Literature Review: Investigating Drug Transport at the Blood-Brain Barrier and the Effects of P-glycoprotein on the Brain Distribution of Drugs.

The blood-brain barrier (BBB) is a unique barrier that strictly regulates the entry of endogenous substrates and xenobiotics into the brain. This is due to its tight junctions and the array of transporters and metabolic enzymes that are expressed. The determination of brain concentrations in vivo is difficult, laborious and expensive which means that there is interest in developing predictive tools of brain distribution. Predicting brain concentrations is important even in early drug development to ensure efficacy of central nervous system (CNS) targeted drugs and safety of non-CNS drugs. The literature review covers the most common current in vitro, in vivo and in silico methods of studying transport into the brain, concentrating on transporter effects. The consequences of efflux mediated by p-glycoprotein, the most widely characterized transporter expressed at the BBB, is also discussed. The aim of the experimental study was to build a pharmacokinetic (PK) model to describe p-glycoprotein substrate drug concentrations in the brain using commonly measured in vivo parameters of brain distribution. The possibility of replacing in vivo parameter values with their in vitro counterparts was also studied. All data for the study was taken from the literature. A simple 2-compartment PK model was built using the Stella™ software. Brain concentrations of morphine, loperamide and quinidine were simulated and compared with published studies. Correlation of in vitro measured efflux ratio (ER) from different studies was evaluated in addition to studying correlation between in vitro and in vivo measured ER. A Stella™ model was also constructed to simulate an in vitro transcellular monolayer experiment, to study the sensitivity of measured ER to changes in passive permeability and Michaelis-Menten kinetic parameter values. Interspecies differences in rats and mice were investigated with regards to brain permeability and drug binding in brain tissue. Although the PK brain model was able to capture the concentration-time profiles for all 3 compounds in both brain and plasma and performed fairly well for morphine, for quinidine it underestimated and for loperamide it overestimated brain concentrations. Because the ratio of concentrations in brain and blood is dependent on the ER, it is suggested that the variable values cited for this parameter and its inaccuracy could be one explanation for the failure of predictions. Validation of the model with more compounds is needed to draw further conclusions. In vitro ER showed variable correlation between studies, indicating variability due to experimental factors such as test concentration, but overall differences were small. Good correlation between in vitro and in vivo ER at low concentrations supports the possibility of using of in vitro ER in the PK model. The in vitro simulation illustrated that in the simulation setting, efflux is significant only with low passive permeability, which highlights the fact that the cell model used to measure ER must have low enough paracellular permeability to correctly mimic the in vivo situation.

Mutation analysis of the SLC4A11 gene in Indian families with congenital hereditary endothelial dystrophy 2 and a review of the literature

Purpose: Congenital hereditary endothelial dystrophy 2 (CHED2) is an autosomal recessive disorder caused by mutations in the solute carrier family 4, sodium borate transporter, member 11 (SLC4A11) gene. The purpose of this study was to identify the genetic cause of CHED2 in six Indian families and catalog all known mutations in the SLC4A11 gene. Methods: Peripheral blood samples were collected from individuals of the families with CHED2 and used in genomic DNA isolation. PCR primers were used to amplify the entire coding region including intron-exon junctions of SLC4A11. Amplicons were subsequently sequenced to identify the mutations. Results: DNA sequence analysis of the six families identified four novel (viz., p.Thr262Ile, p.Gly417Arg, p.Cys611Arg, and p.His724Asp) mutations and one known p.Arg869His homozygous mutation in the SLC4A11 gene. The mutation p.Gly417Arg was identified in two families. Conclusions: This study increases the mutation spectrum of the SLC4A11 gene. A review of the literature showed that the total number of mutations in the SLC4A11 gene described to date is 78. Most of the mutations are missense, followed by insertions-deletions. The present study will be helpful in genetic diagnosis of the families reported here.

Revenue management in remanufacturing: perspectives, review of current literature and research directions

The pace of development in the world has increased over the years and with it, the use of hi-tech gadgets, consumer durables, automobiles, etc. has also gone up. In this context, as resources become more and more scarce, there are multiple challenges that emerge both from a sustainable development perspective, and from the perspective of meeting profitability objectives of a firm. Remanufacturing has come up in a big way as an answer to these challenges, but firms are struggling with respect to revenue management of this nascent area. We assess the current literature and distil the key factors that firms need to consider as they assimilate remanufacturing in their operations and revenue management strategy. We provide an assessment of white spaces in research in this area and also outline the directions for future research.

