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Manning & Kass, Ellrod, Ramirez, Trester LLP. Manning & Kass, Ellrod, Ramirez, Trester LLP
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1 HARMONIE HONORS 2013 SUBMISSION Los Angeles 801 S. Figueroa Street, 15th Floor Los Angeles, CA Tel: (213) Fax: (213) Orange County MacArthur Blvd., Suite 900 Irvine, CA Tel: (949) Fax: (949) San Diego 550 West C Street, Suite 1900 San Diego, CA Tel: (619) Fax: (619)
2 TABLE OF CONTENTS Click on any of the links below to learn more about. FIRM PROFILE... 3 General Background... 3 Firm Honors... 3 Individual Attorney Honors... 3 ATTORNEY HONOR PAGES (LOS ANGELES)... 4 Dennis B. Kass... 4 Anthony J. Ellrod... 5 Eugene P. Ramirez... 5 Mildred K. O'Linn... 7 Lou Pappas... 8 James J. Perkins... 9 ATTORNEY HONOR PAGES (ORANGE COUNTY)...10 Scott Wm. Davenport Lawrence D. Esten ATTORNEY HONOR PAGES (SAN DIEGO)...12 Marguerite Lieu Jonak John D. Marino ATTORNEY HONOR PAGES (SAN FRANCISCO)...14 R. Adam Ellison D. Hiep Truong ATTORNEY HONOR PAGES (SCOTTSDALE)...17 Robert B. Zelms Debora L. Verdier... 18
3 FIRM PROFILE General Background Since 1994, has delivered exceptional results. Comprised of over 140 lawyers, we have represented clients in thousands of trials, appeals, and transactions across dozens of industries. We are renowned for our work and built one of the most well-respected law firms in the western U.S. Our firm s achievements stem from our commitment to collaboration. Regardless of size, we provide each client with a talented team of attorneys who work collectively to serve the client s needs. This unique approach yields cost-effective service and favorable results. Consequently, the firm has established a loyal client base that spans the Nation. Firm Honors Honor 2013 NLJ350 Firm 2013 Daily Journal s 50 Largest Law Firms 2012 California Lawyer s 50 Largest Law Firms 2011 California Lawyer s 50 Largest Law Firms Individual Attorney Honors # of Honor attorneys 1 25 Top Municipal Attorneys of the Year 2 Executives/Officers on State Bar committees 2 Litigation Counsel of America 2 Certified Estate Planning, Trust & Probate Law Specialists (State Bar of California) 5 Certified Appellate Law Specialists (State Bar of California) 6 Certified Workers' Compensation Law Specialists (State Bar of California) 7 Members of ABOTA 14 Members of DRI 16 Super Lawyers 16 AV Preeminent 20 Rising Stars 1 International Association of Defense Counsel 3 CLM Members 3 Page HARMONIE HONORS SUBMISSION
4 ATTORNEY HONOR PAGES (LOS ANGELES) Dennis B. Kass Dennis B. Kass is a founding partner at Manning & Kass, Ellrod, Ramirez, Trester, LLP. Mr. Kass has received a number of honors for his trial skills, including: 1999 IASIU Southern California Chapter Defense Attorney of the Year; 2001 California Lawyer Attorney of the Year for Civil Litigation (CLAY Award); 2002 Loyola Trial Lawyer of the Year; and 2004, 2005, 2006, 2007, 2008, 2009 and 2013 Los Angeles Magazine Super Lawyer. Mr. Kass heads the firm s Complex Litigation Team. The team s focus includes mass torts and high exposure personal injury matters. Mr. Kass also has extensive experience in the area of transportation litigation. Mr. Kass represents many trucking and other transportation clients, including serving as monitoring counsel for high exposure matters. The team also specializes in the handling of class action defense and defending Unfair Business Practice Claims (Business and Professions Code 17200). Mr. Kass gained notoriety in the area of insurance fraud litigation and is counsel to IASIU Southern California Chapter and on the CLM Fraud Committee. Mr. Kass has been featured in the New York Times, Los Angeles Times, the Daily Journal, and scores of other periodicals, as well as on television and radio for his role as lead counsel in numerous whistle-blower actions where insurance companies have sued professionals, including attorneys and doctors, for their role in large fraud rings. Mr. Kass prevailed in the first jury trial under California s Whistle-Blower law, obtaining an $8.2 million jury verdict against