Pharmacology, Toxicology and Environmental Health Commons^™

Developmental Origins Of Cardiovascular Disease: Impact Of Early Life Stress In Humans And Rodents, Margaret O. Murphy, Dianne M. Cohn, Analia S. Loria

Pharmacology and Nutritional Sciences Faculty Publications

The Developmental Origins of Health and Disease (DOHaD) hypothesizes that environmental insults during childhood programs the individual to develop chronic disease in adulthood. Emerging epidemiological data strongly supports that early life stress (ELS) given by the exposure to adverse childhood experiences is regarded as an independent risk factor capable of predicting future risk of cardiovascular disease. Experimental animal models utilizing chronic behavioral stress during postnatal life, specifically maternal separation (MatSep) provides a suitable tool to elucidate molecular mechanisms by which ELS increases the risk to develop cardiovascular disease, including hypertension. The purpose of this review is to highlight current epidemiological …

Students Can Be Important Link Between Academia And Practice, Jason W. Marion, Charles D. Treser

EKU Faculty and Staff Scholarship

Editor’s Note: In an effort to promote the growth of the environmental health profession and the academic programs that fuel that growth, NEHA has teamed up with the Association of Environmental Health Academic Programs (AEHAP) to publish two columns a year in the Journal. AEHAP’s mission is to support environmental health education to ensure the optimal health of people and the environment. The organization works hand in hand with the National Environmental Health Science and Protection Accreditation Council (EHAC) to accredit, market, and promote EHAC-accredited environmental health degree programs. AEHAP focuses on increasing the environmental health workforce, supporting students and …

Neurotensin Nts1 And Nts2 Receptor Agonists Produce Anxiolytic-Like Effects In The 22-Khz Ultrasonic Vocalization Model In Rats, Floyd F. Steele Iii, Shannon C. Whitehouse, Jacob S. Aday, Adam J. Prus

Journal Articles

Neurotensin is a neuropeptide neurotransmitter that interacts with multiple neurotransmitter systems, including those regulating amygdalar function, via NTS₁ and NTS₂ receptors. Both receptors are expressed in the amygdala and agonists for NTS₁ or NTS₂ receptors have exhibited anxiolytic effects in animal models. Systemic adminstration of NTS₁ receptor agonist PD149163 was recently shown to reduce footshock conditioned 22-kHz ultrasonic vocalizations in rats, suggesting that PD149163 produced an anxiolytic effect. The effects that neurotensin may have or a selective NTS₂receptor agonist may have on 22-kHz vocalizations has yet to be examined. The current study evaluated …

Characterization Of Pit Latrines To Support The Design And Selection Of Emptying Tools In Peri-Urban Mzuzu, Malawi., Rashid Chiposa, Rochelle H. Holm, Chimuleke Munthali, Russel C.G. Chidya, Francis L. De Los Reyes

Faculty and Staff Scholarship

The urban areas of many low-income countries must balance a rising demand for pit latrines for household sanitation provision against limitations in space, resulting in a need for pit latrine emptying services. This study was undertaken in the peri-urban neighborhood of Area 1B in the city of Mzuzu, Malawi, to examine the characteristics of household pit latrines for designing and selecting pit latrine emptying tools. We used 150 structured household surveys and field observations. From this, a subset was selected and 30 manual cone penetrometer tests were conducted at full latrines. Chemical oxygen demand analysis was also performed for 14 …

Identification And Characterization Of Microrna Differentially Expressed In Macrophages Exposed To Porphyromonas Gingivalis Infection, Olivier Huck, J Al-Hashemi, L Poidevin, O Poch, J Davideau, H Tenenbaum, Salomon Amar

NYMC Faculty Publications

MicroRNAs (miRNAs) are short, noncoding RNAs involved in the regulation of several processes associated with inflammatory diseases and infection. Bacterial infection modulates miRNA expression to subvert any innate immune response. In this study we analyzed, using microarray analysis, the bacterial modulation of miRNAs in bone marrow-derived macrophages (BMMs) in which activity was induced by infection with Porphyromonas gingivalis The expression of several miRNAs was modulated 3 h postinfection (at a multiplicity of infection of 25). A bioinformatic analysis was performed to further identify pathways related to the innate immune host response under the influence of selected miRNAs. To assess the …

Effect Of Systemic Antioxidant Allopurinol Therapy On Skin Flap Survival, M Ardakani, Kaveh Alizadeh, A Moghadam

NYMC Faculty Publications

No abstract provided.

