Local Transdermal Delivery of Telapristone Acetate Through Breast Skin, Compared With Oral Treatment: A Randomized Double-Blind, Placebo-Controlled Phase II Trial

Oral breast cancer prevention medications entail systemic exposure, limiting acceptance by high-risk women. Delivery through the breast skin, although an attractive alternative, requires demonstration of drug distribution throughout the breast. We conducted a randomized double-blind, placebo-controlled phase II clinical trial comparing telapristone acetate, a progesterone receptor antagonist, administered orally (12 mg/day) or transdermally (12 mg/breast) for 4 ± 1 weeks to women planning mastectomy. Plasma and tissue concentrations, measured at five locations in the mastectomy specimen using liquid chromatography tandem mass spectrometry were compared. In 60 evaluable subjects, median drug concentration (ng/g tissue) was 103 (interquartile range (IQR): 46.3–336) in the oral vs. 2.82 (IQR: 1.4–5.5) in the transdermal group. Despite poor dermal permeation, within-breast drug distribution pattern was identical in both groups (R2 = 0.88, P = 0.006), demonstrating that transdermally and orally delivered drug is distributed similarly through the breast, and is strongly influenced by tissue adiposity (P < 0.0001). Other skin-penetrant drugs should be tested for breast cancer prevention

Membrane chemical stability and seed longevity

Here, we investigate the relationships between the chemical stability of the membrane surface and seed longevity. Dry embryos of long-lived tomato and short-lived onion seeds were labeled with 5-doxyl-stearic acid (5-DS). Temperature-induced loss of the electron spin resonance signal caused by chemical conversion of 5-DS to nonparamagnetic species was used to characterize the membrane surface chemical stability. No difference was found between temperature plots of 5-DS signal intensity in dry onion and tomato below 345 K. Above this temperature, the 5-DS signal remained unchanged in tomato embryos and irreversibly disappeared in onion seeds. The role of the physical state and chemical status of the membrane environment in the chemical stability of membrane surfaces was estimated for model systems containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) dried alone or in the presence of trehalose or glucose. Fourier transform infrared spectroscopy was used to follow temperature-induced structural changes in dry POPC. Spin-label technique was used to relate the chemical stability of 5-DS with the dynamic properties of the bilayer and 5-DS motion behavior. In all the models, the decrease in 5-DS signal intensity was always observed above Tm for the membrane surface. The 5-DS signal was irreversibly lost at high temperature when dry POPC was embedded in a glucose matrix. The loss of 5-DS signal was moderate when POPC was dried alone or in the presence of trehalose. Comparison of model and in vivo data shows that the differences in longevity between onion and tomato seeds are caused by differences in the chemical status of the membrane surface rather than the degree of its immobilization

Yeasts and bacterial biosurfactants as demulsifiers for petroleum derivative in seawater emulsions

Abstract Oil sludge or waste generated in transport, storage or refining forms highly stable mixtures due to the presence and additives with surfactant properties and water forming complex emulsions. Thus, demulsification is necessary to separate this residual oil from the aqueous phase for oil processing and water treatment/disposal. Most used chemical demulsifiers, although effective, are environmental contaminants and do not meet the desired levels of biodegradation. We investigated the application of microbial biosurfactants as potential natural demulsifiers of petroleum derivatives in water emulsions. Biosurfactants crude extracts, produced by yeasts (Candida guilliermondii, Candida lipolytica and Candida sphaerica) and bacteria (Pseudomonas aeruginosa, Pseudomonas cepacia and Bacillus sp.) grown in industrial residues, were tested for demulsification capacity in their crude and pure forms. The best results obtained were for bacterial biosurfactants, which were able to recover about 65% of the seawater emulsified with motor oil compared to 35–40% only for yeasts products. Biosurfactants were also tested with oil-in-water (O/W) and water-in-oil (W/O) kerosene model emulsions. No relationship between interfacial tension, cell hydrophobicity and demulsification ratios was observed with all the biosurfactants tested. Microscopic illustrations of the emulsions in the presence of the biosurfactants showed the aspects of the emulsion and demulsification process. The results obtained demonstrate the potential of these agents as demulsifiers in marine environments

Role of standard chemical potential in transport through anisotropic media and asymmetrical membranes

Journal of Physical Chemistry B107317830-7837JPCB

Choice and Interpretation of Statistical Tests Used When Competing Risks Are Present

In clinical cancer research, competing risks are frequently encountered. For example, individuals undergoing treatment for surgically resectable disease may experience recurrence near the removed tumor, metastatic recurrence at other sites, occurrence of second primary cancer, or death resulting from noncancer causes before any of these events. Two quantities, the cause-specific hazard function and the cumulative incidence function, are commonly used to summarize outcomes by event type. Tests for event-specific differences between treatment groups may thus be based on comparison of (a) cause-specific hazards via a log-rank or related test, or (b) the cumulative incidence functions via one of several available tests. Inferential results for tests based on these different metrics can differ considerably for the same cause-specific end point. Depending on the questions of principal interest, one or both metrics may be appropriate to consider. We present simulation study results and discuss examples from cancer clinical trials to illustrate these points and provide guidance for analysis when competing risks are present

Copper corrosion in mildly alkaline water with the disinfectant monochloramine

10.1016/S0010-938X(02)00021-5Corrosion Science44112507-2528CRRS

DSC and EPR investigations on effects of cholesterol component on molecular interactions between paclitaxel and phospholipid within lipid bilayer membrane

10.1016/j.ijpharm.2007.01.045International Journal of Pharmaceutics3381-2258-266IJPH