Endocrine System Commons^™

Epigenetic Impact Of Endocrine Disrupting Chemicals On Lipid Homeostasis And Atherosclerosis: A Pregnane X Receptor-Centric View, Robert N. Helsley, Changcheng Zhou

Pharmacology and Nutritional Sciences Faculty Publications

Despite the major advances in developing diagnostic techniques and effective treatments, atherosclerotic cardiovascular disease (CVD) is still the leading cause of mortality and morbidity worldwide. While considerable progress has been achieved to identify gene variations and environmental factors that contribute to CVD, much less is known about the role of “gene–environment interactions” in predisposing individuals to CVD. Our chemical environment has significantly changed in the last few decades, and there are more than 100,000 synthetic chemicals in the market. Recent large-scale human population studies have associated exposure to certain chemicals including many endocrine disrupting chemicals (EDCs) with increased CVD risk, …

Measurement Of The Absolute Magnitude And Time Courses Of Mitochondrial Membrane Potential In Primary And Clonal Pancreatic Beta-Cells, Akos Gerencser, Shona A. Mookerjee, Martin Jastroch, Martin D. Brand

Faculty Publications & Research of the TUC College of Pharmacy

The aim of this study was to simplify, improve and validate quantitative measurement of the mitochondrial membrane potential (ΔψM) in pancreatic β-cells. This built on our previously introduced calculation of the absolute magnitude of ΔψM in intact cells, using time-lapse imaging of the non-quench mode fluorescence of tetramethylrhodamine methyl ester and a bis-oxonol plasma membrane potential (ΔψP) indicator. ΔψM is a central mediator of glucose-stimulated insulin secretion in pancreatic β-cells. ΔψM is at the crossroads of cellular energy production and demand, therefore precise assay of its magnitude is a valuable tool to study how these processes interplay in insulin secretion. …

Capillary Endothelia From Two Adpkd Patients Are Polyploidy, Sarmed H. Kathem, Wissam A. Aboualaiwi, Xiaolin Zi, Surya M. Nauli

Pharmacy Faculty Articles and Research

Bilateral renal cyst formation is the main feature of autosomal dominant polycystic kidney disease (ADPKD). We and other laboratories have previously shown that cystlining epithelia of kidneys from ADPKD patients are characterized by polyploidy. In this report, we show that endothelia from the renal capillary beds of two ADPKD patients are also polyploidy. Spectral karyotyping study further confirms our flow cytometry analyses. We suggest that polyploidy may be used as a potential cellular marker in ADPKD.

Posterior Approach To Kidney Dissection: An Old Surgical Approach For Integrated Medical Curricula, Frank J. Daly, David L. Bolender, Deepali Jain, Sheryl Uyeda, Todd M. Hoagland

Biomedical Sciences Faculty Publications

Integrated medical curricular changes are altering the historical regional anatomy approach to abdominal dissection. The renal system is linked physiologically and biochemically to the cardiovascular and respiratory systems, yet anatomist often approach the urinary system as part of the abdomen and pelvic regions. As part of an integrated curriculum, the renal system must be covered relatively quickly after the thorax in the cadaver lab, often without the opportunity to fully appreciate the rest of the abdominal contents. This paper provides dissection instructions that follow the one of the historical surgical approaches for nephrectomy, including preservation of the posterior abdominal wall …

Female Breakfast Skippers Display A Disrupted Cortisol Rhythm And Levated Blood Pressure, Megan Witbracht, Nancy L. Keim, Shavawn Forester, Adrianne Widaman, Kevin D. Laugero

United States Department of Agriculture-Agricultural Research Service / University of Nebraska-Lincoln: Faculty Publications

Chronic stress and over-activity in the hypothalamic–pituitary–adrenal (HPA) axis may link breakfast skipping and poor cardiometabolic health. Missing the first major meal of the day in rodents prolongs elevated circulating corticosterone at a time when it's normally decreasing. To extend these findings to humans, we hypothesized that habitual breakfast skippers would display a similar pattern of circulating cortisol and alterations in meal and stress-induced cortisol reactions. Normal weight to obese women aged 18–45 years old who were strictly defined as either breakfast skippers (n = 30) or breakfast eaters (n = 35) were invited to participate in our …

Empagliflozin In The Treatment Of Type 2 Diabetes: Evidence To Date, Jay H. Shubrook, Babak Baradar Bokaie, Sarah E. Adkins

Faculty Publications & Research of the TUC College of Osteopathic Medicine

In the last decade, researchers have gained a greater understanding of the pathophysiologic mechanisms of type 2 diabetes as a chronic and progressive disease. One of the more recent treatment targets is the kidney. The kidneys become maladaptive in diabetes by increasing the reabsorption of glucose above the normal physiologic renal threshold. This discovery has led to the development of the sodium/glucose cotransporter 2 inhibitors (SGLT2). These agents readjust the renal threshold for glucose reabsorption to a lower level and decrease glucose reabsorption, while increasing urinary glucose when the glucose is above the renal threshold and subsequently lowering plasma glucose. …

