Endocrine System Diseases Commons^™

Mir-30a Targets Gene Networks That Promote Browning Of Human And Mouse Adipocytes, Pradip K Saha, Mark P Hamilton, Kimal Rajapakshe, Vasanta Putluri, Jessica B Felix, Peter Masschelin, Aaron R Cox, Mandeep Bajaj, Nagireddy Putluri, Cristian Coarfa, Sean M Hartig

Faculty, Staff and Students Publications

MicroRNA-30a (miR-30a) impacts adipocyte function, and its expression in white adipose tissue (WAT) correlates with insulin sensitivity in obesity. Bioinformatic analysis demonstrates that miR-30a expression contributes to 2% of all miRNA expression in human tissues. However, molecular mechanisms of miR-30a function in fat cells remain unclear. Here, we expanded our understanding of how miR-30a expression contributes to antidiabetic peroxisome proliferator-activated receptor-γ (PPARγ) agonist activity and metabolic functions in adipocytes. We found that WAT isolated from diabetic patients shows reduced miR-30a levels and diminished expression of the canonical PPARγ target genes ADIPOQ and FABP4 relative to lean counterparts. In human adipocytes, …

Metformin Enhances Autophagy And Normalizes Mitochondrial Function To Alleviate Aging-Associated Inflammation, Leena P Bharath, Madhur Agrawal, Grace Mccambridge, Dequina A Nicholas, Hatice Hasturk, Jing Liu, Kai Jiang, Rui Liu, Zhenheng Guo, Jude Deeney, Caroline M Apovian, Jennifer Snyder-Cappione, Gregory S Hawk, Rebecca M Fleeman, Riley M F Pihl, Katherine Thompson, Anna C Belkina, Licong Cui, Elizabeth A Proctor, Philip A Kern, Barbara S Nikolajczyk

Faculty, Staff and Student Publications

Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and bioinformatic analyses showed that Th17 cytokine production differentiates CD4+ T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and improving mitochondrial bioenergetics. By contrast, autophagy-targeting siRNA disrupted redox balance in T cells from young subjects and activated the Th17 …

Glycemic Control And Infections Among Us Hemodialysis Patients With Diabetes Mellitus, Jinnie J Rhee, Yuanchao Zheng, Sai Liu, Maria E Montez-Rath, Richard J Hamill, Julie H Ishida, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

INTRODUCTION: Patients with diabetes mellitus (DM) on hemodialysis (HD) may be particularly vulnerable to infections.

METHODS: We used merged data from the United States Renal Data System and electronic health records data from a large US dialysis provider to retrospectively examine the association between glycemic control and infections in these patients. Adult patients with DM aged ≥18 years who initiated in-center maintenance HD treatment from 2006 to 2011 and survived >90 days were included. Quarterly mean time-averaged hemoglobin A1c (HbA1c) values were categorized into

RESULTS: In a cohort of 33,753 eligible patients, those with higher HbA1c levels had higher rates …

Myeloma Cells Shift Osteoblastogenesis To Adipogenesis By Inhibiting The Ubiquitin Ligase Murf1 In Mesenchymal Stem Cells, Zhiqiang Liu, Huan Liu, Jin He, Pei Lin, Qiang Tong, Jing Yang

Faculty, Staff and Students Publications

The suppression of bone formation is a hallmark of multiple myeloma. Myeloma cells inhibit osteoblastogenesis from mesenchymal stem cells (MSCs), which can also differentiate into adipocytes. We investigated myeloma-MSC interactions and the effects of such interactions on the differentiation of MSCs into adipocytes or osteoblasts using single-cell RNA sequencing, in vitro co-culture, and subcutaneous injection of MSCs and myeloma cells into mice. Our results revealed that the α4 subunit of integrin on myeloma cells stimulated vascular cell adhesion molecule 1 (VCAM1) on MSCs, leading to the activation of protein kinase C β1 (PKCβ1) signaling and repression of the muscle ring-finger …

An Investigation Of Treatments For The Prevention Of Metabolic Complications For Women Suffering From Polycystic Ovarian Syndrome: Diet, Exercise, Weight Reduction And Herbal Remedies, Brenda Martinez-Puente

