Chemicals and Drugs Commons^™

"It’S Just Another Thing”: Perceptions Of Well Water Quality And Barriers In An Arsenic Hot Spot, Linzy Rosen

Honors Theses

Privately owned water is the primary source of drinking water for 43 million Americans. Although residential or private wells are susceptible to a variety of contaminants, the Safe Drinking Water Act of 1974 positions individuals as responsible for the testing, remediation, and management of this water. Despite the elevated presence of arsenic in Maine, which is linked to various cancers, cardiovascular disease, and neurological damage, little is known about how private well owners perceive the safety and quality of their own water.

This study takes a qualitative approach to understanding concerns and opinions by conducting semi - structured interviews with …

Investigating The Mitochondrial Protein Mitoneet In C. Elegans Models Of Aging And Alzheimer's Disease, Jacob Ryan Boos

Graduate Theses, Dissertations, and Problem Reports

Oxidative stress is an imbalance between reactive oxygen species production and elimination, favoring the former. Reactive oxygen species serve as important signaling molecules for physiological homeostasis. However, when produced in excess, these once important signaling molecules become detrimental, disrupting cellular functions, and ultimately leading to cell death. In aging, reactive oxygen species production is increased, accompanied with reductions in oxidative stress resistance, increasing the risk for developing age-related diseases including cardiovascular disease, cancer, stroke, and neurodegenerative diseases. The outer mitochondrial membrane iron-sulfur cluster containing protein mitoNEET (CISD1; gene CISD1) has shown to be a mediator of mitochondrial function and …

Management Of Adult Growth Hormone Deficiency Related To Hypopituitarism, Kellie Jamin

Capstone Showcase

The treatment of growth hormone deficiency (GHD) is well-established in childhood but less understood in adults, given the more complex role that growth hormone (GH) assumes in this population. Decreased functionality of the pituitary gland, otherwise known as hypopituitarism, can present with an isolated GHD in adulthood, which may result from a number of factors including neoplasm, ischemia, infection, traumatic injury, or systemic disease. Adult GHD may be definitively diagnosed with a stimulation test, the insulin tolerance test (ITT) being the study of choice. With a positive ITT, the disorder can be treated with growth hormone replacement therapy (GHRT), which …

Safety, Efficacy, And Reversibility Of Novel Male Contraceptives For Improved Pregnancy Prevention, Danielle Anton

Capstone Showcase

Unintended pregnancy is a global issue that can result from contraceptive failure or from a lack of contraceptive use. A literature search was conducted to explore novel methods of male contraceptives being developed for improved pregnancy prevention. Seven articles were selected, reporting on either oral contraceptive pills, transdermal gel, injectable hormonal, or bilateral intravas deferens polymer injection. The most common adverse events reported across all studies include changes in libido, mood, weight gain, acne, and headache. After reaching hormone and sperm concentration levels sufficient for pregnancy prevention, authors reported complete reversibility of contraceptive effects. Four studies described changes in various …

Is The Precipitation Of Anxiety Symptoms Associated With Bolus Doses Of Flumazenil A Barrier To Its Use At Low Continuous Doses In Benzodiazepine Withdrawal?, Alexander Gallo, Tim Macdonald, Kellie Bennett, Gioiamia Basso-Hulse, Gary Hulse

Research outputs 2022 to 2026

Introduction:

Benzodiazepines (BZDs) are used in the management of anxiety and sleep disorders; however, chronic use is associated with tolerance and dependence. During withdrawal, symptoms of anxiety are often severe and problematic for patients and may lead to relapse or maintenance on low doses of BZDs. Low, continuous doses of flumazenil reduce BZD withdrawal symptoms in several studies; however, bolus doses are known to induce anxiety and precipitate panic. Accordingly, this study aimed to determine whether continuous low-dose flumazenil is anxiogenic like bolus doses.

