Preparation of liposomes encapsulating water-soluble compounds using supercritical carbon dioxide.

In this paper the development of a new preparation method of liposomes containing a water soluble marker (fluorescein isothiocyanate-dextran (FITC-dextran) or zinc phthalocyanine tetrasulfonic acid (TSZnPc) using supercritical carbon dioxide (called "the supercritical liposome method") is described. The apparatus used consisted of two main parts: the high-pressure part, in which the lipid components 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and cholesterol (Chol) (7:3 molar ratio) were dissolved under pressure in supercritical carbon dioxide, and a low-pressure part, in which the homogeneous supercritical solution is expanded and simultaneously mixed with the aqueous phase to yield liposomes encapsulating the water soluble marker. Addition of 7% absolute ethanol to carbon dioxide at 25 MPa and 60 degrees C and the use of a high-pressure recycling system during 30 min form the homogeneous solution with high reproducibility of both lipid components and resulted in an equal expansion profile (recovery after expansion versus time) of POPC and Chol. Incubation of the lipid components during 60 min at the above mentioned conditions generated only 3% degradation. The average size of the liposomes was about 200 nm and could not be influenced by the experimental conditions used. Optimal values for encapsulated volume (1.25 L/mol) and efficiency (20%) of the liposomes were obtained using statistical experimental design by using the water soluble marker TSZnPc and an encapsulation capillary with 5.0 cm length and 0.5 mm inner diameter. The total amount of ethanol used to obtain an encapsulation efficiency of 20% was 15-fold reduced compared to the ethanol injection method of Batzri and Korn (Biochim. Biophys. Acta 1973, 298, 1015-1019).

Simulated descent v dexamethasone in treatment of acute mountain sickness: a randomised trial.

OBJECTIVE: Evaluation and comparison of the therapeutic efficacy of a portable hyperbaric chamber and dexamethasone in the treatment of acute mountain sickness. DESIGN: Randomised trial during the summer mountaineering season. SETTING: High altitude research laboratory in the Capanna Regina Margherita at 4559m above sea level (Alps Valais). SUBJECTS: 31 climbers with symptoms of acute mountain sickness randomly assigned to different treatments. INTERVENTIONS: One hour of treatment in the hyperbaric chamber at a pressure of 193 mbar or oral administration of 8 mg dexamethasone initially, followed by 4 mg after 6 hours. MAIN OUTCOME MEASURES: Symptoms of acute mountain sickness (Lake Louise score, clinical score, and AMS-C score) before one and about 11 hours after beginning the different methods of treatment. Permitted intake of mild analgesics before treatment and in the follow up period. RESULTS: After one hour of treatment compression with 193 mbar caused a significantly greater relief of symptoms of acute mountain sickness than dexamethasone (Lake Louise score: mean (SD) -4.6 (1.9) v -2.5 (1.8); clinical score: -4.0 (1.2) v -1.5 (1.4); AMS-C score: -1.24 (0.51) v -0.54 (0.59)). In contrast after about 11 hours subjects treated with dexamethasone suffered from significantly less severe acute mountain sickness than subjects treated with the hyperbaric chamber (-7.0 (3.6) v -1.6 (3.0); -4.1 (1.9) v -1.0 (1.5); -1.78 (0.73) v -0.75 (0.82) respectively). Intake of analgesics was similar in both groups. CONCLUSION: Both methods were efficient in treatment of acute mountain sickness. One hour of compression with 193 mbar in the hyperbaric chamber, corresponding to a descent of 2250 m, led to short term improvement but had no long term beneficial effect. On the other hand, treatment with dexamethasone in an oral dose of 8 mg initially followed by 4 mg every 6 hours resulted in a longer term clinical improvement. For optimal efficacy the two methods should be combined if descent or evacuation is not possible.

Allelic loss on a chromosome 17 in ductal carcinoma in situ of the breast.

Multiple tumor suppressor genes are implicated in the oncogenesis and progression of invasive carcinoma of the breast. To investigate the chronology of genetic changes we studied loss of heterozygosity on chromosome 17 in ductal carcinoma in situ, a preinvasive breast cancer. A microdissection technique was used to separate tumor from normal stromal cells prior to DNA extraction and loss of heterozygosity was assayed mainly using simple sequence repeat polymorphism markers and the polymerase chain reaction. Loss of heterozygosity on 17p was observed in 8 of 28 tumors (29%) when compared with normal control DNA, whereas no loss was seen on 17q, suggesting that at least one locus on 17p is involved early in the development of breast cancer.

Social decentering and locus of control in children.

Relationships beteen social decentering, personality variables, and social competence were investigated for children attending a seven-week therapeutic summer camp. Ss were 23 males and females ranging in age from 10 to 13 years old had been referred to the camp because they lacked age-appropriate social skills. Feffer's Role Taking Task was used to measure social decentering, and counselor ratings of camper adjustment were measures of social competence. Predicted positive relationships between decentering and competence were found. Striking sex differences were found, however, when comparisons were made between social decentering and two personality variables--the Nowicki-Strickland Locus of Control Scale and the Kiddie Mach. Predicted negative correlations were found between Role Taking Task scores and externality and machiavellianism for females, but not for males. Implications concerning age by sex interactions in the study of personality correlates of social decentering were discussed.