Analysis of phase II metabolites of methamphetamine by solid-phase extraction and liquid chromatography with tandem mass spectrometric detection

Methamphetamine (METH) abuse is one of the most serious health problems in the United States and Europe due to its addictive properties and potential neurotoxic effects [1, 2, 3]. METH abuse appears to have stabilized or decreased slightly in the general populations, however abuse in certain populations is increasing [4, 5]. Treatments for drug abuse are often tested in animal behavioral pharmacology models. One of the first in vivo tests conducted in animals is to follow the concentration of the drug and its metabolites as a function of time. In this way, one can determine how long a potential medication must be active and one can decide if specific tissues are potentially better targets for medication

Discovery of novel reductive elimination pathway for 10-hydroxywarfarin

Coumadin (R/S-warfarin) anticoagulant therapy is highly efficacious in preventing the formation of blood clots; however, significant inter-individual variations in response risks over or under dosing resulting in adverse bleeding events or ineffective therapy, respectively. Levels of pharmacologically active forms of the drug and metabolites depend on a diversity of metabolic pathways. Cytochromes P450 play a major role in oxidizing R- and S-warfarin to 6-, 7-, 8-, 10-, and 4\u27-hydroxywarfarin, and warfarin alcohols form through a minor metabolic pathway involving reduction at the C11 position. We hypothesized that due to structural similarities with warfarin, hydroxywarfarins undergo reduction, possibly impacting their pharmacological activity and elimination. We modeled reduction reactions and carried out experimental steady-state reactions with human liver cytosol for conversion o

Discovery of the Mexican Blindcat, Prietella phreatophila, in the U.S., and an update on its rangewide conservation status

presented at the 2017 meeting of the Texas Academy of Science at Mary Hardin Baylor University, Belton, TexasMexican blindcat, Prietella phreatophila, was described in 1954 from a single locality in Northern Coahuila, México. Long listed as endangered by the Mexican federal government, it was listed by the U.S. Fish and Wildlife Service as a foreign endangered species in 1970, and the most recent (1996) update of its assessment for the IUCN Red List considers it endangered as well. Explorations in the late 1990s discovered many new localities extending nearly to the international border, and a captive population established provided insights into the species’ basic biology and behavior. In 2016 the species was discovered in a cave in the Amistad National Recreation Area (ANRA), just north of the Río Grande in Texas. The 1970 listing instantly gave the TX population full protection under the U.S. Endangered Species Act. The species’ subterranean and mostly inaccessible habitat endows it with extremely low detectability and its actual range is likely broader than physical sampling of specimens has revealed. We review all prior and new knowledge of the species and its habitat to provide an updated international reassessment of its overall conservation status and threats, which most notably include aquifer depletion and contamination in both the Mexican and U.S. portions of its known range. A live captive population of two specimens collected in 1997 in Coahuila and one Texas specimen is now at the San Antonio Zoo, we are working with NPS to further explore ANRA caves and hope eventually to return to Coahuila to more fully update the species’ conservation status.Integrative Biolog

Discovery of Endangered Mexican Blindcat, Prietella phreatophila, in Texas: Implications for International Groundwater Management and Evolution of the Regional Karst Aquifer Biota