Method:

In a randomised control cross over design, participants received a continuous low-dose flumazenil infusion for …

A Study Of Cobalt (Iii) Oxide Nanoparticle Delivery Of Sirna Molecules Directed Against Signaling Intermediates Of The P2y2 Receptor, Rachel Blair Stroud

MSU Graduate Theses

G protein-coupled receptors are evolutionarily ubiquitous sensors of extracellular signals, propagating intracellular signal cascades through heterotrimeric G proteins. P2Y₂ receptors are GPCRs which are activated by extracellular nucleotides to mediate signaling cascades via Gαq coupling. Many GPCRs are subject to a common mechanism for signal termination involving phosphorylation of the C-terminal tail followed by β-arrestin binding and subsequent endocytic internalization of the complex. This effect has been described for the P2Y₂ R in the 1321N1 astrocytoma cell line, and UTP-induced activation and desensitization profiles have been previously defined. There is need to develop molecular vehicles for safe and …

Characterization Of Nanoparticles Using Inductively-Coupled Plasma Mass Spectrometry, Jabez D. Campbell

MSU Graduate Theses

Nanomaterials are a relatively new class of materials that have many applications which span a wide host of fields from medical products to consumer products. The possible compositions and forms of nanomaterials are just as varied as the applications. Therefore, a versatile characterization method is needed for researchers and regulators alike to ensure nanomaterials are properly used. Single Particle Inductively Coupled Plasma Mass Spectrometry (SP-ICP-MS) is a functional method that could fill the characterization need in the nanomaterial research field. Using data from both SP-ICP-MS tests and data from literature established characterization methods, the viability of making SP-ICP-MS the standard …

Effectiveness Of Stabilized Hypochlorous Acid In Acute Peritonitis Treatment: A Murine Surgical Study, Benjamin Michael Pomeroy

MSU Graduate Theses

Peritonitis is an inflammatory condition affecting the mesothelial cells that line the peritoneal cavity and is commonly induced by bowel perforations. This medical emergency is treated through antibiotic therapy and surgical intervention followed by tissue irrigation (lavage). Acute treatments aim to remove the bacterial burden, however recurring peritoneal infections occur at high rates and contribute to patient morbidity. These recurring infections are likely due to the inability of lavage solutions to remove the entire massive intra-abdominal bacterial load due to intestinal perforation. Numerous antiseptic solutions and antibiotic additives have been evaluated in their ability to improve source control by abdominal …

Mechanism For Selective Binding Of Aromatic Compounds On Oxygen-Rich Graphene Nanosheets Based On Molecule Size/Polarity Matching, Heyun Fu, Bingyu Wang, Dongqiang Zhu, Zhicheng Zhou, Shidong Bao, Xiaolei Qu, Yong Guo, Lan Ling, Shourong Zheng, Pu Duan, Jingdong Mao, Klaus Schmidt-Rohr, Shu Tao, Pedro J.J. Alvarez

Chemistry & Biochemistry Faculty Publications

Selective binding of organic compounds is the cornerstone of many important industrial and pharmaceutical applications. Here, we achieved highly selective binding of aromatic compounds in aqueous solution and gas phase by oxygen-enriched graphene oxide (GO) nanosheets via a previously unknown mechanism based on size matching and polarity matching. Oxygen-containing functional groups (predominately epoxies and hydroxyls) on the nongraphitized aliphatic carbons of the basal plane of GO formed highly polar regions that encompass graphitic regions slightly larger than the benzene ring. This facilitated size match–based interactions between small apolar compounds and the isolated aromatic region of GO, resulting in high binding …

European Epidemiological Patterns Of Cannabis- And Substance-Related Body Wall Congenital Anomalies: Geospatiotemporal And Causal Inferential Study, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

As body wall congenital anomalies (BWCAs) have a long history of being associated with prenatal or community cannabis exposure (CCE), it was of interest to investigate these epidemiological relationships in Europe given the recent increases in cannabis use prevalence, daily intensity, and Δ9-tetrahydrocannabinol (THC) potency. Methods: This study makes use of BWCA data from Eurocat, drug exposure data from the European Monitoring Centre for Drugs and Drug Addiction, and income from the World Bank. Results: The mapping analysis showed that BWCARs increased in France, Spain, and the Netherlands. The bivariate mapping analysis showed that the BWCA rates (BWCAR) and the …

