ASU Scholarship Showcase

Illicit psychostimulant addiction remains a significant problem worldwide, despite decades of research into the neural underpinnings and various treatment approaches. The purpose of this review is to provide a succinct overview of the neurocircuitry involved in drug addiction, as well as the acute and chronic effects of cocaine and amphetamines within this circuitry in humans. Investigational pharmacological treatments for illicit psychostimulant addiction are also reviewed. Our current knowledge base clearly demonstrates that illicit psychostimulants produce lasting adaptive neural and behavioral changes that contribute to the progression and maintenance of addiction. However, attempts at generating pharmacological treatments for psychostimulant addiction have historically focused on intervening at the level of the acute effects of these drugs. The lack of approved pharmacological treatments for psychostimulant addiction highlights the need for new treatment strategies, especially those that prevent or ameliorate the adaptive neural, cognitive, and behavioral changes caused by chronic use of this class of illicit drugs.

The World Health Organization recently proposed the inclusion of brominated congeners in addition to chlorinated congeners when computing the toxic equivalency (TEQ) of dioxin-like compounds (DLCs) in assessments of human health risks. In the present study, 12 polybrominated dibenzo-p-dioxins and furans (PBDD/Fs) were analyzed by gas chromatography/high resolution mass spectrometry in the composited, archived biosolids that were collected in 32 U.S. states and the District of Columbia from 94 wastewater treatment plants by the United States Environmental Protection Agency in its 2001 national sewage sludge survey. Two PBDDs and five PBDFs were detected in the biosolids composites at varying frequencies (40–100%) with a total mean concentration of 10,000 ng/kg dry weight (range: 630–42,800), of which 1,2,3,4,6,7,8-hepta-BDF constituted about 95% by mass. Relative to commercial polybrominated diphenyl ether (PBDE) formulations, the ratio of PBDD/Fs to PBDEs in biosolids was 55-times higher (∼0.002% vs ∼0.11%), which indicates potential PBDE transformation or possibly additional sources of PBDD/Fs in the environment. The TEQ contribution of PBDD/Fs was estimated at 162 ng/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (range: 15–672), which is equivalent to 75% (range: 12–96%) of the total TEQ in biosolids. The TEQ of DLCs released annually to U.S. soils as a result of the land application of biosolids was estimated at 720 g (range: 530–1600 g). Among all known DLCs determined in biosolids, brominated analogs contributed 370% more TEQ than did chlorinated congeners, which indicates the need to include brominated DLCs in the exposure and risk assessment of land-applied biosolids.

Widespread contamination of groundwater by chlorinated ethenes and their biological dechlorination products necessitates the reliable monitoring of liquid matrices; current methods approved by the U.S. Environmental Protection Agency (EPA) require a minimum of 5 mL of sample volume and cannot simultaneously detect all transformative products. This paper reports on the simultaneous detection of six chlorinated ethenes and ethene itself, using a liquid sample volume of 1 mL by concentrating the compounds onto an 85-µm carboxen-polydimenthylsiloxane solid-phase microextraction fiber in 5 min and subsequent chromatographic analysis in 9.15 min. Linear increases in signal response were obtained over three orders of magnitude (∼0.05 to ∼50 µM) for simultaneous analysis with coefficient of determination (R²) values of ≥ 0.99. The detection limits of the method (1.3–6 µg/L) were at or below the maximum contaminant levels specified by the EPA. Matrix spike studies with groundwater and mineral medium showed recovery rates between 79–108%. The utility of the method was demonstrated in lab-scale sediment flow-through columns assessing the bioremediation potential of chlorinated ethene-contaminated groundwater. Owing to its low sample volume requirements, good sensitivity and broad target analyte range, the method is suitable for routine compliance monitoring and is particularly attractive for interpreting the bench-scale feasibility studies that are commonly performed during the remedial design stage of groundwater cleanup projects.