Paper presented July 15, 2017 at the annual Joint Meeting of Ichthyologists and Herpetologists in Austin, Texas, USA (http://conferences.k-state.edu/JMIH-Austin-2017/). The oral presentation of this content mentioned questions about the taxonomy and phylogenetic position of Prietella lundbergi and the only specimens attributed to P. lundbergi apart from the holotype. Since the presentation, we obtained high resolution CT scans of both the holotype and a specimen (TNHC 25767) from Cueva del Nacimiento del Río Frio, not far north of the type locality. The anatomy revealed in those CT scans suggests that these specimens represent a single species, and that P. lundbergi is only remotely related to Prietella phreatophila, which would be consistent with results of Wilcox, T.P., F.J. Garcı́a de León, Dean A. Hendrickson, and D.M. Hillis. 2004. “Convergence among Cave Catfishes: Long-Branch Attraction and a Bayesian Relative Rates Test.” Molecular Phylogenetics and Evolution 31 (3): 1101–13. doi:10.1016/j.ympev.2003.11.006). Thus, further research is in progress by Hendrickson, Lundberg, Luckenbill and Arce that may result in taxonomic revision removing P. lundbergi from Prietella.Mexican blindcat, Prietella phreatophila, described in 1954 from a cave system near the town of Múzquiz in central Coahuila state, and considered a Mexican endemic, was listed by the U.S. Fish and Wildlife Service as a foreign endangered species (protected "wherever found") in 1970. Explorations in the 1990s discovered many new localities extending nearly to the international border, and in 2016 the species was discovered in Amistad National Recreation Area (ANRA) in Texas, just north of the international border near Del Rio. Not only does the discovery support the aquifer of this fish being an internationally shared resource, but the stygobitic invertebrate biota found with the fish indicates a potentially large extent of the aquifer, and thus possibly the fish, in Texas. Invertebrate faunal connections (historic or current) extend from the Amistad Lake area of the new occurrence west into the Trans-Pecos region and east into the Edwards Aquifer of central Texas. We explore implications of this for both water management and evolutionary history of this and other blind ictalurids, and suggest that population genetic studies of both stygobitic fishes and invertebrates could help hydrogeologists better define often difficult to map aquifer extents and interconnections. While NPS is continuing to support the cave explorations of ANRA that produced the Texas discovery, we propose a broader bi-national sampling effort for both the fish and invertebrates extending well beyond the current known distribution of P. phreatophila. We also pointed out questions about phylogenetic relatedness of P. phreatophila and P. lundbergi further south, as well as the possibility of a monophyletic clade of blindcats, including those of the Edwards Aquifer, Satan and Trogloglanis. If substantiated, that evolutionary history would imply broader historic inter-aquifer connections ranging from the San Antonio area as far south as southernmost Tamaulipas. Finally, we report establishment of a small captive population of Prietella phreatophila at San Antonio Zoo for research and possibly eventual conservation applications.U.S. National Park Service; San Antonio Zoo; University of Texas at Austin College of Natural Sciences and Department of Integrative BiologyIntegrative Biolog

Serum amyloid A (SAA): a novel biomarker for uterine serous papillary cancer

BACKGROUND: Uterine serous papillary carcinoma (USPC) is a biologically aggressive variant of endometrial cancer. We investigated the expression of Serum Amyloid A (SAA) and evaluated its potential as a serum biomarker in USPC patients. METHODS: SAA gene and protein expression levels were evaluated in USPC and normal endometrial tissues (NEC) by real-time PCR, immunohistochemistry (IHC), flow cytometry and by a sensitive bead-based immunoassay. SAA concentration in 123 serum samples from 51 healthy women, 42 women with benign diseases, and 30 USPC patients were also studied. RESULTS: SAA gene expression levels were significantly higher in USPC when compared with NEC (mean copy number by RT\u2013PCR\ubc162 vs 2.21; P\ubc0.0002). IHC revealed diffuse cytoplasmic SAA protein staining in USPC tissues. High intracellular levels of SAA were identified in primary USPC cell lines evaluated by flow cytometry and SAA was found to be actively secreted in vitro. SAA concentrations (mgml 1) had a median (95% CIs) of 6.0 (4.0\u20138.9) in normal healthy females and 6.0 (4.2\u20138.1) in patients with benign disease (P\ubc0.92). In contrast, SAA values in the serum of USPC patients had a median (95% CI) of 15.6 (9.2\u201356.2), significantly higher than those in the healthy group (P\ubc0.0005) and benign group (P\ubc0.0006). Receiver operating characteristics (ROC) analysis of serum SAA to classify advanced- and early-stage USPC yielded an area under the ROC curve of 0.837 (P\ubc0.0024). CONCLUSION: SAA is not only a liver-secreted protein but is also a USPC cell product. SAA may represent a novel biomarker for USPC to assist in staging patients preoperatively, and to monitor early-disease recurrence and response to therapy

