14 Howard Haimes

53 %
47 %
Information about 14 Howard Haimes
Entertainment

Published on November 19, 2007

Author: Cubemiddle

Source: authorstream.com

Slide1:  This presentation is copyright Ó2007 by Alteon Inc. Any duplication, use or distribution of this presentation is strictly prohibited without prior written authorization from Alteon Inc. ALTEON Protein Glycation and the Cardiovascular System Edmonton Aging Symposium Howard B. Haimes, Ph.D. Executive Director, Preclinical Sciences March 30-31, 2007 Breakthrough Medicines For Cardiovascular Aging and Complications of Diabetes Slide2:  General Introduction to The “A.G.E. Pathway” A.G.E.s Form and….:  A.G.E.s Form and…. Amino Acids Sugar Lipid Schiff Base Amadori Product (e.g. HbAlc) Serum and Tissue AGEs Dicarbonyl Intermediates + Polyol Pathway [ox] [ox] glu glu [ox] ….Induce Inflammation:  ….Induce Inflammation  IL-1  TNF  TGFβ  NFκβ  eNOS Pathologies: Vascular Stiffening Chronic Heart Failure Nephropathy Source: Diabetes, Brownlee, Vol. 54, June 2005 Intracellular protein glycation AGE precursors Glucose Matrix Intracellular transducers Transcription factors Glucose DNA Transcription AGE receptor AGE plasma proteins AGE receptor ROS NF-β Macrophage mesangial cell mRNA Proteins Integrins Endothelial cell RNA  The Role of A.G.E.s in Ventricular Remodeling:  The Role of A.G.E.s in Ventricular Remodeling A variety of factors including diabetes, hypertension and aging lead to cardiac hypertrophy This hypertrophy is primarily due to enhanced deposition of type I and III collagens in the myocardium Glycation causes an upregulation of sclerotic cytokines such as CTGF and TGFß Glycation of Extracellular matrix molecules restricts normal turnover Slide6:  Cardiovascular Studies with Alagebrium in Rodents Alagebrium Reduces LV Mass:  Alagebrium Reduces LV Mass Aged SHR Rats (45 Weeks) 0.01, 0.1, 1.0 and 10mg/kg daily for 20 weeks Confirmed 1 mg/kg/day as optimal dose Susic, D et al Cardiovascular and Renal Effects of a Collagen Cross-Link Breaker (ALT 711) in Adult and Aged Spontaneously Hypertensive Rats. AJH 2004; 17:328-333 Left Ventricular Mass Reduction:  Left Ventricular Mass Reduction * p<0.05 when compared to controls Adapted from: Susic, D et al Cardiovascular and Renal Effects of a Collagen Cross-Link Breaker (ALT 711) in Adult and Aged Spontaneously Hypertensive Rats. AJH 2004; 17:328-333 Alagebrium Attenuates Diabetic Cardiomyopathy:  Alagebrium Attenuates Diabetic Cardiomyopathy STZ Induced Diabetes in Sprague Dawley Rats for 32 weeks Treatment with alagebrium (10 mg/kg) beginning at week 16 for 16 weeks Candido R et al A Breaker of Advanced Glycation End Products Attenuates Diabetes-Induced Myocardial Structural Changes Circ Res 2003; 92:785-792 Alagebrium Attenuates Diabetic Cardiomyopathy:  Alagebrium Attenuates Diabetic Cardiomyopathy Alagebrium Restores Collagen Solubility:  Alagebrium Restores Collagen Solubility % LV Collagen Solubility Adapted from: Candido R et al A Breaker of Advanced Glycation End Products Attenuates Diabetes-Induced Myocardial Structural Changes Circ Res 2003; 92:785-792 Alagebrium Attenuates mRNA RAGE Expression:  Alagebrium Attenuates mRNA RAGE Expression Adapted from: Candido R et al A Breaker of Advanced Glycation End Products Attenuates Diabetes-Induced Myocardial Structural Changes, Circ Res 2003; 92:785-792 Intervention with Alagebrium Reverses Glycation Induced Deficits in Structure and Function:  Intervention with Alagebrium Reverses Glycation Induced Deficits in Structure and Function Decrease in LV mass over time Return of collagen solubility by MMPs Decreased expression of types I & III collagens Decrease in sclerotic cytokines Decrease in inflammatory stimulus Alagebrium Decreases Myocardial Fibrosis and Improves Endothelial Function:  Alagebrium Decreases Myocardial Fibrosis and Improves Endothelial Function DAHL salt sensitive rat Alagebrium treatment for 4 weeks at 10 mg/kg/day PO Veronesi, M et al ALT-711, A Collagen Cross-Link Breaker, Decreases Myocardial Fibrosis and Improves Endothelial Dysfunction in Hypertensive DAHL Salt Rats 2001 AHA Annual Fall Conference and Scientific Sessions of the Council for High Blood Pressure Research Alagebrium Decreases Myocardial Fibrosis and Improves Endothelial Function:  Alagebrium Decreases Myocardial Fibrosis and Improves Endothelial Function Intervention with Alagebrium:  Intervention with Alagebrium Reduces tissue and serum A.G.E.s Reverses collagen solubility Reduces urinary albumin excretion Reduces inflammatory and cytokine expression Alagebrium Restores Diastolic, Systolic and Endothelial Function :  Alagebrium Restores Diastolic, Systolic and Endothelial Function Aging Rat Study conducted at Johns Hopkins School of Medicine (unpublished results) Evaluated effects of exercise +/- treatment with alagebrium Hemodynamic evaluations The Effect of Aminoguanidine and Alagebrium on AGE and RAGE Expression in Atherosclerotic Plaque:  The Effect of Aminoguanidine and Alagebrium on AGE and RAGE Expression in Atherosclerotic Plaque The Effect of Alagebrium on Urinary Protein Excretion:  The Effect of Alagebrium on Urinary Protein Excretion Pressure-Volume Loops in Young and Old Rats:  Pressure-Volume Loops in Young and