Nursing | Senior Theses

The purpose of this research study is to compare the views of traditional versus alternative treatments available to women with Polycystic Ovarian Syndrome (PCOS) suffering from metabolic complications. Alternative treatments include diet, exercise, herbal remedies, or any combination of the three. Pharmacological interventions for the conditions associated with PCOS such as metformin, used to control glucose levels, and clomiphene, used to treat infertility. Through the literature review, articles show herbs and plant products to have similar mechanisms of actions as the pharmacological interventions, but with less side effects. For example, cinnamon was shown to increase insulin sensitivity and pomegranate juice …

Metabolic-Sensing Of The Skeletal Muscle Clock Coordinates Fuel Oxidation, Hongshan Yin, Weini Li, Somik Chatterjee, Xuekai Xiong, Pradip Saha, Vijay Yechoor, Ke Ma

Faculty, Staff and Students Publications

Circadian clock confers temporal control in metabolism, with its disruption leading to the development of insulin resistance. Metabolic substrate utilization in skeletal muscle is coordinated with diurnal nutrient cycles. However, whether the molecular clock is involved in this coordination is largely unknown. Using a myocyte-selective genetic ablation mouse model of the essential clock activator Bmal1, here we identify muscle-intrinsic clock as a sensor of feeding cues to orchestrate skeletal muscle oxidation required for global nutrient flux. Bmal1 in skeletal muscle responds robustly to feeding in vivo and insulin induces its expression. Muscle Bmal1 deficiency impaired the transcriptional control of glucose …

Giving Credence To The Experience Of X-Linked Hypophosphatemia In Adulthood: An Interprofessional Mixed-Methods Study, Melissa Hughes, Carolyn Macica, Catherine Meriano, Maya Doyle

Journal of Patient-Centered Research and Reviews

Purpose: X-linked hypophosphatemia (XLH) is a rare X-linked dominant metabolic bone disease, often diagnosed in childhood but causing increasing physical debilitation and pain in adulthood. Physical comorbidities of XLH in adulthood include pervasive and early-onset degenerative arthritis, mineralizing enthesophytes and osteophytes, osteomalacia and pseudofracture, dental abscesses, and hearing loss.

Methods: This mixed-methods analysis included physical findings, diagnostic imaging, occupational and physical therapy assessments, and semi-structured interviews by social work to understand the functional outcomes and lived experience of XLH in adulthood, through connections between qualitative data obtained by social work and occupational therapy with the quantitative findings from other disciplines. …

Association Of Intensive Lifestyle Intervention, Fitness, And Body Mass Index With Risk Of Heart Failure In Overweight Or Obese Adults With Type 2 Diabetes Mellitus: An Analysis From The Look Ahead Trial, Ambarish Pandey, Kershaw V Patel, Judy L Bahnson, Sarah A Gaussoin, Corby K Martin, Ashok Balasubramanyam, Karen C Johnson, Darren K Mcguire, Alain G Bertoni, Dalane Kitzman, Jarett D Berry, Look Ahead Research Group

Faculty, Staff and Students Publications

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with a higher risk for heart failure (HF). The impact of a lifestyle intervention and changes in cardiorespiratory fitness (CRF) and body mass index on risk for HF is not well established.

METHODS: Participants from the Look AHEAD trial (Action for Health in Diabetes) without prevalent HF were included. Time-to-event analyses were used to compare the risk of incident HF between the intensive lifestyle intervention and diabetes support and education groups. The associations of baseline measures of CRF estimated from a maximal treadmill test, body mass index, and longitudinal changes in these …

Diabetes Debunked: What You Need To Know, Maggie Hutson

Honors Program: Senior Projects (Public)

The goal of this Honors creative project is to encourage health literacy in populations who are curious about Type 2 Diabetes or have Type 2 Diabetes. From personal experience, I have seen noncompliance in diabetics and wondered why since it is a serious, progressive disease. After researching, I found that some diabetics do not understand the scope of their disease, especially since many of the dangerous complications that arise from Type 2 Diabetes do not present until later in the disease when it is too late. For my senior project, I decided to write an educational paper as a supplement …

The Impact Of Diabetic Foot Ulcers And Unilateral Offloading Footwear On Gait In People With Diabetes, Erica Ling, Brian Lepow, He Zhou, Ana Enriquez, Ashley Mullen, Bijan Najafi

Faculty, Staff and Students Publications

BACKGROUND: Unilateral offloading footwear prescribed to patients with diabetic foot ulcers elevates one limb relative to the other, which may lead to limp and abnormal gait. This study investigated whether the unilateral foot ulcer and offloading combination negatively impacts gait function beyond diabetic peripheral neuropathy.