Ellagic Acid Derivatives from Rubus ulmifolius Inhibit Staphylococcus aureus Biofilm Formation and Improve Response to Antibiotics

Biofilms contribute to the pathogenesis of many forms of Staphylococcus aureus infection. Treatment of these infections is complicated by intrinsic resistance to conventional antibiotics, thus creating an urgent need for strategies that can be used for the prevention and treatment of biofilm-associated infections.This study demonstrates that a botanical natural product composition (220D-F2) rich in ellagic acid and its derivatives can limit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility. The source of this composition is Rubus ulmifolius Schott. (Rosaceae), a plant used in complementary and alternative medicine in southern Italy for the treatment of skin and soft tissue infections. All S. aureus clonal lineages tested exhibited a reduced capacity to form a biofilm at 220D-F2 concentrations ranging from 50-200 µg/mL, which were well below the concentrations required to limit bacterial growth (530-1040 µg/mL). This limitation was therapeutically relevant in that inclusion of 220D-F2 resulted in enhanced susceptibility to the functionally-distinct antibiotics daptomycin, clindamycin and oxacillin. Testing with kidney and liver cell lines also demonstrated a lack of host cell cytotoxicity at concentrations of 220D-F2 required to achieve these effects.These results demonstrate that extract 220D-F2 from the root of Rubus ulmifolius can be used to inhibit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility without toxic effects on normal mammalian cells. Hence, 220D-F2 is a strong candidate for development as a botanical drug for use in the prevention and treatment of S. aureus biofilm-associated infections

Carbon dioxide reduction in the building life cycle: a critical review

The construction industry is known to be a major contributor to environmental pressures due to its high energy consumption and carbon dioxide generation. The growing amount of carbon dioxide emissions over buildings’ life cycles has prompted academics and professionals to initiate various studies relating to this problem. Researchers have been exploring carbon dioxide reduction methods for each phase of the building life cycle – from planning and design, materials production, materials distribution and construction process, maintenance and renovation, deconstruction and disposal, to the material reuse and recycle phase. This paper aims to present the state of the art in carbon dioxide reduction studies relating to the construction industry. Studies of carbon dioxide reduction throughout the building life cycle are reviewed and discussed, including those relating to green building design, innovative low carbon dioxide materials, green construction methods, energy efficiency schemes, life cycle energy analysis, construction waste management, reuse and recycling of materials and the cradle-to-cradle concept. The review provides building practitioners and researchers with a better understanding of carbon dioxide reduction potential and approaches worldwide. Opportunities for carbon dioxide reduction can thereby be maximised over the building life cycle by creating environmentally benign designs and using low carbon dioxide materials

Bioavailability of Macro and Micronutrients Across Global Topsoils: Main Drivers and Global Change Impacts

Understanding the chemical composition of our planet\u27s crust was one of the biggest questions of the 20th century. More than 100 years later, we are still far from understanding the global patterns in the bioavailability and spatial coupling of elements in topsoils worldwide, despite their importance for the productivity and functioning of terrestrial ecosystems. Here, we measured the bioavailability and coupling of thirteen macro- and micronutrients and phytotoxic elements in topsoils (3–8 cm) from a range of terrestrial ecosystems across all continents (∼10,000 observations) and in response to global change manipulations (∼5,000 observations). For this, we incubated between 1 and 4 pairs of anionic and cationic exchange membranes per site for a mean period of 53 days. The most bioavailable elements (Ca, Mg, and K) were also amongst the most abundant in the crust. Patterns of bioavailability were biome-dependent and controlled by soil properties such as pH, organic matter content and texture, plant cover, and climate. However, global change simulations resulted in important alterations in the bioavailability of elements. Elements were highly coupled, and coupling was predictable by the atomic properties of elements, particularly mass, mass to charge ratio, and second ionization energy. Deviations from the predictable coupling-atomic mass relationship were attributed to global change and agriculture. Our work illustrates the tight links between the bioavailability and coupling of topsoil elements and environmental context, human activities, and atomic properties of elements, thus deeply enhancing our integrated understanding of the biogeochemical connections that underlie the productivity and functioning of terrestrial ecosystems in a changing world