Calcium's Role As Nuanced Modulator Of Cellular Physiology In The Brain, Hilaree N. Frazier, Shaniya Maimaiti, Katie L. Anderson, Lawrence D. Brewer, John C. Gant, Nada M. Porter, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

Neuroscientists studying normal brain aging, spinal cord injury, Alzheimer’s disease (AD) and other neurodegenerative diseases have focused considerable effort on carefully characterizing intracellular perturbations in calcium dynamics or levels. At the cellular level, calcium is known for controlling life and death and orchestrating most events in between. For many years, intracellular calcium has been recognized as an essential ion associated with nearly all cellular functions from cell growth to degeneration. Often the emphasis is on the negative impact of calcium dysregulation and the typical worse-case-scenario leading inevitably to cell death. However, even high amplitude calcium transients, when executed acutely can …

A Blueprint To Evaluate One Health, Simon R. Rüegg, Barry J. Mcmahon, Barbara Häsler, Roberto Esposito, Helen O'Shea, Et Al

Department of Biological Sciences Publications

One Health (OH) positions health professionals as agents for change and provides a platform to manage determinants of health that are often not comprehensively captured in medicine or public health alone. However, due to the organization of societies and disciplines, and the sectoral allocation of resources, the development of transdisciplinary approaches requires effort and perseverance. Therefore, there is a need to provide evidence on the added value of OH for governments, researchers, funding bodies, and stakeholders. This paper outlines a conceptual framework of what OH approaches can encompass and the added values they can provide. The framework was developed during …

Dub3 Inhibition Suppresses Breast Cancer Invasion And Metastasis By Promoting Snail1 Degradation, Yadi Wu, Yu Wang, Yiwei Lin, Yajuan Liu, Yifan Wang, Jianhang Jia, Puja Singh, Young-In Chi, Chi Wang, Chenfang Dong, Wei Li, Min Tao, Dana L. Napier, Qiuying Shi, Jiong Deng, B. Mark Evers, Binhua P. Zhou

Pharmacology and Nutritional Sciences Faculty Publications

Snail1, a key transcription factor of epithelial–mesenchymal transition (EMT), is subjected to ubiquitination and degradation, but the mechanism by which Snail1 is stabilized in tumours remains unclear. We identify Dub3 as a bona fide Snail1 deubiquitinase, which interacts with and stabilizes Snail1. Dub3 is overexpressed in breast cancer; knockdown of Dub3 resulted in Snail1 destabilization, suppressed EMT and decreased tumour cell migration, invasion, and metastasis. These effects are rescued by ectopic Snail1 expression. IL-6 also stabilizes Snail1 by inducing Dub3 expression, the specific inhibitor WP1130 binds to Dub3 and inhibits the Dub3-mediating Snail1 stabilization in vitroand in vivo. …

Niche By Basma Kavanagh, Vivian M. Hansen

The Goose

Review of Basma Kavanagh's Niche.

M2 Polarization Of Macrophages Facilitates Arsenic-Induced Cell Transformation Of Lung Epithelial Cells, Jiajun Cui, Wenhua Xu, Jian Chen, Hui Li, Lu Dai, Jacqueline A. Frank, Shaojun Peng, Siying Wang, Gang Chen

Pharmacology and Nutritional Sciences Faculty Publications

The alterations in microenvironment upon chronic arsenic exposure may contribute to arsenic-induced lung carcinogenesis. Immune cells, such as macrophages, play an important role in mediating the microenvironment in the lungs. Macrophages carry out their functions after activation. There are two activation status for macrophages: classical (M1) or alternative (M2); the latter is associated with tumorigenesis. Our previous work showed that long-term arsenic exposure induces transformation of lung epithelial cells. However, the crosstalk between epithelial cells and macrophages upon arsenic exposure has not been investigated. In this study, using a co-culture system in which human lung epithelial cells are cultured with …

