Establishment of a single-point assay to evaluate the relationship of molecular structure and antiviral activity of cationic amphiphilic drugs

Author(s):  
Antonia-Patricia Gunesch
Perfusion ◽  
2020 ◽  
pp. 026765912095815
Author(s):  
J Trent Magruder ◽  
Alexandra Sperry ◽  
Pavan Atluri ◽  
Christian Bermudez ◽  
Edward Cantu ◽  
...  

Purpose: We sought to assess the relationship of intraoperative perfusion parameters while on cardiopulmonary bypass, including oxygen delivery (DO2), to the need for ECMO following orthotopic heart transplantation (OHT). Methods: We included all adult (>18 years old) OHTs performed at our institution since implementation of an electronic perfusion record (March 2019-February 2020). Multi-organ transplants were excluded. The primary outcome was the need for immediate venoarterial ECMO in the OR following OHT. Univariable statistics were computed across demographic, clinical, operative, and perfusion variables, including oxygen delivery (DO2) measured each minute. Results: Fifty-three OHT were included with a median age of 54 years (interquartile range, 45-61). The primary outcome occurred in eight patients (15.1%). A significantly greater proportion of patients requiring ECMO had ischemic cardiomyopathy (50.0% (4/8) vs. 15.6% (7/45), p = 0.02) and had preoperative ventricular assist devices (37.5% (3/8) vs. 8.9% (4/45), p = 0.03). Median bypass times were longer in the ECMO group (217 vs. 147 minutes, p = 0.001). Phenylephrine doses were nonsignificantly higher in ECMO patients (4.1 vs. 1.9 mg, p = 0.10). No significant differences were observed in single-point median DO2 (275 vs. 294 mL O2/min/m2 BSA, p = 0.17) and nadir DO2 (226 vs. 222, p = 0.94), but increasing time and depth of DO2 below a threshold of 300 mL O2/min/m2 BSA (i.e. area over the DO2 curve (AOC) but below threshold) was significantly associated with the need for postoperative ECMO (p = 0.04). Conclusion: This is the first study to examine the relationship of perfusion parameters, including oxygen delivery, to outcomes following heart transplantation. We note that DO2 < 300-AOC was significantly associated with the need for postoperative ECMO following heart transplant. Further study will clarify whether potential DO2 differences in patients who require post-OHT ECMO reflect vasoplegia, or a more causative relationship which might be leveraged to improve outcomes.


1971 ◽  
Vol 11 (1) ◽  
pp. 80
Author(s):  
R. J. Allen

The Queensland Department of Mines has undertaken stratigraphic drilling to assist petroleum exploration since 1965. The primary purpose was to obtain core for palynological and petrological study, in order to facilitate correlation of strata met in deep exploratory wells with the type sections of outcrop.To the end of October, 1970, 61 bores have been completed for a total of 50,473 feet (15,394 metres), an average depth of 827 feet (252 metres).Average drilling cost ranged from about $5 per foot at shallow depths to about $15 per foot towards the current maximum capacity of 4,000 feet (1,220 metres), total cost was of the order of $400,000.All holes were fully cored from about 50 feet (about 15 metres) to total depth. With minor exceptions, all drilling has been with NX equipment, giving a core approximately 1.7 inches (4.3 centimetres) in diameter. The core barrel is 10 feet (3 metres) long; it is recovered by the wireline method. On completion, most holes have been logged electrically and radiometrically (spontaneous potential, single-point resistivity and gamma-ray).Drilling lias been undertaken in sediments of the Surat, Bowen, Moreton and Ipswich Basins, and the Esk Rift. In the Surat Basin, complete sections of the Jurassic have been obtained on both the western and eastern flanks, and the Cretaceous has been sampled completely near the middle of the basin; in addition, the Injune Creek Group (Jurassic) is being investigated in some detail. In the Bowen Basin, representative material has been obtained from the Triassic units (Rewan, Clematis and Moolayember); the Permian on the eastern flank has been sampled completely in a Departmental coal-exploration project. In the Moreton Basin, a series of regional lines was drilled, partly in order to establish the relationship of the Bundamba Group to the Jurassic of the Surat Basin.One hole was drilled in the Ipswich Basin, to sample the upper part of the Triassic succession there.The program has been especially effective in providing material for palynological studies, both descriptive and stratigraphic, particularly in sandstone units. By this means, several important stratigraphic problems were resolved. For example, the type Wandoan Formation of Union-Kern-A.O.G. Wandoan 1 well was shown to be equivalent in age to the lower and middle Clematis Sandstone of outcrop, whereas the so-called Wandoan elsewhere in the basin was shown to be equivalent to the uppermost Clematis and lower Moolayember Formation of outcrop. Again, the drilling has confirmed the lithological correlation of the Precipice Sandstone of the Surat Basin with the Helidon Sandstone of the Moreton Basin, and the Evergreen Formation and Hutton Sandstone (which overlie the Precipice) with the Marburg Sandstone (which overlies the Helidon); the remarkably persistent oolite marker in the Evergreen and Marburg has been shown to be of essentially the same age throughout.Extension of the project widely through the sedimentary basins of Queensland is warranted.Proposed work for 1971 includes drilling of the Permian on the western flank of the Bowen Basin, and of the Tertiary in the Hillsborough Basin.