Old Rats The Effect of Alagebrium on Diastolic Function:  The Effect of Alagebrium on Diastolic Function The Effect of Alagebrium on Systolic Function:  The Effect of Alagebrium on Systolic Function The Effect of Alagebrium on Cardiac Contractility:  The Effect of Alagebrium on Cardiac Contractility The Effect of Alagebrium on Endothelial Function:  The Effect of Alagebrium on Endothelial Function Intervention with Alagebrium Restores Functional Properties to Tissues and Organs:  Intervention with Alagebrium Restores Functional Properties to Tissues and Organs Reversal of LV Mass Improvements in systolic and diastolic properties Decreased plaque progression in atherosclerosis Restoration of Nitric Oxide production and bioavailability Slide26:  Cardiovascular Studies with Alagebrium in Canines Alagebrium Treatment Reduces Cardiac Collagen and Improves Function:  Alagebrium Treatment Reduces Cardiac Collagen and Improves Function Male mongrel dogs 9-12 years Induction of diabetes with alloxan monohydrate 25-35 mg/kg Treatment with ALT 711 1mg/kg daily for 1 month Hemodynamic studies by 2-D echo and Millar conductance catheter Liu, J, et al Glycation end-product cross-link breaker reduces collagen and improves cardiac function in aging diabetic heart. A, J Physiol Heart Circ Physiol. 2003; 285L 2857-2591 Alagebrium Reduces LV Mass:  Alagebrium Reduces LV Mass LV Mass, g/kg P<0.05 vs. Aging P< 0.05 vs. Aging and Diabetes Liu, J, et al Glycation end-product cross-link breaker reduces collagen and improves cardiac function in aging diabetic heart. A, J Physiol Heart Circ Physiol. 2003; 285L 2857-2591 Alagebrium Reverses Type I Collagen Deposition:  Alagebrium Reverses Type I Collagen Deposition Alagebrium Reverses Type III Collagen Deposition :  Alagebrium Reverses Type III Collagen Deposition Alagebrium Restores Collagen Solubility:  Alagebrium Restores Collagen Solubility Alagebrium Restores LV Function:  Alagebrium Restores LV Function P<0.05 vs. Aging P<0.05 vs. Aging and Diabetes Adapted from: Liu, J, et al Glycation end-product cross-link breaker reduces collagen and improves cardiac function in aging diabetic heart. A, J Physiol Heart Circ Physiol. 2003; 285L 2857-2591 LVEF % Alagebrium Reverses Functional Deficits in the Heart:  Alagebrium Reverses Functional Deficits in the Heart Improves vascular compliance Decreases LV mass Improves systolic and diastolic parameters Restores tissues and organs to a more youthful, functional state Alagebrium Reverses Myocardial Stiffness:  Alagebrium Reverses Myocardial Stiffness Male mongrel dogs 22-32 kg 1 mg/kg ALT 711 PO daily for one month Baseline and endpoint hemodynamic measurements Asif M. et al. An advanced glycation endproduct cross-link breaker can reverse age-related increases in myocardial stiffness. PNAS 2000 97(6); 2809-2913 Slide35:  (volume loaded) 0 5 10 15 20 25 30 35 40 0 10 20 30 40 50 60 70 80 90 100 End-Diastolic Volume Index (ml/m2) End-Diastolic Pressure (mm Hg) Low Volume, High Pressure High Volume, Low Pressure Male mongrel dogs. ALT-711: 1 mg/kg, oral, 4 weeks Adapted from Asif et al, PNAS 2000 Untreated Aged Dogs Young Dogs Control Short-Term Dosing With Alagebrium Restores Flexibility In The Left Ventricle In Aged Dogs Slide36:  Cardiovascular Studies with Alagebrium in Primates Alagebrium Improves Arterial and Ventricular Properties:  Alagebrium Improves Arterial and Ventricular Properties Male non diabetic Rhesus monkeys 21+/- 3.6 years ALT 711 1.0 mg/kg every other day for 3 weeks (IM) Arterial and ventricular properties measured Vaitekevicius, P et al A cross-link breaker has sustained effects on arterial and ventricular properties in older Rhesus monkeys PNAS 2001; 98(3): 1171-1175 Alagebrium Improves Arterial and Ventricular Structure and Function:  Alagebrium Improves Arterial and Ventricular Structure and Function Slide39:  Cardiovascular Studies with Alagebrium in Humans Key Clinical Findings for Alagebrium in Heart Failure:  Key Clinical Findings for Alagebrium in Heart Failure Meaningful reduction in left ventricular mass (p=0.036), in unprecedented timeframe Marked improvement in initial phase of left ventricular diastolic filling (p=0.045) Statistically significant improvements in multiple QOL measurements (p < 0.01) Sickest patient population (class III heart failure) benefited most Source: Kitzman, Zile, et al; Presented as Poster at Society of Geriatric Cardiology Annual Meeting, 2003 *Distensibility Improvement and Remodeling in Diastolic Heart Failure DIAMOND Study Source: Thohan, Koerner, et al; Presented as Poster at the American Heart Association Annual Meeting, 2005 Patients with Impaired Ejection Fraction and Diastolic Dysfunction: Efficacy and Safety Trial of Alagebrium PEDESTAL Study Improvements observed for: Diastolic function (E/A, DT, IVRT) Hemodynamics (LAP, PASP) LV remodeling (LAV, LVEDV, LV mass) NYHA score No alterations in heart rate, blood pressure or physical exam Slide41:  ALTEON This presentation is copyright Ó2007 by Alteon Inc. Any duplication, use or distribution of this presentation is strictly prohibited without prior written authorization from Alteon Inc. 6 Campus Drive Parsippany, NJ 07054 Tel: (201) 934-5000 Fax: (201) 934-8880 AMEX: ALT www.alteon.com

