0.400 mL/min. Calibration curves were linear in the range of 1.00 - 1000 ng/mL for DO-2 and DO-5, and 2.00 - 2000 ng/mL for M3 in human plasma. The within-run and between-run precisions of DO-2, DO-5 and M3, also at the level of the LLQ, were within 12.1%, while the accuracy ranged from 89.5 to 108.7%. All values for accuracy, within-run and between-run precisions met the criteria set by the Food and Drug Administration. The method was effectively employed in the analysis of samples obtained from a clinical trial.

18 Feb 2022·European Journal of Cardio-Thoracic SurgeryQ2 · MEDICINE

Critical oxygen delivery threshold during cardiopulmonary bypass in older cardiac surgery patients with increased frailty risk

Q2 · MEDICINE

Article

Author: Noordzij, Peter G ; Verwijmeren, Lisa ; Schreurs, Inge A A M ; Smoor, Rosa M ; van Dongen, Eric P A ; Vernooij, Lisette M ; van Klei, Wilton A

Abstract OBJECTIVESOlder patients have a higher cardiac surgery-associated acute kidney injury (CSA-AKI) related mortality. Low oxygen delivery (DO2) during cardiopulmonary bypass (CPB) is a risk factor for CSA-AKI, but critical DO2 thresholds for older patients are unknown. This study investigated critical DO2 thresholds for CSA-AKI in patients ≥70 years undergoing on-pump cardiac surgery.METHODSPatients were enrolled from July 2015 until August 2017. CPB data from 432 patients were collected, and DO2 values were calculated per minute. The primary outcome was CSA-AKI. The association between DO2 and CSA-AKI was analysed with multivariable regression analysis. Multiple DO2 thresholds were analysed. The association between CSA-AKI and the area below the DO2 thresholds (DO2 deficit) was evaluated, as was the association between frailty and CSA-AKI.RESULTSCSA-AKI occurred in 63 (14.6%) patients. Mean and nadir (lowest) DO2 values were lower in patients with CSA-AKI (283 vs 312 ml/min/m2; P-value <0.001 and 238 vs 270 ml/min/m2; P-value <0.001, respectively). The adjusted relative risk for CSA-AKI was 1.006 [99% confidence interval (CI) 1.001–1.012] per ml/min/m2 nadir DO2 decrease. The critical DO2 threshold was 270 ml/min/m2 [adjusted relative risk 2.06 (99% CI 1.33–2.80)]. The DO2 deficit below 270 ml/min/m2 was associated with CSA-AKI [adjusted relative risk 2.84 (99% CI 1.87–3.81)]. No association between frailty and CSA-AKI was found (P = 0.82).CONCLUSIONSLow DO2 increased the risk for CSA-AKI in older patients who had cardiac surgery. A critical DO2 threshold of 270 ml/min/m2 was applicable for frail and non-frail patients. The efficacy of a DO2 >270 ml/min/m2 to reduce CSA-AKI in older patients needs further evaluation.

25 Jul 2019·Investigative Opthalmology & Visual ScienceQ2 · MEDICINE

Alterations in Retinal Oxygen Delivery, Metabolism, and Extraction Fraction During Bilateral Common Carotid Artery Occlusion in Rats

Q2 · MEDICINE

ArticleOA

Author: Shahidi, Mahnaz ; Burford, James ; Farzad, Shayan ; Karamian, Preny ; Blair, Norman P.

PurposeThe purpose of the current study was to investigate alterations in retinal oxygen delivery, metabolism, and extraction fraction and elucidate their relationships in an experimental model of retinal ischemia.MethodsWe subjected 14 rats to permanent bilateral common carotid artery occlusion using clamp or suture ligation, or they underwent sham procedure. Within 30 minutes of the procedure, phosphorescence lifetime imaging was performed to measure retinal vascular oxygen tension and derive arterial and venous oxygen contents, and arteriovenous oxygen content difference. Fluorescent microsphere and red-free retinal imaging were performed to measure total retinal blood flow. Retinal oxygen delivery rate (DO2), oxygen metabolism rate (MO2), and oxygen extraction fraction (OEF) were calculated.ResultsDO2 and MO2 were lower in ligation and clamp groups compared to the sham group, and also lower in the ligation group compared to the clamp group (P ≤ 0.05). OEF was higher in the ligation group compared to clamp and sham groups (P ≤ 0.03). The relationships of MO2 and OEF with DO2 were mathematically modeled by exponential functions. With moderate DO2 reductions, OEF increased while MO2 minimally decreased. Under severe DO2 reductions, OEF reached a maximum value and subsequently MO2 decreased with DO2.ConclusionsThe findings improve knowledge of mechanisms that can maintain MO2 and may clarify the pathophysiology of retinal ischemic injury.

100 Deals associated with DO-2

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 1	BE	DeuterOncology SAStartup	20 Dec 2022
Non-Small Cell Lung Cancer	Phase 1	FR	DeuterOncology SAStartup	20 Dec 2022
Non-Small Cell Lung Cancer	Phase 1	NL	DeuterOncology SAStartup	20 Dec 2022
Non-Small Cell Lung Cancer	Phase 1	BE	DeuterOncology SAStartup	20 Dec 2022
Refractory Malignant Solid Neoplasm	Phase 1	FR	DeuterOncology SAStartup	20 Dec 2022
Refractory Malignant Solid Neoplasm	Phase 1	NL	DeuterOncology SAStartup	20 Dec 2022
Refractory Malignant Solid Neoplasm	Phase 1	BE	DeuterOncology SAStartup	20 Dec 2022
small cell carcinoma non	Phase 1	NL	DeuterOncology SAStartup	20 Dec 2022
small cell carcinoma non	Phase 1	FR	DeuterOncology SAStartup	20 Dec 2022
small cell carcinoma non	Phase 1	BE	DeuterOncology SAStartup	20 Dec 2022

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