12 research outputs found

    Synthesis and evaluation of nitrogen-containing derivatives of 3,11-dioxo-olean-12-en-30-oic acid against HIV-1 protease

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    Thirteen nitrogen-containing derivatives of 3,11-dioxo-olean-12-en-30-oic acid were synthesised by introducing various amino acids and nitrogen-containing heterocyclic groups at the 30-carboxyl group, starting from 18β-glycyrrhetinic acid. Among the 13 derivatives, 10 exhibited inhibitory activity against HIV-1 PR, with IC50 values ranging from 0.19 to 0.94 mM. Notably, derivatives 2, 3 and 5 displayed relatively moderate inhibitory activity, with IC50 values below 0.24 mM. Molecular docking studies provided further insights into the interaction between derivatives (2, 3 and 5) and the active sites of HIV-1 PR. The results revealed favourable hydrophobic-hydrophobic and hydrogen bonding interactions, with docking scores ranging from −6.22 to −7.00 and glide emodel values from −62.9 to −48.6 (kcal/mol). These findings underscore the potential of derivatives 2, 3 and 5 as promising candidates for the development of HIV-1 PR inhibitors.</p

    Experimental Protocol.

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    <p>Group Ia = non-arrested with chest compressions (to a depth of 5cm); Group Ib = non-arrested with chest compressions (to a depth of 3cm); Group IIa = arrested with chest compressions (to a depth of 5cm) only; Group IIb = arrested with chest compressions (to a depth of 3cm) only; Group IIIa = compressions to a depth of 5cm continued after ROSC; Group IIIb = compressions to a depth of 3cm continued after ROSC; Group IIIc = chest compressions stopped after ROSC; ROSC = return of spontaneous circulation; VF = ventricular fibrillation; CC = chest compressions; DF = defibrillation; SC = stop compressions.</p

    Hemodynamic values in arrested animals with chest compressions after ROSC.

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    <p>Group IIIa = compressions to a depth of 5cm continued after ROSC; Group IIIb = compressions to a depth of 3cm continued after ROSC; Group IIIc = chest compressions stopped after ROSC; CC1 = chest compressions to a depth of 5cm; DF = ROSC after defibrillation; CC2 = chest compressions in Group IIIa (5cm) and IIIb (3cm) and the same time in Group IIIc; SC = stop compressions in Group IIIa and IIIb and the same time in Group IIIc; ROSC = return of spontaneous circulation; HR = heart rate; SAP = systolic arterial pressure; DAP = diastolic arterial pressure; MAP = mean arterial pressure; CPP = coronary perfusion pressure. *: statistically significant difference between treatment groups.</p

    Hemodynamic values in non-arrested animals with chest compressions.

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    <p>CC = chest compressions; AC = after compressions. Group Ia = non-arrested with chest compressions (to a depth of 5cm); Group Ib = non-arrested with chest compressions (to a depth of 3cm); HR = heart rate; SAP = systolic arterial pressure; DAP = diastolic arterial pressure; MAP = mean arterial pressure; CPP = coronary perfusion pressure.*: statistically significant difference between treatment groups.</p

    Pulse Oximetry: A Non-Invasive, Novel Marker for the Quality of Chest Compressions in Porcine Models of Cardiac Arrest

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    <div><p>Objective</p><p>Pulse oximetry, which noninvasively detects the blood flow of peripheral tissue, has achieved widespread clinical use. We have noticed that the better the quality of cardiopulmonary resuscitation (CPR), the better the appearance of pulse oximetry plethysmographic waveform (POP). We investigated whether the area under the curve (AUC) and/or the amplitude (Amp) of POP could be used to monitor the quality of CPR.</p><p>Design</p><p>Prospective, randomized controlled study.</p><p>Setting</p><p>Animal experimental center in Peking Union Medical Collage Hospital, Beijing, China.</p><p>Subjects</p><p>Healthy 3-month-old male domestic swine.</p><p>Interventions</p><p>34 local pigs were enrolled in this study. After 4 minutes of untreated ventricular fibrillation, animals were randomly assigned into two resuscitation groups: a “low quality” group (with a compression depth of 3cm) and a “high quality” group (with a depth of 5cm). All treatments between the two groups were identical except for the depth of chest compressions. Hemodynamic parameters [coronary perfusion pressure (CPP), partial pressure of end-tidal carbon dioxide (P<sub>ET</sub>CO<sub>2</sub>)] as well as AUC and Amp of POP were all collected and analyzed.</p><p>Measurements and Findings</p><p>There were statistical differences between the “high quality” group and the “low quality” group in AUC, Amp, CPP and P<sub>ET</sub>CO<sub>2</sub> during CPR (P<0.05). AUC, Amp and CPP were positively correlated with P<sub>ET</sub>CO<sub>2</sub>, respectively (P<0.01). There was no statistical difference between the heart rate calculated according to the POP (F<sub>CPR</sub>) and the frequency of mechanical CPR at the 3<sup>rd</sup> minute of CPR. The <i>F</i><sub><i>CPR</i></sub> was lower than the frequency of mechanical CPR at the 6<sup>th</sup> and the 9<sup>th</sup> minute of CPR.</p><p>Conclusions</p><p>Both the AUC and Amp of POP correlated well with CPP and P<sub>ET</sub>CO<sub>2</sub> in animal models. The frequency of POP closely matched the CPR heart rate. AUC and Amp of POP might be potential noninvasive quality monitoring markers for CPR.</p></div

    Physiological parameters at baseline.

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    <p>Note: Amp and AUC were calculated as the average of the data collected 30s before the detect time.</p><p>No statically significant differences were detected in any parameters between the two groups.</p><p>LQ group: low quality resuscitation group; HQ group: high quality resuscitation group; HR: heart rate; CPP: coronary perfusion pressure; P<sub>ET</sub>CO<sub>2</sub>: pressure of end-tidal carbon dioxide; AUC: area of under the curve; Amp: amplitude of POP; PVA: Pulse Oximeter Voltage Amplitude; PVPG: Pulse Oximeter Voltage Plehtysmography.</p><p>Physiological parameters at baseline.</p

    Physiological parameters during resuscitation.

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    <p>Note: Amp and AUC were calculated as the average of the data collected 30s before the detect time.</p><p>PVA: Pulse Oximeter Votage Amplitude; PVPG: Pulse Oximeter Voltage Plehtysmography</p><p>Physiological parameters during resuscitation.</p
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