Activity Of Newest Generation Β-Lactam/Β-Lactamase Inhibitor Combination Therapies Against Multidrug Resistant Pseudomonas Aeruginosa, Robbie R. Haines, Papanin Putsathit, Katherine A. Hammer, Anna S. Tai

Research outputs 2022 to 2026

Multidrug resistant (MDR) P. aeruginosa accounts for 35 % of all P. aeruginosa isolated from respiratory samples of patients with cystic fibrosis (CF). The usefulness of β-lactam antibiotics for treating CF, such as carbapenems and later generation cephalosporins, is limited by the development of antibacterial resistance. A proven treatment approach is the combination of a β-lactam antibiotic with a β-lactamase inhibitor. New β-lactam/β-lactamase inhibitor combinations are available, but data are lacking regarding the susceptibility of MDR CF-associated P. aeruginosa (CFPA) to these new combination therapies. In this study we determined MIC values for three new combinations; imipenem-relebactam (I-R), ceftazidime-avibactam (CZA), …

Personalised Antimicrobial Dosing In Paediatric Cystic Fibrosis, Sahand Imani

Theses

Children with cystic fibrosis (CF) are predisposed to recurrent pulmonary exacerbations throughout their lifetime. This is characterised by an acute worsening of respiratory symptoms in the setting of bacterial infection and results in significant morbidity and mortality. Appropriate antimicrobial therapy is fundamental to management, in particular aminoglycoside antibiotics. Tobramycin is the preferred aminoglycoside of choice, usually administered intravenously for 7 to 14 days.

Tobramycin dosing can be challenging in patients with CF. This is due to the underlying pharmacokinetic derangements (e.g., volume of distribution, organ function) frequently observed in this population. Accordingly, the use of standard dosing (based on age …

Design And Synthesis Of Α-Anomeric Diacetylene-Containing Glycosides As Photopolymerizable Molecular Gelators, Guijun Wang, Dan Wang, Anji Chen, Ifeanyi S. Okafor, Lalith Palitha Samankumara

Chemistry & Biochemistry Faculty Publications

Glycolipids with diacetylene functional groups are fascinating compounds with many practical uses. Among these, diacetylene-containing gelators are especially important because they can form photopolymerizable gels, which are useful stimuli-responsive materials. Inspired by the unique properties of diacetylene-containing gelators and to understand the structural influences especially the location of the diacetylene functional groups on the self-assembling properties, a series of 15 novel N-acetyl-d-glucosamine derivatives with the diacetylene functional group introduced at the anomeric position were designed and synthesized. The diacetylene function is attached to the sugar through α-glycosylation with the distance from the anomeric oxygen being varied from one, two, …

Why Glucagon Matters For Hypoglycemia And Physical Activity In Individuals With Type 1 Diabetes, Sheri R. Colberg

Human Movement Sciences Faculty Publications

No abstract provided.

Epidemiology Of ∆8thc-Related Carcinogenesis In Usa: A Panel Regression And Causal Inferential Study, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

The use of ∆8THC is increasing at present across the USA in association with widespread cannabis legalization and the common notion that it is “legal weed”. As genotoxic actions have been described for many cannabinoids, we studied the cancer epidemiology of ∆8THC. Data on 34 cancer types was from the Centers for Disease Control Atlanta Georgia, substance abuse data from the Substance Abuse and Mental Health Services Administration, ethnicity and income data from the U.S. Census Bureau, and cannabinoid concentration data from the Drug Enforcement Agency, were combined and processed in R. Eight cancers (corpus uteri, liver, gastric cardia, breast …

Effects Of Cannabis On Congenital Limb Anomalies In 14 European Nations: A Geospatiotemporal And Causal Inferential Study, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

