Transport of GM1 and GM1 inner ester across an in vitro model of the blood-brain barrier

Gangliosides, especially GM1, attenuate the in vivo damage caused by various neurotoxins. The chemically neutral inner ester of GM1 may be a better cytoprotective agent against some neurotoxins than the parent GM1 compound, because it may cross the blood-brain barrier (BBB) more easily than the anionic GM1. Using an in vitro bovine brain endothelial cell model of the BBB, we show the inner ester more readily transverse the tight junction barrier of this model than does GM1. Further, it is demonstrated that the GM1 inner ester is stable for several hours at pH values between 7.0 and 8.2 at 37 degrees C. Finally, the results illustrate that the BBB model may be useful for testing other gangliosides and their various derivatives for increased ability to cross the BBB.     

Determination of cyclic fatty acids by gas-liquid chromatography

A method is described to determine cyclic fatty acids in cyclic monomers by gas-liquid chromatography (GLC), which separates saturated straight-chain esters from cyclic esters. The content of cyclic esters can be determined by integration of the area on the chromatograph under the cyclic peaks. GLC was applied to cyclic monomers made from linseed oil and from linolenic acid. Samples of both hydrogenated and nonhydrogenated cyclic monomers were analyzed; however, more reliable results were obtained on the hydrogenated samples. The results show a standard deviation of 0.25 for linseed oil and 0.36 for linolenic acid. Accuracy of the analysis was established by comparing data with that obtained by crystallization. The GLC method is approximately three times faster. Presented at the AOCS meeting, New Orleans, La., 1962. A laboratory of the No. Utiliz. Res. & Dev. Div., ARS, U.S.D.A.     

Production of cyclic fatty acids: Water as the reaction solvent

In an attempt to lower processing costs of producing cyclic fatty acids by a high-temperature alkali treatment, water was tested as the reaction solvent instead of ethylene glycol, previously used. Based on extensive tests in a high-pressure autoclave, saturated cyclic (cyclohexanoic) fatty acids were produced under economic reaction conditions, including a temperature of about 300C; a 4:1 solvent ratio and 50% excess sodium hydroxide catalyst. The lower yield of saturated cyclic fatty acids by the water process is more than offset by the fewer steps and reduced evaporation costs. Presented at the AOCS Meeting, Chicago, Ill., 1964. A laboratory of the No. Utiliz. Res. & Dev. Div., ARS, USDA.     

Phase I and pharmacologic study of 9-aminocamptothecin colloidal dispersion formulation given as a 24-hour continuous infusion weekly times four every 5 weeks

PURPOSE: 9-Aminocamptothecin (9-AC) is a water-insoluble camptothecin (CMP) derivative that inhibits normal topoisomerase I function. Schedule dependency was noted, with the greatest activity seen in the setting of greater than 24 hours exposure to lactone (L) concentrations > or = 10 nmol/L. In this phase I study, 9-AC was given by a continuous intravenous infusion over 24 hours once weekly times four every 5 weeks. PATIENTS AND METHODS: Twenty patients, of whom 16 had fluorouracil-refractory colorectal cancer (CRC), entered the study. Dose levels were 0.7 mg/m2 (n = 4), 1.4 mg/m2 (n = 3), 1.9 mg/m2 (n = 6), and 1.65 mg/m2 (n = 7). Detailed pharmacokinetic (PK) measurements of 9-AC L and carboxylate (C) were performed on day 1 of cycles 1 and 2. RESULTS: At 1.9 mg/m2, dose-limiting toxicity (DLT) was reached, with three of six patients having grade 4 neutropenia. At 1.65 mg/m2, one of seven patients had grade 4 neutropenia. Nonhematologic toxicity was modest, with diarrhea > or = grade 3 in two patients and lethargy > or = grade 3 in eight. PK/pharmacodynamic (PD) analyses showed marked interpatient variability. Steady-state concentrations (Css) of 9-AC L > or = 10 nmol/L (3.6 microg/L) were seen in five of seven patients at 1.65 mg/m2 and five of six patients at 1.9 mg/m2. Using the sigmoidal maximal effect (Emax) model, 9-AC L area under the concentration-time curve (AUC) and Css correlated with day 15 decrease in neutrophils (R2 = .47), but not platelets. CONCLUSION: The recommended phase II dose of 9-AC colloidal dispersion (CD) given as a 24-hour continuous infusion weekly for 4 of every 5 weeks is 1.65 mg/m2.     

Technische und wirtschaftliche Gesichtspunkte bei der Bereitstellung der forstlichen Biomasse

The arrcars in thinning, the growing demand, for raw wood by the wood working industry and the increase in raw material prices on the international markets are the reasons why work science will have to develop new methods of yield which allow wood mass above the ground to be utilized to a greater degree. In this paper, several methods of processing and the machines applied presently in Central Europe and Scandinavia are described. The suitability of these methods and machines, their efficiency and various economic aspects are dealt with and evaluated in summary.     

Successful re-treatment with taxol after major hypersensitivity reactions

PURPOSE: To describe the successful re-treatment of eight patients who had major hypersensitivity reactions (HSRs) to taxol and to suggest a regimen for re-treating patients who develop major HSRs. PATIENTS AND METHODS: The treatment courses of eight patients who developed major HSRs and were rechallenged with taxol were reviewed. Patients in this report represent all patients who are known to have been rechallenged with taxol after major HSRs. RESULTS: The most common approach used to rechallenge patients consisted of premedication with multiple high doses of corticosteroids and H1- and H2-histamine antagonists followed by the initiation of the taxol infusion at a reduced rate. All patients who experienced major HSRs were rechallenged successfully. After the rechallenge, these patients received 32 additional courses of taxol without HSRs. CONCLUSION: Re-treatment with taxol after major HSRs is feasible using multiple high doses of corticosteroids and antihistamine premedications and a reduced taxol infusion rate under close supervision. This approach may represent a valid alternative to the termination of taxol; however, a prospective evaluation is required to determine the true efficacy of this approach.