Pit Latrine Fecal Sludge Resistance Using A Dynamic Cone Penetrometer In Low Income Areas In Mzuzu City, Malawi., Charles F.C. Chirwa, Ralph P. Hall, Leigh Anne H. Krometis, Eric A. Vance, Adam Edwards, Ting Guan, Rochelle H. Holm

Faculty and Staff Scholarship

Pit latrines can provide improved household sanitation, but without effective and inexpensive emptying options, they are often abandoned once full and may pose a public health threat. Emptying techniques can be difficult, as the sludge contents of each pit latrine are different. The design of effective emptying techniques (e.g., pumps) is limited by a lack of data characterizing typical in situ latrine sludge resistance. This investigation aimed to better understand the community education and technical engineering needs necessary to improve pit latrine management. In low income areas within Mzuzu city, Malawi, 300 pit latrines from three distinct areas were assessed …

Genetic Targeting In Cerebellar Purkinje Cells: An Update., Anna Sługocka, Jan Wiaderkiewicz, Jaroslaw J Barski

Pharmacology and Physiology Faculty Publications

Since the last review paper published in Cerebellum in 2002 [1], there has been a substantial increase in the number of experiments utilizing transgenic manipulations in murine cerebellar Purkinje cells. Most of these approaches were made possible with the use of the Cre/loxP methodology and pcp2/L7 based Cre recombinase expressing transgenic mouse strains. This review aims to summarize all studies which used Purkinje cell specific transgenesis since the first use of mouse strain with Purkinje cell specific Cre expression in 2002.

Assessment Of Childhood Domestic Injuries Among Joint And Nuclear Families Of Karachi, Asif Khaliq, Amreen Rao, Shahroz Siddiqui, Ghulam Mujtaba Nasir

Department of Biological & Biomedical Sciences

To assess the frequencies and factors of domestic injuries among children aged less than 5 years. This is a cross sectional study, in which parents who have child less than 5 years of age were targeted. A total of 246 participants had provided satisfactory information and they were approached by non-probability purposive sampling technique from January 2016 to June 2016. The data was entered in Excel and then imported to SPSS 19.0 for inferential analysis. In this study, 89.8% (n = 221) mothers and 10.2% (n = 25) father who had participated. 52.08% (n = 123) parents were from joint …

Impact Of Urbanization On Temperature Variation In Big Cities: Measuring Health Risk While Targeting Vulnerable Population, Maryam E. Karimi

Dissertations, Theses, and Capstone Projects

Densely populated cities are experiencing Urban Heat Island (UHI) effects and localized hotspots. Cities, such as New York can form heat islands all year round. This is primarily due to land surface modifications, radiative trapping in urban canyons and lack of cooling through evapotranspiration caused by displaced trees and vegetation. UHI refers to an increase in air and surface temperature in cities compared to surrounding suburban and rural areas. Large scale environmental forcing can cause subdivisions of UHI throughout a city. The combined of environmental forcing effects lead to the formation of hot pockets within the cities at micro-scale. The …

Inhibition Of The Integrin/Fak Signaling Axis And C-Myc Synergistically Disrupts Ovarian Cancer Malignancy, B. Xu, Jason R. Lefringhouse, Z. Liu, D. West, Lauren A. Baldwin, C. Ou, L. Chen, Dana L. Napier, Luksana Chaiswing, Lawrence D. Brewer, Daret K. St Clair, Olivier Thibault, John R. Van Nagell, Binhua P. Zhou, R. Drapkin, J.-A. Huang, M. L. Lu, Frederick R. Ueland, X. H. Yang

Pharmacology and Nutritional Sciences Faculty Publications

Integrins, a family of heterodimeric receptors for extracellular matrix, are promising therapeutic targets for ovarian cancer, particularly high-grade serous-type (HGSOC), as they drive tumor cell attachment, migration, proliferation and survival by activating focal adhesion kinase (FAK)-dependent signaling. Owing to the potential off-target effects of FAK inhibitors, disruption of the integrin signaling axis remains to be a challenge. Here, we tackled this barrier by screening for inhibitors being functionally cooperative with small-molecule VS-6063, a phase II FAK inhibitor. From this screening, JQ1, a potent inhibitor of Myc oncogenic network, emerged as the most robust collaborator. Treatment with a combination of VS-6063 …

