The blood-brain barrier (BBB) limits drug delivery to the central nervous system. When combined with microbubbles, ultrasound can transiently permeate blood vessels in the brain. This approach, which can be referred to as sonoporation or sonopermeabilization, holds significant promise for shuttling large therapeutic molecules, such as antibodies, growth factors and nanomedicine formulations, across the BBB. We here describe the basic principles of BBB permeation using ultrasound and microbubbles, and we summarize several (pre-) clinical studies showing the potential of BBB opening for improving the treatment of cancer and neurodegenerative disorders.
We aimed to assess the correlation between docosahexaenoic acid (DHA) dietary intake and the plasma, erythrocyte and breast milk DHA concentrations in lactating women residing in the coastland, lakeland and inland areas of China. A total of 408 healthy lactating women (42 ± 7 days postpartum) were recruited from four hospitals located in Weihai (coastland), Yueyang (lakeland) and Baotou (inland) city. The categories of food containing DHA, the average amount consumed per time and the frequency of consumption in the past month were assessed by a tailored DHA food frequency questionnaire, the DHA Intake Evaluation Tool (DIET). DHA dietary intake (mg/day) was calculated according to the Chinese Food Composition Table (Version 2009). In addition, fasting venous blood (5 mL) and breast milk (10 mL) were collected from lactating women. DHA concentrations in plasma, erythrocyte and breast milk were measured using capillary gas chromatography, and were reported as absolute concentration (μg/mL) and relative concentration (weight percent of total fatty acids, wt. %). Spearman correlation coefficients were used to assess the correlation between intakes of DHA and its concentrations in biological specimens. The study showed that the breast milk, plasma and erythrocyte DHA concentrations were positively correlated with DHA dietary intake; corresponding correlation coefficients were 0.36, 0.36 and 0.24 for relative concentration and 0.33, 0.32, and 0.18 for absolute concentration (p < 0.05). The median DHA dietary intake varied significantly across areas (p < 0.05), which was highest in the coastland (24.32 mg/day), followed by lakeland (13.69 mg/day), and lowest in the inland (8.84 mg/day). The overall relative and absolute DHA concentrations in breast milk were 0.36% ± 0.23% and 141.49 ± 107.41 μg/mL; the concentrations were significantly lower in inland women than those from coastland and lakeland. We conclude that DHA dietary intake is positively correlated with DHA concentrations in blood and breast milk in Chinese lactating women, suggesting that the tailored DHA food frequency questionnaire, DIET, is a valid tool for the assessment of DHA dietary intake.
The solubility data of diphenoxylate in pure solvents of water, methanol, ethanol, acetone, acetonitrile, 2-propanol were measured within the temperature range of 293.15−318.15 K by a static analytical method under atmospheric pressure. Several commonly used thermodynamic models, including the ideal solution model, the modified Apelblat equation and the Buchowski-Ksiazaczak λh equation, were applied to correlate the experimental solubility data. The experimental results show that the solubility increases with the increasing temperature, and the highest solubility is in methanol, the lowest in pure water. Results of these measurements were well-correlated with the three equations above, but the modified Apelblat equation is more suitable in regressing the solubility data of diphenoxylate. Through the Van't Hoff equation, the enthalpy and the entropy in different solvents can be calculated.
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