Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states.

Berberine has been shown to have antidiabetic properties, although its mode of action is not known. Here, we have investigated the metabolic effects of berberine in two animal models of insulin resistance and in insulin-responsive cell lines. Berberine reduced body weight and caused a significant improvement in glucose tolerance without altering food intake in db/db mice. Similarly, berberine reduced body weight and plasma triglycerides and improved insulin action in high-fat-fed Wistar rats. Berberine downregulated the expression of genes involved in lipogenesis and upregulated those involved in energy expenditure in adipose tissue and muscle. Berberine treatment resulted in increased AMP-activated protein kinase (AMPK) activity in 3T3-L1 adipocytes and L6 myotubes, increased GLUT4 translocation in L6 cells in a phosphatidylinositol 3' kinase-independent manner, and reduced lipid accumulation in 3T3-L1 adipocytes. These findings suggest that berberine displays beneficial effects in the treatment of diabetes and obesity at least in part via stimulation of AMPK activity.

Methods for predicting migration to packaged pharmaceuticals.

The compatibility of the pharmaceutical product with packaging materials is an important parameter which must be evaluated during the product development process. This paper discusses the possibility that pertinent FDA methodology can be modified in a more efficient way using currently available analytical techniques. Several studies on potential migrants from packaging materials, such as heat-seal adhesives, amber polyethylene terephthalate (PET) containers, and rubber gaskets of aerosol valves, are presented to show that commonly encountered questions with regard to packaging materials used during product stability studies can also be answered in the same way.

Determination of emamectin residues in the tissues of Atlantic salmon (Salmo salar L.) using HPLC with fluorescence detection.

An accurate, reliable, and reproducible assay for the determination of residual concentrations of emamectin B(1a) in muscle, skin, and intact muscle/skin in natural proportions from Atlantic salmon treated with SCH 58854 (emamectin benzoate) is described. The determinative method was developed and validated using fortified control tissues at five levels over a range of 50-800 ng/g as well as tissues containing incurred levels in the same range. Incurred tissues were obtained from a metabolism study of [(3)H]emamectin benzoate in Atlantic salmon. The assay employs processing of a tissue ethyl acetate extract on a propylsulfonic acid solid phase extraction cartridge, followed by derivatization with trifluoroacetic anhydride in the presence of N-methylimidazole. Following separation using reversed phase HPLC, the amount of derivatized emamectin B(1a) is determined by fluorescence detection. The theoretical limits of detection were determined from the analysis of control tissue matrices to be 2.6, 3.3, and 3.8 ng/g as emamectin B(1a) for muscle, skin, and intact muscle/skin, respectively. Likewise, the theoretical limits of quantitation (LOQ) were determined to be 6.9, 8.1, and 9.5 ng/g as emamectin B(1a) for muscle, skin, and intact muscle/skin, respectively. The lowest fortification level used for method validation was 50 ng/g, which served as the effective LOQ for the method. The overall percent recoveries (+/-% CV) were 94.4 +/- 6.89% (n = 25) for muscle, 88.4 +/- 5.35% (n = 25) for skin, and 88.0 +/- 3.73% for intact muscle/skin (n = 25). Accuracy, precision, linearity, selectivity, and ruggedness were demonstrated. The structure of the final fluorescent derivative of emamectin B(1a) free base was identified by ESI(+)/LC-MS. The frozen storage stability of [(3)H]emamectin B(1a) in tissues with incurred residues was demonstrated for approximately 15 months by radiometric analysis and for an additional approximately 13 months by fluorometric analysis for a total of approximately 28 months.

Volatiles in packaging materials.

The increasing application of complex natural and/or synthetic polymers to food packaging has required definitive information on the characteristics of the finished products. High temperature encountered during the manufacturing process may induce thermal decomposition products that can migrate into the packaged product and cause undesirable flavor. A general methodology for testing polymer odor and odor contributors is discussed in this article with examples representing the odor of a variety of packaging materials. The precursors and the mechanisms of the major volatile components of each packaging material are presented.

Fate of

The nature and magnitude of residues in apples treated with [(14)C]diphenylamine (DPA) was investigated following treatment and storage at reduced temperature. Additional apples were treated with a mixture of [(14)C]DPA and deuterium-labeled DPA (D-10-DPA) for use in metabolite identification. Stored apples were sampled at 16 different intervals throughout a 40-week period. Total radioactive residue levels remained constant over the entire testing interval. The parent chemical and several metabolites were identified on the final harvest peel and pulp samples by quantitative and qualitative analytical methods. A majority of the terminal residue, which was confined largely in the peel, consisted of unmetabolized DPA. Residues in pulp, however, were largely composed of glycosyl conjugates of several hydroxylated diphenylamine (OH-DPA) metabolites. The major polar metabolite identified in stored apples was a glucose conjugate of 4-hydroxydiphenylamine (4-OH-DPA). Additional metabolites, characterized as glycosyl conjugates of 2-OH-DPA, 3-OH-DPA, 4-OH-DPA, or dihydroxy-DPA, were also detected along with their intact (i.e., nonconjugated) forms in apple pulp.