Digital Commons Network^™

Different Types Of Housing And Respiratory Health Outcomes, Wen Qi Gan, Wayne T. Sanderson, Steven R. Browning, David M. Mannino

Preventive Medicine and Environmental Health Faculty Publications

Evidence has shown that housing conditions may substantially influence the health of residents. Different types of housing have different structures and construction materials, which may affect indoor environment and housing conditions. This study aimed to investigate whether people living in different types of housing have different respiratory health outcomes. The data from the 1999–2006 National Health and Nutrition Examination Survey were used for the analyses. The types of housing included houses, townhouses, apartments, and mobile homes. Respiratory symptoms included wheezing, coughing, sputum, and dyspnea; respiratory diseases included asthma, chronic bronchitis, emphysema, and chronic obstructive pulmonary disease (COPD). Multiple logistic regression …

Control Of Hypertension Among Diabetic Patients In A Referral Hospital In Tanzania: A Cross-Sectional Study, Semvua B. Kilonzo, Daniel W. Gunda, Fatma Bakshi, Fredrick Kalokola, Henry A. Mayala, Hollo Dadi

Internal Medicine, East Africa

BACKGROUND: Hypertension is common among diabetic patients. The co-existence of two conditions carries an excessive risk of severe complications and mortalities. Limited information exists on the determinants of poor hypertension control among these patients. We aimed at determining the prevalence and factors associated with poor hypertension control in these patients.

METHODS: Data of diabetic patients who were also hypertensive attending an outpatient clinic from 1 August 2015 to 31 December 2015 at Bugando Medical Centre were retrospectively analyzed. Uncontrolled hypertension was defined as a blood pressure of ≥130mmHg and/or ≥80mmHg systolic and diastolic respectively. A designed questionnaire was used to …

Incidence, Risks, And Types Of Infections In Pediatric Long-Term Care Facilities, Lisa Saiman, Philip Maykowski, Meghan Murray, Bevin Cohen, Natalie Neu, Gordon R. Hutcheon, Elaine Larson

NYMC Faculty Publications

Importance: The population of infants, children, and adolescents cared for at pediatric long-term care facilities is increasing in complexity and size and thus consumes substantial health care resources. Infections are a significant cause of morbidity and mortality in this population, but few recent data describe their incidence and effects.

Objectives: To describe the types of infections diagnosed in residents of pediatric long-term care facilities, calculate infection rates, and identify risk factors for respiratory tract infections (RTIs).

Design, Setting, and Participants: This prospective cohort study, which was part of a larger trial called Keep It Clean for Kids, was conducted from …

Bronchoscopic Management Of Prolonged Air Leak, S Keshishyan, A Revelo, Oleg Epelbaum

NYMC Faculty Publications

Bronchopleural fistula (BPF) with prolonged air leak (PAL) is most often, though not always, a sequela of lung resection. When this complication occurs post-operatively, it is associated with substantial morbidity and mortality. Surgical closure of the defect is considered the definitive approach to controlling the source of the leak, but many patients with this condition are suboptimal operative candidates. Therefore there has been active interest for decades in the development of effective endoscopic management options. Successful use of numerous bronchoscopic techniques has been reported in the literature largely in the form of retrospective series and, at best, small prospective trials. …

Association Of Obesity With Hypertension, Wilbert S. Aronow

NYMC Faculty Publications

No abstract provided.

Is Bronchoscopy An Obsolete Tool In Cystic Fibrosis? The Role Of Bronchoscopy In Cystic Fibrosis And Its Clinical Use, Lisa Paul

NYMC Faculty Publications

Cystic fibrosis (CF) is a progressive life threatening multisystem genetic disease which affects the CF transmembrane conductance regulator channel. Respiratory causes remain the most common mortality in CF. With the onset of newborn screening, initiating treatments both for prophylaxis and disease management, optimizing nutritional support, and developing therapies targeting CF transmembrane conductance regulator protein, this has significantly changed the face of managing this devastating disease. Bronchoscopy and related procedures such as bronchoalveolar lavage (BAL), transbronchial biopsies, and protected brush sampling have been looked at in the management of CF as patients with CF continue to live longer with the help …

The Role Of Oral Vitamin D In Several Skin Diseases, Astri Adelia, Larisa Paramitha Wibawa, Adhimukti T. Sampurna, Windy K. Budianti, Farida Zubier