the defendant doctors. Mr. Kass was also lead counsel on the first state whistle-blower action which was based upon civil claims. Mr. Kass also has extensive experience in the area of insurance fraud litigation. He has been called upon by various insurance companies to assist in the prosecution of complex and sophisticated fraud rings. He is also involved in training professionals in a variety of subject areas, lecturing across the country on subjects including insurance fraud related areas, insurance bad faith, and insurance coverage issues. Mr. Kass has been called as an expert witness on behalf of the insurance industry, testifying before the Judiciary and Insurance Committees in the California State Assembly, as well as testifying before the State Senate Insurance Committee. His testimony focused on an insurance code statute that he assisted in drafting. Mr. Kass has also been called upon to testify before the State Senate Insurance Committee on other insurance issues, and he has also helped draft proposed anti-fraud legislation. 4 Page HARMONIE HONORS SUBMISSION
5 Mr. Kass has served as both an arbitrator and as a mediator since Mr. Kass is the author of the following articles: Offensive Weapons in the War Against Insurance Fraud; Blowing the Whistle on Insurance Fraud; To Scan or Not to Scan: The Move to Paperless Claims Files; Revealing Policy Limits Pre-Litigation; Best Claims Practices for Settling Wrongful Death Actions Pre-litigation - Where Did Those Heirs Come From? and How Do We Settle a Wrongful Death Case Post Moody? Mr. Kass graduated from UCLA in 1984 with a joint degree in Political Science and Psychology. He graduated from Loyola Law School in Mr. Kass has served as a mentor for law students for many years. Dennis is also a member of industry-specific groups, including the Transportation Lawyers Association (TLA) and the California Trucking Association (CTA). Anthony J. Ellrod Anthony J. Ellrod is a partner in the firm s Los Angeles office. Mr. Ellrod holds an AV rating, the highest rating available under the Martindale-Hubbell Peer Review Rating System, indicating that he is considered by others in the legal community to possess "very high to preeminent" legal ability and "very high" ethical standards. In addition, Mr. Ellrod is recognized as one of California's most outstanding lawyers. In 2005, 2006, 2007, 2008, 2009, 2010 and 2011 he was selected as a "Super Lawyer" by Law & Politics, an organization that honors the top 5% of the California Bar based on a detailed peer review survey, followed by a blue ribbon panel review. In 2009, 2010 and 2011 he was further honored by being included as a "Super Lawyer" in the Corporate Counsel Edition, and in 2010 by inclusion as a "Super Lawyer" in the Business Edition. In 2010, 2011 and 2012 he was selected Pasadena Magazine "Top Attorney" in Business Law/Litigation. Mr. Ellrod is a member of the American Board of Trial Advocates ("ABOTA"), an invitation-only organization consisting of members that must have at least five years of active experience as trial lawyers, have tried at least 10 civil jury trials to conclusion and possess additional litigation experience, and exhibit the virtues of civility, integrity and professionalism. Mr. Ellrod is also a member of the Association of Southern California Defense Counsel, the Association of Business Trial Lawyers, the Defense Research Institute ("DRI"), the Professional Liability Underwriting Society (PLUS), and the International Health, Racquet & Sportsclub Association. He is admitted to practice law before all California State Courts, the United States District Courts for the Northern, Central and Southern Districts of California, the 9th Circuit U.S. Court of Appeal, and the Supreme Court of the United States. Eugene P. Ramirez Eugene P. Ramirez, a founding member of the firm, graduated from Whittier College School of Law (J.D., 1987), where he was Notes & Comments Editor of the Law Review, a member of the Moot Court Honors Board and President of the Student Bar Association. At Whittier, he received an award as the Best Oral Advocate and the Outstanding Moot Court Graduate Award. He received his undergraduate degree in 5 Page HARMONIE HONORS SUBMISSION