METHODS: Eighty-six participants were recruited in 3 groups: 12 with diabetic peripheral neuropathy and unilateral foot ulcers wearing offloading footwear (offloading group, age = 55.6 ± 9.5 years, BMI = 30.9 ± 4.5 kg/m

FINDINGS: The offloading group exhibited deteriorated gait function compared to the non-diabetic group (p < 0.005, Cohen's effect size d = 0.90-2.61). They also had decreased gait speed (p < 0.001, d = 1.79) and stride length (p < 0.001, d = 1.76), as well as increased gait cycle time (p < 0.001, d = 1.67) and limp (p < 0.050, d = 0.72-1.49) compared to the neuropathy group. The offloading group showed increased gait unsteadiness compared to the neuropathy group, but the difference did not reach statistical significance in our samples.

INTERPRETATION: This study demonstrated that while diabetic …

Metabolic Dysregulation In The Atp7b-/- Wilson's Disease Mouse Model, Clavia Ruth Wooton-Kee, Matthew Robertson, Ying Zhou, Bingning Dong, Zhen Sun, Kang Ho Kim, Hailan Liu, Yong Xu, Nagireddy Putluri, Pradip Saha, Cristian Coarfa, David D Moore, Alli M Nuotio-Antar

Faculty, Staff and Students Publications

Inactivating mutations in the copper transporter Atp7b result in Wilson’s disease. The Atp7b−/− mouse develops hallmarks of Wilson’s disease. The activity of several nuclear receptors decreased in Atp7b−/− mice, and nuclear receptors are critical for maintaining metabolic homeostasis. Therefore, we anticipated that Atp7b−/− mice would exhibit altered progression of diet-induced obesity, fatty liver, and insulin resistance. Following 10 wk on a chow or Western-type diet (40% kcal fat), parameters of glucose and lipid homeostasis were measured. Hepatic metabolites were measured by liquid chromatography–mass spectrometry and correlated with transcriptomic data. Atp7b−/− mice fed a chow diet presented …

Aromatase Inhibitors Plus Weight Loss Improves The Hormonal Profile Of Obese Hypogonadal Men Without Causing Major Side Effects, Georgia Colleluori, Rui Chen, Christie G Turin, Francesca Vigevano, Clifford Qualls, Biju Johnson, Sanjay Mediwala, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

Objective: In obese men, the increased expression of the aromatase enzyme in adipose tissue leads to high conversion of androgens to estrogens contributing to hypogonadotropic hypogonadism (HHG). Our objective is to evaluate efficacy and safety of weight loss (WL) plus aromatase inhibitor (AI) therapy in severely obese men with HHG. We hypothesize that AI+WL will be more effective as compared to WL alone in improving the hormonal profile, thus muscle strength and symptoms of HHG (primary outcomes), with no significant adverse effects on lean mass, metabolic profile, and bone mineral density (secondary outcomes).

Design: Randomized double-blind placebo-controlled pilot trial.

Methods: …

A Remarkable Response Of Granulomatous Hypophysitis To Infliximab In A Patient With A Background Of Crohn's Disease-A Case Report, Bahar K Force, Tiphanie P Vogel, Dang M Nguyen, Kent A Heck, Sherly Sebastian, Mas Takashima, Daniel Yoshor, Susan L Samson

Faculty, Staff and Students Publications

Associated Data

Hypogonadism, Type-2 Diabetes Mellitus, And Bone Health: A Narrative Review, Vittoria Russo, Rui Chen, Reina Armamento-Villareal

Faculty, Staff and Students Publications

One of the complications from chronic hyperglycemia and insulin resistance due to type 2 diabetes mellitus (T2DM) on the hypothalamic-pituitary-gonadal axis in men is the high prevalence of hypogonadotropic hypogonadism (HH). Both T2DM and hypogonadism are associated with impaired bone health and increased fracture risk but whether the combination results in even worse bone disease than either one alone is not well-studied. It is possible that having both conditions predisposes men to an even greater risk for fracture than either one alone. Given the common occurrence of HH or hypogonadism in general in T2DM, a significant number of men could …

