药物化学

The control of permeation is essential for the topical application of lotions, creams, and ointments, and the toxicological and risk assessment of materials from environmental and occupational hazards. This study developed a three-dimensional quantitative structure-activity relationship (3DQSAR) model to predict permeation of a variety of 210 compounds through human skin. Molecular descriptors were computed using a GRid Independent Descriptors (GRIND) approach. After variable selection via the genetic algorithm method, the 118 selected descriptors were correlated with skin permeability constants by PLS regression and support vector machine (SVM). Partial least squares regression (PLSR) and support vector regression (SVR) are two popular Chemometrics models that are being subjected to a comparative study in the presented work. Kennard-Stone algorithm was employed to split data set to a training set of 150 molecules and a test set of 60 molecules. Genetic algorithm (GA), as an influential linear tool, was used to certain the best and interpretative subset of variables for the predictive model structure. The best results were obtained by PLS regression with the correlation coefficient of R²=0.77 and SVM regression with the correlation R²=0.79. This strategy led to a final 3DQSAR model that presented Q²=0.61 and R² pred=0.73. The obtained results revealed that the hydrogen bonding donor and hydrogen bonding acceptor of investigated compounds dramatically influences their ability to penetrate through human skin. Furthermore, it was found that permeability was enhanced by increasing hydrophobicity and lowered with increasing molecular weight.

Background: This study compared the effects of Propofol and Sevoflurane anesthesia on the stabilization of acid-base values and hemodynamic parameters during one lung ventilation (OLV).

Methods: Patients with OLV were randomized two groups: the Propofol group (Group P, n=23) and the Sevoflurane group (Group S, n=23). In Group P, patients were induced and maintained with Propofol. In Group S, patients were induced with Propofol and maintained with Sevoflurane. Blood samples were obtained one minute before OLV (t₁) and 1, 2 hours (t₂, t₃) after OLV. Hemodynamic values were recorded at patients entered operation room (T₁); one minute before intubation (T₂); 1, 3, and 5 minutes after intubation (T₃, T₄, T₅); one minute before OLV (T₆); and 1, 2 hours after OLV (T₇, T₈).

Results: There were significant differences between different time points in pH value, base excess, and bicarbonate (P<0.001). The values of pH, base excess and bicarbonate in two groups both tended to reduce progressively from t₁ to t₃. There were no significant differences between the groups at all of the time points. There were significant differences between the different time points in terms of mean arterial pressure and heart rate (P<0.001), more patients in Group P received Nicardipine for hypertension (P<0.001). However, there were no significant intergroup differences.

Conclusions: The duration of one lung ventilation, anesthesia and operation, rather than the anaesthetic used, are key factors in maintaining acid-base balance during OLV. Sevoflurane anesthesia is superior to Propofol anesthesia in avoiding the fluctuation of hemodynamic parameters.