Add a comment

Related presentations

Related pages

Howard M. Haimes, Inc - BuildZoom

Howard M. Haimes, Inc in New York, NY holds a General Contractor Registered, Cn Construction license (002838) according to the New York license board.
Read more

Howard Haimes - Citations

Howard Haimes. AstraZeneca, London . Human Biology . 24.16 . Connect. Overview Contributions Info Stats . Citations. ... Cited in 14 publications:
Read more

Howard M. Haimes, Inc. Review - CONTRACTORS-GENERAL in New ...

BBB has determined that Howard M. Haimes, Inc. meets BBB accreditation standards, which include a commitment to make a good faith effort to resolve any ...
Read more

Howard Haimes - Pipl

Information about Howard Haimes from New York, Massachusetts, Washington and other places. Profile Photos, Address History, Phone Numbers, Relatives ...
Read more

Duane Michals - Checkerboard Film Foundation

Film Details. B&W/COLOR, 14 MINUTES YEAR PRODUCED: 1978 PRODUCER & DIRECTOR: Edgar B. Howard Theodore R. Haimes
Read more

Howard M Haimes Inc in New York, New York with Reviews ...

Find 654 listings related to Howard M Haimes Inc in New York on YP.com. See reviews, photos, directions, phone numbers and more for Howard M Haimes Inc ...
Read more

Speak with Howard Haimes - Askvisory Expert Advisor

Howard Haimes Askvisory Expert Advisor: United States, Natick www.askvisory.com/hhaimes : Send Message | Video/Voice Call | Start Chat. Why ...
Read more

Michael Haimes of Coral Springs, Florida Arrested for ...

Haimes, 29, was book — September 14, ... Michael Haimes of Coral Springs, Florida Arrested for Animal ... Howard James Fowler Jr. of Delray Beach and ...
Read more

Howard Haimes - Publications - ResearchGate

ResearchGate is a network dedicated to science and research. Connect, collaborate and discover scientific publications, jobs and conferences. All for free.
Read more