Dopaminergic Signaling Within The Primary Cilia In The Renovascular System, Kimberly F. Atkinson, Samred H. Kathem, Xingjian Jin, Brian S. Muntean, Wissam A. Aboualaiwi, Andromeda M. Nauli, Surya M. Nauli

Pharmacy Faculty Articles and Research

Activation of dopamine receptor type-5 (DR5) has been known to reduce systemic blood pressure, most likely by increasing renal vasodilation and enhancing natriuresis in the kidney. However, the mechanism of DR5 in natriuresis and vasodilation was not clearly known. We have previously shown that DR5 is localized to primary cilia of proximal renal epithelial and vascular endothelial cells. We here show that selective activation of DR5 specifically induces calcium influx only in the primary cilia, whereas non-selective activation of dopamine receptor induces calcium fluxes in both cilioplasm and cytoplasm. Cilia-independent signaling induced by thrombin only shows calcium signaling within cytoplasm. …

Roles Of Dopamine Receptor On Chemosensory And Mechanosensory Primary Cilia In Renal Epithelial Cells, Viralkumar S. Upadhyay, Brian S. Muntean, Samred H. Kathem, Jangyoun J. Hwang, Wissam A. Aboualaiwi, Surya M. Nauli

Pharmacy Faculty Articles and Research

Dopamine plays a number of important physiological roles. However, activation of dopamine receptor type-5 (DR5) and its effect in renal epithelial cells have not been studied. Here, we show for the first time that DR5 is localized to primary cilia of LLCPK kidney cells. Renal epithelial cilia are mechanosensory organelles that sense and respond to tubular fluid-flow in the kidney. To determine the roles of DR5 and sensory cilia, we used dopamine to non-selectively and fenoldopam to selectively activate ciliary DR5. Compared to mock treatment, dopamine treated cells significantly increases the length of cilia. Fenoldopam further increases the length of …

Variceal Bleeding From Cirrhosis: A Clinical Review Of Causes And Pharmacotherapy Options, Hillary Aphaisuwan, Ibrahim Lala, Laura Tsu

Pharmacy Faculty Articles and Research

This home-study CPE activity has been developed to educate pharmacists on the prevention and treatment of hemorrhagic esophageal varices resulting from cirrhosis.

The Roles Of Primary Cilia In Polycystic Kidney Disease, Samred H. Kathem, Ashraf M. Mohieldin, Surya M. Nauli

Pharmacy Faculty Articles and Research

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited genetic disorder that results in progressive renal cyst formation with ultimate loss of renal function and other systemic disorders. These systemic disorders include abnormalities in cardiovascular, portal, pancreatic and gastrointestinal systems. ADPKD is considered to be among the ciliopathy diseases due to the association with abnormal primary cilia function. In order to understand the full course of primary cilia and its association with ADPKD, the structure, functions and role of primary cilia have been meticulously investigated. As a result, the focus on primary cilia has emerged to support the vital roles …

Mice Deficient In Gem Gtpase Show Abnormal Glucose Homeostasis Due To Defects In Beta-Cell Calcium Handling, Jenny E. Gunton, Mary Sisavanh, Rebecca A. Stokes, Jon Satin, Leslie S. Satin, Min Zhang, Sue M. Liu, Weikang Cai, Kim Cheng, Gregory J. Cooney, D. Ross Laybutt, Trina So, Juan-Carlos Molero, Shane T. Grey, Douglas A. Andres, Michael S. Rolph, Charles R. Mackay

Physiology Faculty Publications

AIMS AND HYPOTHESIS: Glucose-stimulated insulin secretion from beta-cells is a tightly regulated process that requires calcium flux to trigger exocytosis of insulin-containing vesicles. Regulation of calcium handling in beta-cells remains incompletely understood. Gem, a member of the RGK (Rad/Gem/Kir) family regulates calcium channel handling in other cell types, and Gem over-expression inhibits insulin release in insulin-secreting Min6 cells. The aim of this study was to explore the role of Gem in insulin secretion. We hypothesised that Gem may regulate insulin secretion and thus affect glucose tolerance in vivo.

METHODS: Gem-deficient mice were generated and their metabolic phenotype characterised by in …

Endocrine Complications In Patients Of Beta Thalassemia Major In A Tertiary Care Hospital In Pakistan, Amina Adil, Zain A. Sobani, Abdul Jabbar, Salman N Adil, Safia Awan

Section of Diabetes, Endocrinology and Metabolism

OBJECTIVE: To determine the major endocrine complications present in patients of Thalassemia major presenting to a tertiary care center in Karachi, Pakistan.

METHODS: Records of all thallasemia major patients at a Haematology Department in a tertiary care hospital of Karachi were retrospectively reviewed from May to August 2009 with specific focus on endocrine data and investigations. The patients' data was recorded in a questionnaire and analyzed using SPSS v.17, frequencies and percentages along with corresponding 95% confidence interval were computed.