Journal of General - Procedural Dermatology and Venereology Indonesia

Vitamin D has many benefits for body and skin health. One of them is to regulate the immune system, both cellular and humoral. The pathogenesis of many skin diseases is associated with disturbance in regulation of cellular immune system. Research on the relationship between blood level of vitamin D and several diseases in dermatology is currently very advanced. Oral vitamin D is known to have many functions that play a role in the pathogenesis of several diseases of the skin. Therefore, its current use as a primary or supplemental therapy has been widely studied. Knowledge on various skin diseases with …

Principal Component Regression Analysis Of Nutrition Factors And Physical Activities With Diabetes, Ke-Sheng Wang, Ying Lu, Xin Xie, Shaoqing Gong, Chun Xu, Zhanxin Sha

Health & Biomedical Sciences Faculty Publications

The associations of nutrition factors and physical activities with adult diabetes are inconsistent; while most of these factors are inter correlated. The aims of this study are to overcome the disturbance of the multicollinearity of the risk factors and examine the associations of these factors with diabetes using the principal component analysis (PCA) and regression analysis with principal component scores (PCS). Totally, 659 adults with diabetes and 2827 non-diabetic were selected from the 2012 Health Information National Trends Survey (HINTS 4, Cycle 2). PCA was utilized to deal with multicollinearity of the risk factors. Weighted univariate and multiple logistic regression …

Cancer-Related Risk Factors And Incidence Of Major Cancers By Race, Gender And Region; Analysis Of The Nih-Aarp Diet And Health Study, Tomi Akinyemiju, Howard Wiener, Maria Pisu

Epidemiology and Environmental Health Faculty Publications

Background: Racial disparities in the incidence of major cancers may be attributed to differences in the prevalence of established, modifiable risk factors such as obesity, smoking, physical activity and diet.

Methods: Data from a prospective cohort of 566,398 adults aged 50–71 years, 19,677 African-American and 450,623 Whites, was analyzed. Baseline data on cancer-related risk factors such as smoking, alcohol, physical activity and dietary patterns were used to create an individual adherence score. Differences in adherence by race, gender and geographic region were assessed using descriptive statistics, and Cox proportional hazards models were used to determine the association between adherence and …

The Effects Of Perinatal Oxycodone Exposure On Behavioral Outcome In A Rodent Model, Thitinart Sithisarn, Sandra J. Legan, Philip M. Westgate, Melinda E. Wilson, Kristen Wellmann, Henrietta S. Bada, Susan Barron

Pediatrics Faculty Publications

Opiate addiction is now a major public health problem. Perinatal insults and exposure to opiates such as morphine in utero are well known to affect development of the hypothalamic–pituitary–adrenal axis of the offspring adversely and are associated with a higher risk of developing neurobehavioral problems. Oxycodone is now one of the most frequently abused pain killers during pregnancy; however, limited data are available regarding whether and how perinatal oxycodone exposure (POE) alters neurobehavioral outcomes of the offspring. We demonstrated that exposure to 0.5 mg/kg/day oxycodone in utero was associated with hyperactivity in adult rats in an open field. No significant …

Treating Diabetic Ketoacidosis With Subcutaneous Insulin?, Marlene Aziza Azar

Clinical Research in Practice: The Journal of Team Hippocrates

The author examines the evidence for treating diabetic ketoacidosis with subcutaneous insulin vs IV insulin.

Strategies To Improve Control Of Blood A1c In Diabetics, Jennifer Aronson, Leanne Bellino, Elizabeth Eisenhardt, Diane Bryant, Haley Pelletier, Internal Medicine Team, Adult Outpatient Clinic

MaineHealth Maine Medical Center

A1c monitoring is an important aspect of controlling the health of a diabetic patient. An adult internal medicine clinic noted that the percentage of their diabetic patients who had an A1c higher than 9 or no reading within the past year exceeded the national average. As a result, operational excellence methods were implemented with the overall goal to reduce their percentage to 18% or less.

A root cause analysis identified several deficiencies to includelack of essential equipment, variations in

staff education and the absence of daily reminders.