Sirt3 Promotes Lipophagy And Chaperon-Mediated Autophagy To Protect Hepatocytes Against Lipotoxicity, Tian Zhang, Jingxin Liu, Shengnan Shen, Qiang Tong, Xiaojun Ma, Ligen Lin

Faculty, Staff and Students Publications

Lipophagy is a lysosomal lipolytic pathway that complements the actions of cytosolic neutral lipases. Chaperon-mediated autophagy (CMA) triggers lipid droplets (LDs) breakdown, to initiate lipolysis via either cytosolic lipases or macroautophagy. SIRT3, a mitochondrial NAD+-dependent deacetylase, regulates the acetylation status and activity of many substrates involving in energy metabolism. However, the role of SIRT3 in regulating lipophagy is controversial. The current study showed that SIRT3 expression was decreased and the macroautophagy flux was blocked in the primary hepatocytes from high-fat diet fed mice and P/O (palmitic acid and oleic acid mixture) treated AML12 mouse hepatocytes, compared with the corresponding controls. …

The Acute Effect Of Water Intake On Glucose Regulation In Low Drinkers, Adam David Seal

Graduate Theses and Dissertations

Previous evidence suggests the hormone arginine vasopressin (AVP) may be a modifiable factor contributing to hyperglycemia. Significant differences in urine concentration and copeptin, a marker for AVP, have been observed between low and high water drinkers. Purpose: The purpose was to investigate the acute effect of adequate water intake on glucose regulation in low drinkers. Methods: 7 healthy (5 males, 2 female) low drinkers were recruited using a water frequency questionnaire (WFQ), spot and 24-h urine sample (age 43±6 y, BMI 30.9±3, WFQ volume 823±403 mL∙d-1, 24 h Uosm 961±105 mmol∙kg-1, copeptin 8.17±3.05 pmol∙L-1). During two experimental protocols, participants remained …

Prevention And Treatment Of Glucocorticoid-Induced Osteoporosis, Mackenzie Devine, Anh Dao Le, Julie Puvogel, Victoria Cho, Michelle Musser

Pharmacy and Wellness Review

Osteoporosis is a disease state resulting in decreased bone mineral density (BMD) and increased risk of fracture, specifically of the vertebrae, spine and hip. Risk factors and high risk populations for developing osteoporosis include low BMD, long-term glucocorticoid therapy, genetics, diet, postmenopausal women and patients with inflammatory or chronic disease states. A variety of signaling pathways involving hormones, cytokines and other signaling molecules are involved in bone formation and are affected by long-term glucocorticoid therapy, leading to the development of glucocorticoid-induced osteoporosis (GIO).

There are a variety of drugs that work efficaciously to prevent and treat GIO. Alendronate is a …

Potential Use Of Dopamine And Dopamine Agonists As Angiogenesis Inhibitors In The Treatment Of Cancer, Benjamin Finley, Katherine Liu, Daniel Powell, Jamie Kellner, David H. Kinder

Pharmacy and Wellness Review

In recent years, there have been numerous developments in monoclonal antibodies used as anticancer drugs with a focus on reducing the ability of cancers to metastasize and produce new vasculature. These agents are called angiogenesis inhibitors and although these agents have been proven effective in treating certain types of cancers, production and administration of monoclonal antibodies comes at a steep cost with a severe side effect profile. Under normal physiologic conditions, angiogenesis is an important mechanism to create new blood vessels from preexisting vessels, usually occurring in adults. Tumor cells can hijack the angiogenesis pathway to produce new distant tumors …

Improving Maternal And Fetal Health: A Look At Thyroid Function During Pregnancy, Sarah Ginty, Jessica Beck, Taylor Gauthier, Amanda Meyer, Michelle R. Musser

Pharmacy and Wellness Review

Maintenance of thyroid function during pregnancy is critical for both maternal and fetal health and development; therefore, knowledge regarding the relationship between thyroid hormones and pregnancy is essential. The American Thyroid Association task force has developed clinical guidelines on the diagnosis and treatment of thyroid disease during pregnancy. Gestational thyroid diseases are divided into two classifications, hypothyroidism and hyperthyroidism, which are further divided into more specific classifications based on clinical presentation. Differentiation, diagnosis, and monitoring of thyroid diseases throughout pregnancy require assessing symptoms, as well as obtaining levels of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) concentration by a simple …