Attention deficit/hyperactivity disorder (ADHD) is a risk factor for tobacco use and dependence. This study examines the responsiveness to nicotine of an adolescent model of ADHD, the spontaneously hypertensive rat (SHR). The conditioned place preference (CPP) procedure was used to assess nicotine-induced locomotion and conditioned reward in SHR and the Wistar Kyoto (WKY) control strain over a range of nicotine doses (0.0, 0.1, 0.3 and 0.6 mg/kg). Prior to conditioning, SHRs were more active and less biased toward one side of the CPP chamber than WKY rats. Following conditioning, SHRs developed CPP to the highest dose of nicotine (0.6 mg/kg), whereas WKYs did not develop CPP to any nicotine dose tested. During conditioning, SHRs displayed greater locomotor activity in the nicotine-paired compartment than in the saline-paired compartment across conditioning trials. SHRs that received nicotine (0.1, 0.3, 0.6 mg/kg) in the nicotine-paired compartment showed an increase in locomotor activity between conditioning trials. Nicotine did not significantly affect WKY locomotor activity. These findings suggest that the SHR strain is a suitable model for studying ADHD-related nicotine use and dependence, but highlights potential limitations of the WKY control strain and the CPP procedure for modeling ADHD-related nicotine reward.

Important antibiotics in human medicine have been used for many decades in animal agriculture for growth promotion and disease treatment. Several publications have linked antibiotic resistance development and spread with animal production. Aquaculture, the newest and fastest growing food production sector, may promote similar or new resistance mechanisms. This review of 650+ papers from diverse sources examines parallels and differences between land-based agriculture of swine, beef, and poultry and aquaculture. Among three key findings was, first, that of 51 antibiotics commonly used in aquaculture and agriculture, 39 (or 76%) are also of importance in human medicine; furthermore, six classes of antibiotics commonly used in both agriculture and aquaculture are also included on the World Health Organization’s (WHO) list of critically important/highly important/important antimicrobials. Second, various zoonotic pathogens isolated from meat and seafood were observed to feature resistance to multiple antibiotics on the WHO list, irrespective of their origin in either agriculture or aquaculture. Third, the data show that resistant bacteria isolated from both aquaculture and agriculture share the same resistance mechanisms, indicating that aquaculture is contributing to the same resistance issues established by terrestrial agriculture. More transparency in data collection and reporting is needed so the risks and benefits of antibiotic usage can be adequately assessed.

A meta-analysis was conducted to inform the epistemology, or theory of knowledge, of contaminants of emerging concern (CECs). The CEC terminology acknowledges the existence of harmful environmental agents whose identities, occurrences, hazards, and effects are not sufficiently understood. Here, data on publishing activity were analyzed for 12 CECs, revealing a common pattern of emergence, suitable for identifying past years of peak concern and forecasting future ones: dichlorodiphenyltrichloroethane (DDT; 1972, 2008), trichloroacetic acid (TCAA; 1972, 2009), nitrosodimethylamine (1984), methyl tert-butyl ether (2001), trichloroethylene (2005), perchlorate (2006), 1,4-dioxane (2009), prions (2009), triclocarban (2010), triclosan (2012), nanomaterials (by 2016), and microplastics (2022 ± 4). CECs were found to emerge from obscurity to the height of concern in 14.1 ± 3.6 years, and subside to a new baseline level of concern in 14.5 ± 4.5 years. CECs can emerge more than once (e.g., TCAA, DDT) and the multifactorial process of emergence may be driven by inception of novel scientific methods (e.g., ion chromatography, mass spectrometry and nanometrology), scientific paradigm shifts (discovery of infectious proteins), and the development, marketing and mass consumption of novel products (antimicrobial personal care products, microplastics and nanomaterials). Publishing activity and U.S. regulatory actions were correlated for several CECs investigated.

Processed municipal sewage sludges (MSS) are an abundant, unwanted by-product of wastewater treatment, increasingly applied to agriculture and forestry for inexpensive disposal and soil conditioning. Due to their high organic carbon and lipid contents, MSS not only is rich in carbon and nutrients but also represents a “sink” for recalcitrant, hydrophobic, and potentially bioaccumulative compounds. Indeed, many organics sequestered and concentrated in MSS meet the US Environmental Protection Agency’s definition of being persistent, bioaccumulative, and toxic (PBT). In a strategic effort, our research team at the Biodesign Institute has created the National Sewage Sludge Repository (NSSR), a large repository of digested MSSs from 164 wastewater treatment plants from across the USA, as part of the Human Health Observatory (H2O) at Arizona State University (ASU). The NSSR likely represents the largest archive of digested MSS specimens in the USA. The present study summarizes key findings gleaned thus far from analysis of NSSR samples. For example, we evaluated the content of toxicants in MSS and computed estimates of nationwide inventories of mass produced chemicals that become sequestrated in sludge and later are released into the environment during sludge disposal on land. Ongoing efforts document co-occurrence of a variety of PBT compounds in both MSS and human samples, while also identifying a large number of potentially harmful MSS constituents for which human exposure data are still lacking. Finally, we summarize future opportunities and invite collaborative use of the NSSR by the research community. The H2O at ASU represents a new resource and research tool for environmental scientists and the larger research community. As illustrated in this work, this repository can serve to (i) identify and prioritize emerging contaminants, (ii) provide spatial and temporal trends of contaminants, (iii) inform and evaluate the effectiveness of environmental policy-making and regulations, and (iv) approximate, ongoing exposures and body burdens of mass-produced chemicals in human society.