Review of World literature on Water Chestnut with implications for management in North America

Water chestnut (Trapa natans L.,sensu lato) is an annual, floating-leaved aquatic plant of temperate and tropical freshwater wetlands, rivers, lakes, ponds, and estuaries. Native to Eurasia and Africa, water chestnut has been widely gathered for its large nutritious seed since the Neolithic and is cultivated for food in Asia. Water chestnut is now a species of conservation concern in Europe and Russia. Introduced to the northeastern United States in the mid-1800s, the spread of water chestnut as a nuisance weed was apparently favored by cultural eutrophication. Water chestnut is considered a pest in the U.S. because it forms extensive, dense beds in lakes, rivers, and freshwater-tidal habitats.

Synoptic review of the Literature on the southern oyster drill Thais haemastoma floridana

This literature search identifies a majority of the publications in the period 1880-1980 concerned with the marine gastropod, Thais haemastomafloridmul (Conrad). The southern oyster drill is an economically important oyster predator in the western Atlantic and Gulf of Mexico littoral. Major contributions of each paper to our knowledge of the drill's biology are briefly categorized. Hitherto unpublished research by the author on the snail's biology is documented. (PDF file contains 15 pages.)

Potential Application of Adsorptive Media to Enhance Phosphorus Uptake in Stormwater Basins and Wetlands at Lake Tahoe : literature review. Report to the University of California Davis Tahoe Research Group

Phosphorus removal by wetlands and basins in Lake Tahoe may be improved through designing these systems to filter storm water through media having higher phosphorus removal capabilities than local parent material. Substrates rich in iron, aluminum and calcium oftentimes have enhanced phosphorus removal. These substrates can be naturally occurring, byproducts of industrial or water treatment processes, or engineered. Phosphorus removal fundamentally occurs through chemical adsorption and/or precipitation and much of the phosphorus can be irreversibly bound. In addition to these standard media, other engineered substrates are available to enhance P removal. One such substrate is locally available in Reno and uses lanthanum coated diatomaceous earth for arsenate removal. This material, which has a high positive surface charge, can also irreversibly remove phosphorus. Physical factors also affect P removal. Specifically, specific surface area and particle shape affect filtration capacity, contact area between water and the surface area, and likelihood of clogging and blinding. A number of substrates have been shown to effectively remove P in case studies. Based upon these studies, promising substrates include WTRs, blast furnace slag, steel furnace slag, OPC, calcite, marble Utelite and other LWAs, zeolite and shale. However, other nonperformance factors such as environmental considerations, application logistics, costs, and potential for cementification narrow the list of possible media for application at Tahoe. Industrial byproducts such as slags risk possible leaching of heavy metals and this potential cannot be easily predicted. Fly ash and other fine particle substrates would be more difficult to apply because they would need to be blended, making them less desirable and more costly to apply than larger diameter media. High transportation costs rule out non-local products. Finally, amorphous calcium products will eventually cementify reducing their effectiveness in filtration systems. Based upon these considerations, bauxite, LWAs and expanded shales/clays, iron-rich sands, activated alumina, marble and dolomite, and natural and lanthanum activated diatomaceous earth are the products most likely to be tested for application at Tahoe. These materials are typically iron, calcium or aluminum based; many have a high specific surface area; and all have low transportation costs. (PDF contains 21 pages)

The contribution of fish intake, aquaculture, and small-scale fisheries to improving nutrition security: a literature review

Much of fish consumed by the poor are caught by household members and traded in local markets. These fish are rarely or poorly included in national statistics, and it is therefore difficult to estimate precisely the real contribution of fish to the rural poor households. This report is the first global overview of the role played by fish in improving nutrition. Fish consumption patterns of the poor, the nutritional value of fish, and small-scale fisheries and aquaculture activities are considered. It also highlights the gap in knowledge where more research is needed.

Techniques of producing monosex or sterile population of fish for aquaculture -- a review of selected literature

The need to develop techniques that can make the male grow faster in many species of fish as well as the female in some other species cannot be over-emphasized. Monosex culture of the faster growing sex can increase production if the method is reliable. The use of such techniques as manual sexing, sterilisation, hybridization, gynogenesis, androgenesis polyploidy and sex-reversal can provide solutions or partial solutions to the problems associated with sexual difference, sexual maturation and unwanted reproduction

Literature Review of Integrated Impact Assessment Models of Climate Change with Emphasis on Damage Functions

35 p.