Drug delivery to the brain is hindered by the presence of the blood-brain barrier (BBB). Although the BBB restricts the passage of many substances, it is actually selectively permeable to nutrients necessary for healthy brain function. To accomplish the task of nutrient transport, the brain endothelium is endowed with a diverse collection of molecular transport systems. One such class of transport system, known as a receptor-mediated transcytosis (RMT), employs the vesicular trafficking machinery of the endothelium to transport substrates between blood and brain. If appropriately targeted, RMT systems can also be used to shuttle a wide range of therapeutics into the brain in a noninvasive manner. Over the last decade, there have been significant developments in the arena of RMT-based brain drug transport, and this review will focus on those approaches that have been validated in an in vivo setting.

In vitro blood-brain barrier (BBB) models using primary rat brain microvessel endothelial cells (BMEC) are often hampered by a lack of culture purity and poor barrier properties. To address these problems, the translation inhibitor puromycin was used to purify rat BMEC cultures. BMEC purities of 99.8% were routinely attained using puromycin treatment, and this technique proved to be far superior to other purification methods of similar difficulty. In contrast to cultures without puromycin treatment, purity of puromycin-treated cultures was unaffected by initial seeding density. Next, rat BMEC monolayer transendothelial electrical resistance (TEER) was increased by glucocorticoid treatment with either corticosterone (CORT) or hydrocortisone (HC), and a corresponding decrease in monolayer permeability to small molecules was observed. Importantly, cultures treated with both puromycin and glucocorticoid attained significantly higher TEER values (CORT 168 ± 13 W · cm 2 ; HC 218 ± 66 W · cm 2 ) than those treated by the glucocorticoid alone (CORT 57 ± 5 W · cm 2 ;HC 70 ± 2 W · cm 2 ). Glucocorticoid induction resulted in BMEC morphological changes that accompanied the increases in TEER, and BMEC tight junctions exhibited improved integrity as visualized by the localization of tight junction proteins zonula occluden-1, occludin and claudin-5. The combined use of puromycin and glucocorticoid therefore provides an in vitro system that is well suited for molecular level BBB investigations. The cerebral microvasculature separates the brain interior from the bloodstream and has been termed the blood-brain barrier (BBB) as a result of its impermeable properties. The BBB assists in maintaining brain homeostasis and protects the brain against harmful blood-borne substances. A single layer of brain microvascular endothelial cells (BMEC) is responsible for the limited solute transfer between blood and brain, and these specialized endothelial cells (EC) display distinctive attributes when compared with peripheral endothelium. Low BMEC permeability results from continuous tight junctions between adjoining ECs (Reese and Karnovsky 1967), low levels of pinocytosis and a general lack of fenestrae (Brightman and Reese 1969;Joo 1971). Because of the impermeable phenotype, the BBB plays major roles in disease pathology and hinders drug delivery efforts. Because of the inherent difficulties in performing molecular level studies of disease pathology in vivo, and the fact that prediction of BBB drug permeability prior to animal studies would be highly advantageous, a representative in vitro model would be of high utility. Unfortunately, when

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Plant roots secrete a complex polysaccharide mucilage that may provide a significant source of carbon for microbes that colonize the rhizosphere. High molecular weight mucilage was separated by high-pressure liquid chromatography gel filtration from low molecular weight components of pea root exudate. Purified pea root mucilage generally was similar in sugar and glycosidic linkage composition to mucilage from cowpea, wheat, rice, and maize, but appeared to contain an unusually high amount of material that was similar to arabinogalactan protein. Purified pea mucilage was used as the sole carbon source for growth of several pea rhizosphere bacteria, including Rhizobium leguminosarum 8401 and 4292, Burkholderia cepacia AMMD, and Pseudomonas fluorescens PRA25. These species grew on mucilage to cell densities of three- to 25-fold higher than controls with no added carbon source, with cell densities of 1 to 15% of those obtained on an equal weight of glucose. Micromolar concentrations of nod gene-inducing flavonoids specifically stimulated mucilage-dependent growth of R. leguminosarum 8401 to levels almost equaling the glucose controls. R. leguminosarum 8401 was able to hydrolyze p-nitrophenyl glycosides of various sugars and partially utilize a number of purified plant polysaccharides as sole carbon sources, indicating that R. leguminosarum 8401 can make an unexpected variety of carbohydrases, in accordance with its ability to extensively utilize pea root mucilage.

Rising numbers of women arrested for domestic violence present many theoretical and practical challenges. At the theoretical level, there is ongoing debate about whether women are equally aggressive as men. At the practical level, little research is available to guide how female cases are handled in the criminal justice system. In this study, data were obtained regarding demographic characteristics, mental health functioning, and childhood familial dysfunction for a large sample of male (n = 2,254) and female (n = 281) domestic violence offenders. The women were demographically similar to the men, and few differences were noted in their childhood experiences. Women were more likely than men to have previously attempted suicide, whereas more men had conduct problems in childhood and substance abuse in adulthood. Compared to the male offenders, women reported more symptoms of personality dysfunction and mood disorder. Treatment implications of these findings are discussed.