Sodium-Myoinositol Cotransporter-1, Smit1, Mediates The Production Of Reactive Oxygen Species Induced By Hyperglycemia In The Heart, Anne Van Steenbergen, Magali Balteau, Audrey Ginion, Laura Ferté, Sylvain Battault, Christophe De Meester De Ravenstein, Jean-Luc Balligand, Evangelos-Panagiotis Daskalopoulos, Patrick Gilon, Florin Despa, Sanda Despa, Jean-Louis Vanoverschelde, Sandrine Horman, Hermann Koepsell, Gerard Berry, Louis Hue, Luc Bertrand, Christophe Beauloye

Pharmacology and Nutritional Sciences Faculty Publications

Hyperglycemia (HG) stimulates the production of reactive oxygen species in the heart through activation of NADPH oxidase 2 (NOX2). This production is independent of glucose metabolism but requires sodium/glucose cotransporters (SGLT). Seven SGLT isoforms (SGLT1 to 6 and sodium-myoinositol cotransporter-1, SMIT1) are known, although their expression and function in the heart remain elusive. We investigated these 7 isoforms and found that only SGLT1 and SMIT1 were expressed in mouse, rat and human hearts. In cardiomyocytes, galactose (transported through SGLT1) did not activate NOX2. Accordingly, SGLT1 deficiency did not prevent HG-induced NOX2 activation, ruling it out in the cellular response to …

Translational Models For Vascular Cognitive Impairment: A Review Including Larger Species, Atticus H. Hainsworth, Stuart M. Allan, Johannes Boltze, Catriona Cunningham, Chad Farris, Elizabeth Head, Masafumi Ihara, Jeremy D. Isaacs, Raj N. Kalaria, Saskia A. M. J. Lesnik Oberstein, Mark B. Moss, Björn Nitzsche, Gary A. Rosenberg, Julie W. Rutten, Melita Salkovic-Petrisic, Aron M. Troen

Pharmacology and Nutritional Sciences Faculty Publications

Background: Disease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015). Only peer-reviewed sources were cited.

Methods: We included models that mimic VCI-related brain lesions (white matter hypoperfusion injury, focal ischaemia, cerebral amyloid angiopathy) or reproduce VCI risk factors (old age, hypertension, …

Occupational Styrene Exposure On Auditory Function Among Adults: A Systematic Review Of Selected Workers, Francis T. Pleban, Olutosin Oketope, Laxmi Shrestha

Public Health, Health Administration, and Health Sciences Faculty Research

A review study was conducted to examine the adverse effects of styrene, styrene mixtures, or styrene and/or styrene mixtures and noise on the auditory system in humans employed in occupational settings. The search included peer-reviewed articles published in English language involving human volunteers spanning a 25-year period (1990–2015). Studies included peer review journals, case–control studies, and case reports. Animal studies were excluded. An initial search identified 40 studies. After screening for inclusion, 13 studies were retrieved for full journal detail examination and review. As a whole, the results range from no to mild associations between styrene exposure and auditory dysfunction, …

Chloroquine-Inducible Par-4 Secretion Is Essential For Tumor Cell Apoptosis And Inhibition Of Metastasis, Ravshan Burikhanov, Nikhil Hebbar, Sunil K. Noothi, Nidhi Shukla, James Sledziona, Nathália Araujo, Meghana Kudrimoti, Qing Jun Wang, David S. Watt, Danny R. Welch, Jodi Maranchie, Akihiro Harada, Vivek M. Rangnekar

Radiation Medicine Faculty Publications

The induction of tumor suppressor proteins capable of cancer cell apoptosis represents an attractive option for the re-purposing of existing drugs. We report that the anti-malarial drug, chloroquine (CQ), is a robust inducer of Par-4 secretion from normal cells in mice and cancer patients in a clinical trial. CQ-inducible Par-4 secretion triggers paracrine apoptosis of cancer cells and also inhibits metastatic tumor growth. CQ induces Par-4 secretion via the classical secretory pathway that requires the activation of p53. Mechanistically, p53 directly induces Rab8b, a GTPase essential for vesicle transport of Par-4 to the plasma membrane prior to secretion. Our findings …