Post KPI implementations, an overall decrease in the percentage of patients with poorly …

Effect Of Flibanserin Treatment On Body Weight In Premenopausal And Postmenopausal Women With Hypoactive Sexual Desire Disorder: A Post Hoc Analysis., Susan G Kornstein, James A Simon, Stuart C Apfel, James Yuan, Krista A Barbour, Robert Kissling

Obstetrics and Gynecology Faculty Publications

Background: Flibanserin, a 5-HT_1A agonist and 5-HT_2A antagonist, is indicated for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. This post hoc analysis evaluated the effect of flibanserin treatment on body weight in premenopausal and postmenopausal women with HSDD.

Materials and Methods: This analysis included three 24-week, double-blind, placebo-controlled studies of flibanserin 100 mg each bedtime (qhs) in premenopausal women, a similarly designed study in postmenopausal women, and a 52-week, open-label extension study in premenopausal women.

Results: In a pooled analysis of premenopausal women, mean baseline body mass index (BMI) was 27.0 kg/m …

Estimates Of Burden And Consequences Of Infants Born Small For Gestational Age In Low And Middle Income Countries With Intergrowth-21(St) Standard: Analysis Of Cherg Datasets., Anne Cc Lee, Naoko Kozuki, Simon Cousens, Gretchen A Stevens, Hannah Blencowe, Mariangela F Silveira, Ayesha Sania, Heather E Rosen, Christentze Schmiegelow, Linda S Adair, Abdullah H Baqui, Fernando C Barros, Zulfiqar A Bhutta, Laura E Caulfield, Parul Christian, Siân E Clarke, Wafaie Fawzi, Rogelio Gonzalez, Jean Humphrey, Lieven Huybregts, Simon Kariuki, Patrick Kolsteren, John Lusingu, Dharma Manandhar, Aroonsri Mongkolchati, Luke C Mullany, Richard Ndyomugyenyi, Jyh Kae Nien, Dominique Roberfroid, Naomi Saville, Dianne J Terlouw, James M Tielsch, Cesar G Victora, Sithembiso C Velaphi, Deborah Watson-Jones, Barbara A Willey, Majid Ezzati, Joy E Lawn, Robert E Black, Joanne Katz

Global Health Faculty Publications

Objectives To estimate small for gestational age birth prevalence and attributable neonatal mortality in low and middle income countries with the INTERGROWTH-21st birth weight standard.

Design Secondary analysis of data from the Child Health Epidemiology Reference Group (CHERG), including 14 birth cohorts with gestational age, birth weight, and neonatal follow-up. Small for gestational age was defined as infants weighing less than the 10th centile birth weight for gestational age and sex with the multiethnic, INTERGROWTH-21st birth weight standard. Prevalence of small for gestational age and neonatal mortality risk ratios were calculated and pooled among these datasets at the regional level. …

Inflammation And Bone Mineral Density: A Mendelian Randomization Study, Jian V. Huang, C. Mary Schooling

Publications and Research

Osteoporosis is a common age-related disorder leading to an increase in osteoporotic fractures and resulting in significant suffering and disability. Inflammation may contribute to osteoporosis, as it does to many other chronic diseases. We examined whether inflammation is etiologically relevant to osteoporosis, assessed from bone mineral density (BMD), as a new potential target of intervention, or whether it is a symptom/biomarker of osteoporosis. We obtained genetic predictors of inflammatory markers from genome-wide association studies and applied them to a large genome wide association study of BMD. Using two-sample Mendelian randomization, we obtained unconfounded estimates of the effect of high-sensitivity C-reactive …

Estimates Of Burden And Consequences Of Infants Born Small For Gestational Age In Low And Middle Income Countries With Intergrowth-21st Standard: Analysis Of Cherg Datasets, Anne C C Lee, Naoko Kozuki, Simon Cousens, Gretchen A. Stevens, Hannah Blencowe, Mariangela F. Silveira, Ayesha Sania, Heather E. Rosen, Christentze Schmiegelow, Linda S. Adair, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

Objectives: To estimate small for gestational age birth prevalence and attributable neonatal mortality in low and middle income countries with the INTERGROWTH-21st birth weight standard.
Design: Secondary analysis of data from the Child Health Epidemiology Reference Group (CHERG), including 14 birth cohorts with gestational age, birth weight, and neonatal follow-up. Small for gestational age was defined as infants weighing less than the 10th centile birth weight for gestational age and sex with the multiethnic, INTERGROWTH-21st birth weight standard. Prevalence of small for gestational age and neonatal mortality risk ratios were calculated and pooled among these datasets at the regional level. …

