In situ biosurfactant production by Bacillus strains injected into a limestone petroleum reservoir.

Biosurfactant-mediated oil recovery may be an economic approach for recovery of significant amounts of oil entrapped in reservoirs, but evidence that biosurfactants can be produced in situ at concentrations needed to mobilize oil is lacking. We tested whether two Bacillus strains that produce lipopeptide biosurfactants can metabolize and produce their biosurfactants in an oil reservoir. Five wells that produce from the same Viola limestone formation were used. Two wells received an inoculum (a mixture of Bacillus strain RS-1 and Bacillus subtilis subsp. spizizenii NRRL B-23049) and nutrients (glucose, sodium nitrate, and trace metals), two wells received just nutrients, and one well received only formation water. Results showed in situ metabolism and biosurfactant production. The average concentration of lipopeptide biosurfactant in the produced fluids of the inoculated wells was about 90 mg/liter. This concentration is approximately nine times the minimum concentration required to mobilize entrapped oil from sandstone cores. Carbon dioxide, acetate, lactate, ethanol, and 2,3-butanediol were detected in the produced fluids of the inoculated wells. Only CO(2) and ethanol were detected in the produced fluids of the nutrient-only-treated wells. Microbiological and molecular data showed that the microorganisms injected into the formation were retrieved in the produced fluids of the inoculated wells. We provide essential data for modeling microbial oil recovery processes in situ, including growth rates (0.06 +/- 0.01 h(-1)), carbon balances (107% +/- 34%), biosurfactant production rates (0.02 +/- 0.001 h(-1)), and biosurfactant yields (0.015 +/- 0.001 mol biosurfactant/mol glucose). The data demonstrate the technical feasibility of microbial processes for oil recovery.

In vitro evaluation of a series of N-dodecanoyl-L-amino acid methyl esters as dermal penetration enhancers.

A series of N-dodecanoyl-L-amino acid methyl esters (1-10) and n-pentyl N-acetylprolinate (11) were evaluated for dermal enhancement properties using an in vitro diffusion cell technique. Methods of synthesis of these compounds were described. Enhancers were applied 1 h prior to drug treatment. Hydrocortisone was used as the model drug and was applied to excised hairless mouse skin as a saturated suspension in propylene glycol. Enhancement ratios (ER) were determined for permeability coefficient, 24 h diffusion cell receptor concentration (Q24), and 24 h full-thickness skin steroid content. Controls received no enhancer pretreatment of the skin. N-Dodecanoyl-L-proline (10) showed the highest Q24 value for total steroid (ER 13.7) while N-dodecanoyl-L-phenylalanine (5) showed the highest total steroid skin retention (ER 16.5).

Altered disposition and antidepressant activity of imipramine in transgenic mice with elevated alpha-1-acid glycoprotein.

Imipramine is a tricyclic antidepressant known to be bound in the serum primarily by alpha-1-acid glycoprotein. The present study examined the effect of changes in serum alpha-1-acid glycoprotein levels on the pharmacokinetics and antidepressant activity of the drug by utilizing a novel set of transgenic mice in which the steady-state level of alpha-1-acid glycoprotein is significantly elevated over normal. The pharmacokinetic disposition was characterized after i.v. and i.p. injections in transgenic and control mice. In transgenic mice, there were significant decreases in the serum unbound fraction (0.62+/- 0.38 vs.2.48 +/- 0.43%), Vd (9.0 +/- 2.5 vs. 22.4 +/- 3.2 liters/kg), T1/2 (35.0 +/- 7.6 vs. 65.3 +/- 7.6 min) and fraction of dose excreted unchanged in urine (0.14 +/- 0.07 vs. 0.70 +/- 0.20%) with no significant alterations in systemic clearance (204.7 +/- 56.1 vs. 292.8 +/- 58.4 ml/min/kg) compared to control values. The antidepressant activity of imipramine was measured by a swimming-immobility test 30 min after either imipramine (30 mg/kg i.p.) or saline treatment. After saline treatment, there were no significant differences in the duration of swimming despair between transgenic (183 +/- 24 sec) and control (175 +/- 12 sec) mice. Imipramine treatment resulted in reductions in the duration of immobility in both transgenic (130 +/- 21 sec) and control (54 +/- 33 sec) mice. The extent of reduction was significantly less in transgenic animals than in control animals. These alterations in the antidepressant action appeared to correlate with the unbound drug concentration but not with the total drug concentration.

Rapid microsample analysis of imipramine and desipramine by reversed-phase high-performance liquid chromatography with ultraviolet detection.

A rapid and highly sensitive HPLC assay method was developed to measure small amounts of imipramine and its major metabolite, desipramine. The assay involved simple extraction procedures using clomipramine as the internal standard. The mobile phase consisted of acetonitrile (60%) and 0.01 M triethylamine in distilled water (40%) with the pH adjusted to 3.0. Separations were achieved on a C18 column and the effluent measured for UV absorption at 260 nm. The chromatographic separation was excellent, with no interference from endogenous serum constituents. This assay was suitable for measuring drug concentrations in the range of 10-1000 ng/ml using a 0.1-ml serum sample. The method was applied to a drug disposition study in transgenic mice with increased plasma alpha 1-acid glycoprotein.

Mammary excretion of cannabidiol in rabbits after intravenous administration.

The present study examined the distribution of cannabidiol into milk after an intravenous bolus injection (3 mg kg-1) to lactating rabbits. Drug concentrations in milk and serum were measured by HPLC. Cannabidiol was excreted into milk rapidly and the drug levels in milk increased over a 4-24-h period following the maternal injection. The mean milk to serum concentration ratio was 25.9, indicating a significant accumulation of the drug in milk.