Rising Rural Body-Mass Index Is The Main Driver Of The Global Obesity Epidemic In Adults, Con Burns, Tara Coppinger, Janette Walton, Et Al

Publications

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities1,2. This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity3,4,5,6. Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to …

Environmental Regulation Of The Heart: The Role Of Non-Coding Rna And Epigenetics In Influencing Mitochondrial And Cellular Health, Quincy Alexander Hathaway

Graduate Theses, Dissertations, and Problem Reports (ETD)

The mitochondrion, a small but ubiquitously distributed organelle in the cell, continues to be the focus of many disease pathogeneses, tissue and organ dysfunctions, and other morbidities that occur throughout the body. The purpose of this work was to understand how cardiac mitochondrion are altered in disease and pathological states, specifically in their adaptation to environmentally stimulated regulatory networks, such as epigenetic modifications and promotion/inhibition of non-coding RNAs. Acute stress to mitochondrial regulation (inhalation toxicology) as well as chronic (type 2 diabetes mellitus) was examined. Using a FVB transgenic microRNA-378a mouse knockout model, the cardiovascular impact derived from altering the …

Efficacy And Renal Outcomes Of Sglt2 Inhibitors In Patients With Type 2 Diabetes And Chronic Kidney Disease, Michael S. Kelly, Jelena Lewis, Ashley M. Huntsberry, Lauren Dea, Ivan Portillo

Pharmacy Faculty Articles and Research

Objective: To review glucose-lowering efficacy and changes in renal function associated with sodium-glucose co-transporter 2 (SGLT2) inhibitors among patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM).

Data sources: A literature search of MEDLINE and Cochrane databases was performed from 2000 to August 2018 using search terms: SGLT2 inhibitors, sodium glucose co-transporter 2, canagliflozin, empagliflozin, dapagliflozin, ertugliflozin, and chronic kidney disease. References of identified articles were also reviewed.

Study selection and data extraction: English-language studies investigating glucose-lowering endpoints and/or changes in renal function with one of four U.S. approved SGLT2 inhibitors were included. A …

Stem Cell Generated Β-Cells: A Possible Solution To The Growing Problem Of Type 1 Diabetes, Danielle Rae Steffen

Biology: Student Scholarship & Creative Works

Type 1 diabetes is a growing problem throughout the world. At this time, there is no functional cure, only various treatment options. However, in recent years there has been a significant increase in both the quantity and quality of research into potential cures for type 1 diabetes. This has led to a variety of new possibilities, the most promising of which are β-cells generated from the patient’s own stem cells.

Loss Of Marv1 Promotes Chop Signaling In Mouse Liver, Shad Anthony Mitchell

Graduate School of Biomedical Sciences Theses and Dissertations

Metabolic syndrome (MetS) is a term used to define a set of metabolic diseases: obesity, type 2 diabetes (T2D), hyperlipidemia, hypertension, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic hepatosteatosis (NASH). Those with MetS have a higher incidence of cardiovascular disease and stroke. Current drug treatments for MetS treat the individual pathologies associated with the diseases, rather than directly targeting MetS as a whole. We hypothesize that the inhibition of a ubiquitous lipid transporter known as ARV1 can improve pathologies associated with MetS. To test this hypothesis, we utilized liver tissue from mARV1 knockout mice fed a high-fat diet and examined …

Gene Regulation In The Hypothalamic-Pituitary-Gonadal Axis Of The Green Anole Lizard (Anolis Carolinensis)., Joshua N. Peters

All Graduate Theses, Dissertations, and Other Capstone Projects

Studies examining the hypothalamic-pituitary-gonad axis (HPG) in Anolis carolinensis provide insight into the regulation of this axis under extremely different reproductive conditions. Molecular studies indicate that kisspeptin proteins, transcribed from kiss1 and kiss2 genes, are produced in the hypothalamus where they bind G protein-coupled receptor 54 (GPR54), activating the HPG axis. Gonadotropin inhibitory hormone (GnIH) and its receptors, G protein-coupled receptor 147 and 74 (GPR147 and GPR74), down regulate HPG axis function. In this experiment we examined HPG axis gene expression in the green anole lizard (Anolis carolinensis), a seasonally breeding species with higher steroid hormone levels in the breeding …

Comparative Effectiveness And Safety Of Empagliflozin On Cardiovascular Mortality And Morbidity In Adults With Type 2 Diabetes, Wilbert S. Aronow, Tatyana Shamliyan