Pharmacologic Or Genetic Targeting Of Glutamine Synthetase Skews Macrophages Toward An M1-Like Phenotype And Inhibits Tumor Metastasis., Erika M. Palmieri, Alessio Menga, Rosa Martín-Pérez, Annamaria Quinto, Carla Riera-Domingo, Giacoma De Tullio, D Craig Hooper, Wouter H. Lamers, Bart Ghesquière, Daniel W. Mcvicar, Attilio Guarini, Massimiliano Mazzone, Alessandra Castegna

Department of Cancer Biology Faculty Papers

Glutamine-synthetase (GS), the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR) activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation. As a result of these metabolic changes and HIF1α accumulation, GS-inhibited macrophages display an increased capacity to induce T cell recruitment, reduced T cell suppressive potential, and an impaired ability to foster endothelial …

Prognostic Value Of Routine Laboratory Variables In Prediction Of Breast Cancer Recurrence., Zhu Zhu, Ling Li, Zhong Ye, Tong Fu, Ye Du, Aiping Shi, Di Wu, Ke Li, Yifan Zhu, Chun Wang, Zhimin Fan

Department of Medical Oncology Faculty Papers

The prognostic value of routine laboratory variables in breast cancer has been largely overlooked. Based on laboratory tests commonly performed in clinical practice, we aimed to develop a new model to predict disease free survival (DFS) after surgical removal of primary breast cancer. In a cohort of 1,596 breast cancer patients, we analyzed the associations of 33 laboratory variables with patient DFS. Based on 3 significant laboratory variables (hemoglobin, alkaline phosphatase, and international normalized ratio), together with important demographic and clinical variables, we developed a prognostic model, achieving the area under the curve of 0.79. We categorized patients into 3 …

Linking Kindling To Increased Glutamate Release In The Dentate Gyrus Of The Hippocampus Through The Stxbp5/Tomosyn-1 Gene, Seth R. Batten, Elena A. Matveeva, Sidney W. Whiteheart, Thomas C. Vanaman, Greg A. Gerhardt, John T. Slevin

Psychology Faculty Publications

Introduction: In kindling, repeated electrical stimulation of certain brain areas causes progressive and permanent intensification of epileptiform activity resulting in generalized seizures. We focused on the role(s) of glutamate and a negative regulator of glutamate release, STXBP5/tomosyn-1, in kindling.

Methods: Stimulating electrodes were implanted in the amygdala and progression to two successive Racine stage 5 seizures was measured in wild-type and STXBP5/tomosyn-1^−/− (Tom^−/−) animals. Glutamate release measurements were performed in distinct brain regions using a glutamate-selective microelectrode array (MEA).

Results: Naïve Tom^−/− mice had significant increases in KCl-evoked glutamate release compared to naïve wild type as …

Abl Kinase Regulation By Braf/Erk And Cooperation With Akt In Melanoma, Aditi Jain, Rakshamani Tripathi, Courtney P. Turpin, Chi Wang, Rina Plattner

Pharmacology and Nutritional Sciences Faculty Publications

The melanoma incidence continues to increase, and the disease remains incurable for many due to its metastatic nature and high rate of therapeutic resistance. In particular, melanomas harboring BRAF^V600E and PTEN mutations often are resistant to current therapies, including BRAF inhibitors (BRAFi) and immune checkpoint inhibitors. Abl kinases (Abl/Arg) are activated in melanomas and drive progression; however, their mechanism of activation has not been established. Here we elucidate a novel link between BRAF^V600E/ERK signaling and Abl kinases. We demonstrate that BRAF^V600E/ERK play a critical role in binding, phosphorylating and regulating Abl localization and Abl/Arg activation …

Teen, Parent, And Clinician Expectations About Obesity And Related Conditions During The Annual Well-Child Visit, Andrew S. Bossick, Charles Barone, Gwen L. Alexander, Heather A. Olden, Tanya Troy, Andrea E. Cassidy-Bushrow

Journal of Patient-Centered Research and Reviews

Purpose: This study aimed to examine family (patient, parent/guardian) and clinician preferences for identification and management of obesity and obesity-related conditions during the well-child visit.