2019 ◽  
Vol 20 (16) ◽  
pp. 4032 ◽  
Author(s):  
Bin Du ◽  
Maninder Meenu ◽  
Hongzhi Liu ◽  
Baojun Xu

β-glucan is a non-starch soluble polysaccharide widely present in yeast, mushrooms, bacteria, algae, barley, and oat. β-Glucan is regarded as a functional food ingredient due to its various health benefits. The high molecular weight (Mw) and high viscosity of β-glucan are responsible for its hypocholesterolemic and hypoglycemic properties. Thus, β-glucan is also used in the food industry for the production of functional food products. The inherent gel-forming property and high viscosity of β-glucan lead to the production of low-fat foods with improved textural properties. Various studies have reported the relationship between the molecular structure of β-glucan and its functionality. The structural characteristics of β-glucan, including specific glycosidic linkages, monosaccharide compositions, Mw, and chain conformation, were reported to affect its physiochemical and biological properties. Researchers have also reported some chemical, physical, and enzymatic treatments can successfully alter the molecular structure and functionalities of β-glucan. This review article attempts to review the available literature on the relationship of the molecular structure of β-glucan with its functionalities, and future perspectives in this area.


2020 ◽  
Vol 64 (8) ◽  
Author(s):  
Antonia P. Gunesch ◽  
Francisco J. Zapatero-Belinchón ◽  
Lukas Pinkert ◽  
Eike Steinmann ◽  
Michael P. Manns ◽  
...  

ABSTRACT Several cationic amphiphilic drugs (CADs) have been found to inhibit cell entry of filoviruses and other enveloped viruses. Structurally unrelated CADs may have antiviral activity, yet the underlying common mechanism and structure-activity relationship are incompletely understood. We aimed to understand how widespread antiviral activity is among CADs and which structural and physico-chemical properties are linked to entry inhibition. We measured inhibition of Marburg virus pseudoparticle (MARVpp) cell entry by 45 heterogeneous and mostly FDA-approved CADs and cytotoxicity in EA.hy926 cells. We analyzed correlation of antiviral activity with four chemical properties: pKa, hydrophobicity (octanol/water partitioning coefficient; ClogP), molecular weight, and distance between the basic group and hydrophobic ring structures. Additionally, we quantified drug-induced phospholipidosis (DIPL) of a CAD subset by flow cytometry. Structurally similar compounds (derivatives) and those with similar chemical properties but unrelated structures (analogues) to those of strong inhibitors were obtained by two in silico similarity search approaches and tested for antiviral activity. Overall, 11 out of 45 (24%) CADs inhibited MARVpp by 40% or more. The strongest antiviral compounds were dronedarone, triparanol, and quinacrine. Structure-activity relationship studies revealed highly significant correlations between antiviral activity, hydrophobicity (ClogP > 4), and DIPL. Moreover, pKa and intramolecular distance between hydrophobic and hydrophilic moieties correlated with antiviral activity but to a lesser extent. We also showed that in contrast to analogues, derivatives had antiviral activity similar to that of the seed compound dronedarone. Overall, one-quarter of CADs inhibit MARVpp entry in vitro, and antiviral activity of CADs mostly relies on their hydrophobicity yet is promoted by the individual structure.


2014 ◽  
Vol 905 ◽  
pp. 82-87 ◽  
Author(s):  
You Ji Tao ◽  
Gan Xin Jie ◽  
Xiao Dong Zhang ◽  
Li Fen Hu ◽  
Jian Peng ◽  
...  

A sorbitolum compound and an aryl amide compound were applied to prepare α-nucleated PP (α-PP) and β-nucleated PP (β-PP), respectively. Effects of UV irradiation on the molecular structure and tensile properties of pure PP, α-PP and β-PP were investigated. The relationship of tensile strength with carbonyl index was discussed. The change of relative content of β-modification in β-PP during photodegradation was examined by WAXD. The carbonyl index calculated from FTIR spectra arranged as α-PP > PP > β-PP, however, the tensile strength retention at the UV irradiation time of 792h arranged as PP > β-PP > α-PP. The relative content of β-crystal nearly unchanged during the photodegradation.


1970 ◽  
Vol 16 (12) ◽  
pp. 1303-1310 ◽  
Author(s):  
Edward T. Sheaff ◽  
Robert B. Stewart

Studies of the effect of interferon on the growth of Sindbis virus in cultures of chick embryo cells have shown that interferon is taken up by cells and that such uptake must occur before antiviral activity is observed. Evidence is presented here that the quantitative expression of antiviral activity is dependent on the amount of interferon that becomes cell associated.


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