Functionalized Hyperbranched Polyethylenimines as Thermosensitive Drug Delivery Nanocarriers with Controlled Transition Temperatures.

The low critical solution temperature phase transition (Tc) that is exhibited by thermosensitive polymers is strongly dependent on polymer concentration, pH, ionic strength, as well as the presence of specific molecules or ions in solution. Therefore, polymers with Tc values above 37 °C that are useful for hyperthermia therapy are not readily available. In the present study, temperature-sensitive hyperbranched polyethylenimine derivatives were developed through stepwise functionalization with isobutylamide groups. Although factors such as the concentration of polymer, sodium chloride, phosphate ions, and pH considerably affect the transition temperature, it was possible to obtain a hyperbranched derivative having the required Tc (38-39 °C) for the given aqueous medium required in cell experiments through careful selection of the degree of substitution. This thermosensitive derivative can encapsulate doxorubicin (DOX), a well-known anticancer agent, and was further studied as a temperature-triggered drug delivery system. Although the polymeric carrier showed no notable toxicity at temperatures either below or above the transition temperature, the thermoresponsive drug-loaded formulation exhibited increased DOX cellular uptake and improved in vitro cytotoxicity at 40 °C.

Maternal serum placental growth factor, pregnancy-associated plasma protein-a and free ß-human chorionic gonadotrophin at 30-33 weeks in the prediction of pre-eclampsia.

OBJECTIVE: To investigate the potential value of maternal serum concentrations of free ß-human chorionic gonadotrophin (ß-hCG), pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) at 30-33 weeks of gestation in the prediction of pre-eclampsia (PE) developing at or after 34 weeks. METHODS: Serum free ß-hCG, PAPP-A and PlGF were measured at 11-13 and at 30-33 weeks of gestation in a case-control study of 50 cases that developed PE at or after 34 weeks and 250 unaffected controls. The measured concentration of metabolites was converted into multiples of the unaffected median (MoM) and the MoM values in the PE and control groups were compared. RESULTS: At 11-13 weeks, serum PlGF and PAPP-A, but not free ß-hCG, were significantly lower in the PE group than in the controls (0.824, 0.748 and 0.857 vs. 1.000 MoM). At 30-33 weeks in the PE group, PlGF was reduced (0.356 MoM), free ß-hCG was increased (1.750 MoM), but PAPP-A was not significantly different (0.991 MoM) from control (1.000 MoM). In screening for PE at 30-33 weeks by a combination of maternal characteristics and serum PlGF, the estimated detection rates, at a false-positive rate of 10%, of intermediate PE (requiring delivery at 34-37 weeks) and late PE (with delivery after 37 weeks) were 85.7 and 52.8%, respectively. The performance of screening was not improved by the addition of free ß-hCG or the free ß-hCG/PlGF ratio. CONCLUSION: Screening by maternal characteristics and serum PlGF at 30-33 weeks could identify most pregnancies that will subsequently develop PE.

Second-trimester screening for trisomy-21 using prefrontal space ratio.

OBJECTIVE: To investigate the potential value of prefrontal space ratio (PFSR) in second-trimester screening for trisomy-21. METHODS: A retrospective study utilizing stored midsagittal two-dimensional images of fetal profiles in 240 euploid and 45 trisomy-21 pregnancies at 16(+0)-23(+6) weeks' gestation. The vertical distance between the leading edge of the skull and that of the skin (D1) and the distance between the skull and the mandibulo-maxillary line (D2) were measured and the D1:D2 ratio (PFSR) was calculated. In euploid pregnancies, regression analysis was used to determine the association between D1, D2 and PFSR with gestational age (GA). D1 and D2 were expressed as delta (Δ) values with gestational age. ΔD1, ΔD2 and PFSR in cases and controls were compared. RESULTS: In trisomy-21, compared to controls, ΔD1 was increased (1.417 vs. 0.000 mm, p < 0.0001), ΔD2 was decreased (-0.842 vs. 0.000 mm, p = 0.003) and PFSR was increased (0.753 vs. 0.463, p < 0.0001). At a false-positive rate of 5%, the detection rates in screening by ΔD1, ΔD2 and PSFR were 80.0% (95% CI 65.4-90.4), 46.7% (95% CI 31.7-62.1) and 100.0% (95% CI 92.1-100.0), respectively. CONCLUSION: The PFSR is an effective marker in second-trimester screening for trisomy-21.