Cannabinoid exposure is increasing in some European nations. Europe therefore provides an interesting test environment for the recently reported link between cannabis exposure and congenital limb anomaly (CLA) rates (CLARs). Exponential genotoxic dose–response relationships make this investigation both intriguing and imperative. Annual CLAR in 14 nations were from Epidemiological Surveillance of Congenital Anomalies. Drug use rates were from European Monitoring Centre for Drugs and Drug Dependency. Median household income was from the World Bank. E-values provide a quantitative measure of robustness of results to confounding by extraneous covariates. Inverse probability weighting is an important technique for equalizing exposures across countries …

European Epidemiological Patterns Of Cannabis- And Substance-Related Congenital Cardiovascular Anomalies: Geospatiotemporal And Causal Inferential Study, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

As prenatal and community cannabis exposures have recently been linked with congenital heart disease (CHD), it was of interest to explore these associations in Europe in a causal framework and space-time context. Congenital anomaly data from Eurocat, drug-use data from the European Monitoring Centre for Drugs and Drug Addiction, and income from the World Bank. Countries with rising daily cannabis use had in general higher congenital anomaly rates over time than those without (time: status interaction: β-Est. = 0.0267, P = 0.0059). At inverse probability-weighted panel regression, cannabis terms were positive and significant for CHD, severe CHD, atrial septal defect, …

Itraconazole Nanocomposites Prepared Via Rotary Evaporator Drying Of Nanomilled Suspensions, Alexander Santos Coelho

Theses

The aim of this study is to explore the feasibility of rotary evaporation for drying wetmilled drug suspensions as a novel approach to produce drug nanocomposites that exhibit fast redispersion and immediate drug release. To this end, the physical stability of the nanomilled itraconazole (drug) suspensions, a.k.a., nanosuspensions, during the milling and storage; the drying of the itraconazole nanosuspensions via the rotary evaporator; and the type/loading of various polymers/surfactants (dispersants) on aqueous redispersion and drug release from the nanocomposites were examined. Our results suggest that smaller drug particle size, owing to nanomilling, and smaller nanocomposite particle size, owing to optimized …

The Benefits Of Astaxanthin To Improve Pain Relief In Patients With Painful Diabetic Neuropathy: An Open-Label, Randomized Controlled Trial, Rizaldy Taslim Pinzon, Mary Rose Angelina Budi Harsana

Pharmaceutical Sciences and Research

Treatment of diabetic neuropathy is still carried out by providing symptomatic therapy, which only improves ± 50% of the total symptoms felt by patients, but does not tackle the underlying causes of the disease. Astaxanthin is a potent antioxidant, anti-inflammatory, and anti-diabetic carotenoid that could be an additional treatment option. We aimed to measure the effectiveness of administering astaxanthin as an additional therapy to improve the impact of pain and discomfort experienced daily by diabetes mellitus patients with painful diabetic neuropathy. We conducted a randomized experimental study with an open label design of 36 patients who had been diagnosed with …

Biologic Tnf-Α Inhibitors Reduce Microgliosis, Neuronal Loss, And Tau Phosphorylation In A Transgenic Mouse Model Of Tauopathy, Weijun Ou, Joshua Yang, Juste Simanauskaite, Matthew Choi, Demi M. Castellanos, Rudy Chang, Jiahong Sun, Nataraj Jagadeesan, Karen D. Parfitt, David H. Cribbs, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background

Tumor necrosis factor-α (TNF-α) plays a central role in Alzheimer’s disease (AD) pathology, making biologic TNF-α inhibitors (TNFIs), including etanercept, viable therapeutics for AD. The protective effects of biologic TNFIs on AD hallmark pathology (Aβ deposition and tau pathology) have been demonstrated. However, the effects of biologic TNFIs on Aβ-independent tau pathology have not been reported. Existing biologic TNFIs do not cross the blood–brain barrier (BBB), therefore we engineered a BBB-penetrating biologic TNFI by fusing the extracellular domain of the type-II human TNF-α receptor (TNFR) to a transferrin receptor antibody (TfRMAb) that ferries the TNFR into the brain via …