Methods: Four focus groups with teen patients (n = 16), four focus groups with parents (n = 15) and one focus group with providers (n = 12) were conducted using a structured moderator guide tailored to each population. Eligible patients had a well-child visit during the past 12 months and a diagnosis of overweight, obesity, hyperlipidemia or elevated blood pressure. Parents who attended their child’s well-child visit and whose child met the diagnostic …

Every Word, Every Gesture, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

Two nonverbal patients teach a novice clinician the power and often hidden impact of the physician-patient relationship.

Cardio-Metabolic Benefits Of Plant-Based Diets., Hana Kahleova, Susan Levin, Neal Barnard

Medicine Faculty Publications

Cardio-metabolic disease, namely ischemic heart disease, stroke, obesity, and type 2 diabetes, represent substantial health and economic burdens. Almost one half of cardio-metabolic deaths in the U.S. might be prevented through proper nutrition. Plant-based (vegetarian and vegan) diets are an effective strategy for improving nutrient intake. At the same time, they are associated with decreased all-cause mortality and decreased risk of obesity, type 2 diabetes, and coronary heart disease. Evidence suggests that plant-based diets may reduce the risk of coronary heart disease events by an estimated 40% and the risk of cerebral vascular disease events by 29%. These diets also …

Targeting Hepatic Heparin-Binding Egf-Like Growth Factor (Hb-Egf) Induces Anti-Hyperlipidemia Leading To Reduction Of Angiotensin Ii-Induced Aneurysm Development, Seonwook Kim, Lihua Yang, Seongu Kim, Richard G. Lee, Mark J. Graham, Judith A. Berliner, Aldons J. Lusis, Lei Cai, Ryan E. Temel, Debra L. Rateri, Sangderk Lee

Saha Cardiovascular Research Center Faculty Publications

Objective

The upregulated expression of heparin binding EGF-like growth factor (HB-EGF) in the vessel and circulation is associated with risk of cardiovascular disease. In this study, we tested the effects of HB-EGF targeting using HB-EGF-specific antisense oligonucleotide (ASO) on the development of aortic aneurysm in a mouse aneurysm model.

Approach and results

Low-density lipoprotein receptor (LDLR) deficient mice (male, 16 weeks of age) were injected with control and HB-EGF ASOs for 10 weeks. To induce aneurysm, the mice were fed a high fat diet (22% fat, 0.2% cholesterol; w/w) at 5 week point of ASO administration and infused with angiotensin …

The Oral Microbiome And Adverse Pregnancy Outcomes., Charles M. Cobb, Patricia J. Kelly, Karen B. Williams, Shilpa Babbar, Mubashir Angolkar, Richard J. Derman

Department of Obstetrics and Gynecology Faculty Papers

Significant evidence supports an association between periodontal pathogenic bacteria and preterm birth and preeclampsia. The virulence properties assigned to specific oral pathogenic bacteria, for example, Fusobacterium nucleatum, Porphyromonas gingivalis, Filifactor alocis, Campylobacter rectus, and others, render them as potential collaborators in adverse outcomes of pregnancy. Several pathways have been suggested for this association: 1) hematogenous spread (bacteremia) of periodontal pathogens; 2) hematogenous spread of multiple mediators of inflammation that are generated by the host and/or fetal immune response to pathogenic bacteria; and 3) the possibility of oral microbial pathogen transmission, with subsequent colonization, in the vaginal microbiome resulting from sexual …

A Life Course Examination Of The Physical Environmental Determinants Of Physical Activity Behaviour: A “Determinants Of Diet And Physical Activity” (Dedipac) Umbrella Systematic Literature Review, Angela Carlin, Camille Perchoux, Anna Puggina, Katina Aleksovska, Christoph Buck, Con Burns, Greet Cardon, Simon Chantal, Donatella Ciarapica, Giancarlo Condello, Tara Coppinger, Cristina Cortis, Sara D’Haese, Marieke De Craemer, Andrea Di Blasio, Sylvia Hansen, Licia Iacoviello, Johann Issartel, Pascal Izzicupo, Lina Jaeschke, Martina Kanning, Aileen Kennedy, Jeroen Lakerveld, Fiona Chun Man Ling, Agnes Luzak, Giorgio Napolitano, Julie Anne Nazare, Tobias Pischon, Angela Polito, Alessandra Sannella, Holger Schulz, Rhoda Sohun