Although insulin resistance in skeletal muscle is well-characterized, the role of circulating whole blood in the metabolic syndrome phenotype is not well understood. We set out to test the hypothesis that genes involved in inflammation, insulin signaling and mitochondrial function would be altered in expression in the whole blood of individuals with metabolic syndrome. We further wanted to examine whether similar relationships that we have found previously in skeletal muscle exist in peripheral whole blood cells. All subjects (n=184) were Latino descent from the Arizona Insulin Resistance registry. Subjects were classified based on the metabolic syndrome phenotype according to the National Cholesterol Education Program’s Adult Treatment Panel III. Of the 184 Latino subjects in the study, 74 were classified with the metabolic syndrome and 110 were without. Whole blood gene expression profiling was performed using the Agilent 4x44K Whole Human Genome Microarray. Whole blood microarray analysis identified 1,432 probes that were altered in expression ≥1.2 fold and P<0.05 after Benjamini-Hochberg in the metabolic syndrome subjects. KEGG pathway analysis revealed significant enrichment for pathways including ribosome, oxidative phosphorylation and MAPK signaling (all Benjamini-Hochberg P<0.05). Whole blood mRNA expression changes observed in the microarray data were confirmed by quantitative RT-PCR. Transcription factor binding motif enrichment analysis revealed E2F1, ELK1, NF-kappaB, STAT1 and STAT3 significantly enriched after Bonferroni correction (all P<0.05). The results of the present study demonstrate that whole blood is a useful tissue for studying the metabolic syndrome and its underlying insulin resistance although the relationship between blood and skeletal muscle differs.

Positive allosteric modulators (PAMs) of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are a diverse class of compounds that increase fast excitatory transmission in the brain. AMPA PAMs have been shown to facilitate long-term potentiation, strengthen communication between various cortical and subcortical regions, and some of these compounds increase the production and release of brain-derived neurotrophic factor (BDNF) in an activity-dependent manner. Through these mechanisms, AMPA PAMs have shown promise as broad spectrum pharmacotherapeutics in preclinical and clinical studies for various neurodegenerative and psychiatric disorders. In recent years, a small collection of preclinical animal studies has also shown that AMPA PAMs may have potential as pharmacotherapeutic adjuncts to extinction-based or cue-exposure therapies for the treatment of drug addiction. The present paper will review this preclinical literature, discuss novel data collected in our laboratory, and recommend future research directions for the possible development of AMPA PAMs as anti-addiction medications.

Perchloroethylene (PCE) is a highly utilized solvent in the dry cleaning industry because of its cleaning effectiveness and relatively low cost to consumers. According to the 2006 U.S. Census, approximately 28,000 dry cleaning operations used PCE as their principal cleaning agent. Widespread use of PCE is problematic because of its adverse impacts on human health and environmental quality. As PCE use is curtailed, effective alternatives must be analyzed for their toxicity and impacts to human health and the environment. Potential alternatives to PCE in dry cleaning include dipropylene glycol n-butyl ether (DPnB) and dipropylene glycol tert-butyl ether (DPtB), both promising to pose a relatively smaller risk. To evaluate these two alternatives to PCE, we established and scored performance criteria, including chemical toxicity, employee and customer exposure levels, impacts on the general population, costs of each system, and cleaning efficacy. The scores received for PCE were 5, 5, 3, 5, 3, and 3, respectively, and DPnB and DPtB scored 3, 1, 2, 2, 4, and 4, respectively. An aggregate sum of the performance criteria yielded a favorably low score of “16” for both DPnB and DPtB compared to “24” for PCE. We conclude that DPnB and DPtB are preferable dry cleaning agents, exhibiting reduced human toxicity and a lesser adverse impact on human health and the environment compared to PCE, with comparable capital investments, and moderately higher annual operating costs.