NYMC Faculty Publications

Background: Based on a single placebo-controlled randomized clinical trial, empagliflozin is licensed to reduce cardiovascular death in diabetes and comorbid cardiovascular disease. Methods: We examined the comparative effectiveness of empagliflozin on mortality and cardiovascular morbidity in type 2 diabetes. We conducted random-effects direct frequentist meta-analyses of aggregate data and appraised the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Our search in PubMed, EMBASE, the Cochrane Library, clinicaltrials.gov, and PharmaPendium up to May 2017 identified 11 meta-analyses, multiple publications, and unpublished data from 29 randomized controlled trials (RCTs). Results: Empagliflozin reduces all-cause mortality [relative …

Temporal Changes In Cortical And Hippocampal Expression Of Genes Important For Brain Glucose Metabolism Following Controlled Cortical Impact Injury In Mice, June Zhou, Mark Burns, Linda Huynh, Sonia Villapol, Daniel D. Taub, Juan M. Saavedra, Marc R. Blackman

Pharmacology and Physiology Faculty Publications

Traumatic brain injury (TBI) causes transient increases and subsequent decreases in brain glucose utilization. The underlying molecular pathways are orchestrated processes and poorly understood. In the current study, we determined temporal changes in cortical and hippocampal expression of genes important for brain glucose/lactate metabolism and the effect of a known neuroprotective drug telmisartan on the expression of these genes after experimental TBI. Adult male C57BL/6J mice (n = 6/group) underwent sham or unilateral controlled cortical impact (CCI) injury. Their ipsilateral and contralateral cortex and hippocampus were collected 6 h, 1, 3, 7, 14, 21, and 28 days after injury. …

A Functional Algorithm For Weight Loss And Obesity Practice: Guide For Clinical Decision-Making For Treating Women, Jennifer A. Tice Williams

Dissertations

ABSTRACT

Background

Overweight and obesity have significant impact and consequences on women leading to reduced quality of life, comorbid conditions and premature mortality. Many healthcare providers lack adequate training and the time to properly treat overweight and obesity. Algorithms have been shown to improve clinical knowledge and save time.

Objectives

To develop an algorithm for weight loss assessment and treatment to aid in the clinical decision-making process while improving the quality of care for overweight and obese clients in an efficient manner that can be replicated.

Methods

After an extensive literature review to identify best-practice guidelines for weight loss a …

Impact Of Cyp2d6 Genotype On Amitriptyline Efficacy For The Treatment Of Diabetic Peripheral Neuropathy: A Pilot Study., Mamoonah Chaudhry, Marco Alessandrini, Jacobus Rademan, Tyren M. Dodgen, Francois E. Steffens, Danie G. Van Zyl, Andrea Gaedigk, Michael S. Pepper

Manuscripts, Articles, Book Chapters and Other Papers

AIM: Therapy with low-dose amitriptyline is commonly used to treat painful diabetic peripheral neuropathy. There is a knowledge gap, however, regarding the role of variable CYP2D6-mediated drug metabolism and side effects (SEs). We aimed to generate pilot data to demonstrate that SEs are more frequent in patients with variant CYP2D6 alleles.

METHOD: To that end, 31 randomly recruited participants were treated with low-dose amitriptyline for painful diabetic peripheral neuropathy and their CYP2D6 gene sequenced.

RESULTS: Patients with predicted normal or ultra-rapid metabolizer phenotypes presented with less SEs compared with individuals with decreased CYP2D6 activity.

CONCLUSION: Hence, CYP2D6 genotype contributes to …

Biomarkers Of Sepsis: A Retrospective Approach, Jose M. Roberts

Williams Honors College, Honors Research Projects

Background: Biomarkers are taking the spotlight in becoming the norm for early diagnoses. Sepsis is an inflammatory disease that increases metabolic rate in children. The first biomarker is hyponatremia. Hyponatremia is a frequent electrolyte imbalance in clinical practice, often observed in children with inflammatory disease and infection. Presence of hyponatremia is associated with electrical signaling imbalances, inflammation and renal dysfunction. The clinical value of hyponatremia in pediatric patients is unknown. The C-reactive protein is a second biomarker. Its presence signifies that necrotic cells and inflammation are present.

Objectives: To evaluate the use of biomarkers in children seen in the Emergency …