Publications

Background: Participation in regular physical activity is associated with a multitude of health benefits across the life course. However, many people fail to meet PA recommendations. Despite a plethora of studies, the evidence regarding the environmental (physical) determinants of physical activity remains inconclusive. Objective: To identify the physical environmental determinants that influence PA across the life course. Methods: An online systematic literature search was conducted using MEDLINE, ISI Web of Science, Scopus and SPORTDiscus. The search was limited to studies published in English (January 2004 to April 2016). Only systematic literature reviews (SLRs) and meta-analyses (MAs) of observational studies, that …

Progress And Priorities For Reproductive, Maternal, Newborn, And Child Health In Kenya: A Countdown To 2015 Country Case Study, Emily C. Keats, Anthony Ngugi, William Macharia, Nadia Akseer, Emma Nelima Khaemba, Zaid Ahmad Bhatti, Arjumand Rizvi, John Tole, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

Background: Progress in reproductive, maternal, newborn, and child health (RMNCH) in Kenya has been inconsistent over the past two decades, despite the global push to foster accountability, reduce child mortality, and improve maternal health in an equitable manner. Although several cross-sectional assessments have been done, a systematic analysis of RMNCH in Kenya was needed to better understand the push and pull factors that govern intervention coverage and influence mortality trends. As such, we aimed to determine coverage and impact of key RMNCH interventions between 1990 and 2015.
Methods: We did a comprehensive, systematic assessment of RMNCH in Kenya from 1990 …

Structure-Based Design Of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses To A Conserved Epitope, Brian G. Pierce, Elisabeth N. Boucher, Kurt H. Piepenbrink, Monir Ejemal, Chelsea A. Rapp, William D. Thomas Jr, Eric J. Sundberg, Zhiping Weng, Yang Wang

Food for Health: Publications

Despite recent advances in therapeutic options, hepatitis C virus (HCV) remains a severe global disease burden, and a vaccine can substantially reduce its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response; thus, an effective vaccine must target conserved, functionally important epitopes. Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412 to 423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope. This resulted in epitope-based immunogens based on a cyclic defensin protein, as …

Diabetes In Sub-Saharan Africa: From Clinical Care To Health Policy., Rifat Atun, Justine I. Davies, Edwin A.M. Gal, Till Bärnighausen, David Beran, Andre Pascal Kengne, Naomi S. Levitt, Florence Mangugu, Moffat J. Nyirenda, Graham D. Ogle, Kaushik Ramaiya

Paediatrics and Child Health, East Africa

Rapid demographic, sociocultural, and economic transitions are driving increases in the risk and prevalence of diabetes and other non-communicable diseases (NCDs) in sub-Saharan Africa. The impacts of these transitions and their health and economic consequences are evident. Whereas, in 1990, the leading causes of death in sub-Saharan Africa were HIV/AIDS, lower respiratory infections, diarrhoeal diseases, malaria, and vaccine-preventable diseases in children, in more recent years, cardiovascular diseases and their risk factors are replacing infectious diseases as the leading causes of death in this region, and rates of increase of cardiovascular risk factors are predicted to be greater in sub-Saharan Africa …

Brain Microvascular Injury And White Matter Disease Provoked By Diabetes-Associated Hyperamylinemia, Han Ly, Nirmal Verma, Fengen Wu, Miao Liu, Kathryn E. Saatman, Peter T. Nelson, John T. Slevin, Larry B. Goldstein, Geert Jan Biessels, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

OBJECTIVE: The brain blood vessels of patients with type 2 diabetes and dementia have deposition of amylin, an amyloidogenic hormone cosecreted with insulin. It is not known whether vascular amylin deposition is a consequence or a trigger of vascular injury. We tested the hypothesis that the vascular amylin deposits cause endothelial dysfunction and microvascular injury and are modulated by amylin transport in the brain via plasma apolipoproteins.

METHODS: Rats overexpressing amyloidogenic (human) amylin in the pancreas (HIP rats) and amylin knockout (AKO) rats intravenously infused with aggregated amylin were used for in vivo phenotyping. We also carried out biochemical analyses …