RESULTS: Our data revealed that a significantly small percentage of those under care received regular endocrine follow-up. Male hypo-gonadal abnormalities …

Primary Cilia Regulates The Directional Migration And Barrier Integrity Of Endothelial Cells Through The Modulation Of Hsp27 Dependent Actin Cytoskeletal Organization, Thomas J. Jones, Ravi K. Adapala, Werner J. Geldenhuys, Chris Bursley, Wissam A. Aboualaiwi, Surya M. Nauli, Charles K. Thodeti

Pharmacy Faculty Articles and Research

Cilia are mechanosensing organelles that communicate extracellular signals into intracellular responses. Altered functions of primary cilia play a key role in the development of various diseases including polycystic kidney disease. Here, we show that endothelial cells from the oak ridge polycystic kidney (Tg737orpk/orpk) mouse, with impaired cilia assembly, exhibit a reduction in the actin stress fibers and focal adhesions compared to wild type. In contrast, endothelial cells from polycystin-1 deficient mice (pkd1null/null), with impaired cilia function, display robust stress fibers and focal adhesion assembly. We found that the Tg737orpk/orpk cells exhibit impaired directional migration and endothelial cell monolayer permeability compared …

Post Gastric Bypass Hypoglycemia: Four Cases Treated Successfully With Alphaglucosidase Inhibitor Therapy, Shavon S. Frankhouser Do, Aakif N. Ahmad Do, Gretchen A. Perilli Md, Benjamin J. Quintana Md, Marc A. Vengrove Do, Facp

Department of Medicine

No abstract provided.

The Effects Of 17Α-Ethynylestradiol (Ee2) On Gonadal Development And Differentiation In The Estuarine Killifish, Fundulus Heteroclitus, Ibrahim Chehade

Theses and Dissertations (Comprehensive)

Endocrine disrupting substances (EDSs) comprise a wide variety of chemicals that perturb normal endocrine function including developmental and reproductive processes in vertebrates. The synthetic estrogen 17α-ethynylestradiol (EE₂) is a commonly-used model EDS because of its environmental relevance and its effects on the reproductive endocrine system. Early life-stage exposure of fish to estrogenic EDSs causes effects such as intersex (ovotestes in males) and feminization. This study aims to confirm the period of gonadal differentiation in the estuarine killifish or mummichog (Fundulus heteroclitus) and to determine the sensitivity of gonadal development to EE₂. Artificially-regressed mummichog were spawned, and …

An Analysis Of Quality Outcomes In Patients Having A Hysterectomy: Robotics Vs The Vaginal Approach, Martin A. Martino Md, Jocelyn Shubella, Elizabeth A. Berger Do

Department of Obstetrics & Gynecology

No abstract provided.

Robotic Surgery Outcomes After The Learning Curve: Does Robotic Surgery Improve The Quality Health Outcome “Readmission <30 Days” In Patients Having Hysterectomy For Benign Disease?, Elizabeth A. Berger Do, Jocelyn Shubella, Martin A. Martino Md

Department of Obstetrics & Gynecology

No abstract provided.

Ethnic Disparity In 21-Hydroxylase Gene Mutations Identified In Pakistani Congenital Adrenal Hyperplasia Patient, Aysha Habib Khan, Muniba Aban, Jamal Raza, Naeem Ul Haq, Abdul Jabbar, Tariq Moatter

Department of Pathology and Laboratory Medicine

Background: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders caused by defects in the steroid 21 hydroxylase gene (CYP21A2). We studied the spectrum of mutations in CYP21A2 gene in a multi-ethnic population in Pakistan to explore the genetics of CAH.

Methods: A cross sectional study was conducted for the identification of mutations CYP21A2 and their phenotypic associations in CAH using ARMS-PCR assay.

Results: Overall, 29 patients were analyzed for nine different mutations. The group consisted of two major forms of CAH including 17 salt wasters and 12 simple virilizers. There were 14 phenotypic males and 15 females …

Editorial Focus: An Ace Inhibitor Improves Vascular Outcomes In A Pkd Model, Surya M. Nauli

Pharmacy Faculty Articles and Research

Cardiovascular complications are the most common cause of death in patients with polycystic kidney disease (PKD). Within the context of clinical practice, two possible theories have been reviewed that could help describe the pathogenesis of vascular complications in PKD (7).

Calcium-Mediated Mechanisms Of Cystic Expansion, Shakila Abdul-Majeed, Surya M. Nauli

Pharmacy Faculty Articles and Research

In this review, we will discuss several well-accepted signaling pathways toward calcium-mediated mechanisms of cystic expansion. The second messenger calcium ion has contributed to a vast diversity of signal transduction pathways. We will dissect calcium signaling as a possible mechanism that contributes to renal cyst formation. Because cytosolic calcium also regulates an array of signaling pathways, we will first discuss cilia-induced calcium fluxes, followed by Wnt signaling that has attributed to much-discussed planar cell polarity. We will then look at the relationship between cytosolic calcium and cAMP as one of the most important aspects of cyst progression. The signaling of …