6 Political Science from California State University, Long Beach (B.A., 1983), where he minored in Criminal Justice & Public Policy. Before joining the firm, Mr. Ramirez worked as a Deputy District Attorney for the L.A. County District Attorney's Office, where he conducted numerous misdemeanor and felony jury trials, including murder trials. He has also worked as a reserve police officer for the Whittier Police Department and the Monterey Park Police Department. He serves as an advisor to several public entities on the issues of use of force, canine and SWAT issues and policies and procedures. Mr. Ramirez has acquired significant expertise on civil liability arising out of the use of police dogs in law enforcement by winning several cases, and has lectured widely on the subject to police departments nationwide. He has provided training to thousands of canine officers and supervisors, from around the country and Canada, over the past 20 years. He is General Counsel for the United States Police Canine Association and has authored several articles for the USPCA's "Canine Courier." Mr. Ramirez is also experienced in defending SWAT Teams in civil liability cases. He is an instructor on liability issues for the Los Angeles County Sheriff s Department s Basic SWAT School. He is also an instructor for the California Association of Tactical Officers (CATO) and for the National Tactical Officers Association (NTOA). He was a member of the State Attorney General s Blue Ribbon SWAT Committee, and he was a member of POST s Executive Advisory Committee for SWAT Teams. He was a member of the LAPD Board of Inquiry, which examined LAPD SWAT operations. He is an approved California POST instructor. Mr. Ramirez was profiled in the April 2003, California Lawyer Magazine, for his work in defending law enforcement. He was honored with the 2004 Lifetime Achievement Award from the Association of Los Angeles Deputy Sheriffs (ALADS). He has been named as a Super Lawyer for Southern California. This award only goes to the top 5% of attorneys in the Los Angeles/Orange County Bar. He was also named to the distinguished American Board of Trial Advocates (ABOTA), an award only bestowed upon proven trial attorneys. He was selected as the Los Angeles County Sheriff's Department s Trial Lawyer of the Year in 1993 and, 2006, by two different Sheriffs. He was selected as the 2009 Alumni Attorney of the Year for Whittier School of Law. Eugene Ramirez was also named to the Daily Journal's Top 25 Municipal Lawyers list for 2011 and most recently, December 5, This premier list is composed of the leading lawyers in California who represent cities, counties, and local districts. The Daily Journal Corporation compiles the list of outstanding attorneys in the field of municipal law by collecting peer recommendations and conducting a competitive evaluation process. This is the second consecutive year in which Eugene Ramirez was named to this list. 6 Page HARMONIE HONORS SUBMISSION
7 Mr. Ramirez is frequently invited to speak to law enforcement agencies across the United States on use of force, handling high profile cases and risk management issues. Mildred K. O'Linn Mildred K. O'Linn is a partner in the Los Angeles office of Manning & Kass, Ellrod, Ramirez, Trester LLP. Ms. O'Linn has an unparalleled background as an attorney and technical expert in law enforcement civil liability, peace officer training and tactics, sexual harassment and employment litigation, and the defense of municipal entities. Ms. O'Linn received her Juris Doctor from the University of Akron School of Law in Akron, Ohio (1986) and her undergraduate degree in criminal justice from the Honors College, Kent State University in Kent, Ohio (BS, cum laude, 1982). Ms. O'Linn has been licensed to practice law in California, Texas, and Ohio. In addition to her varied civil practice as a trial attorney, Ms. O'Linn was a peace officer for eight years at the Kent State University Police Department. Subsequently, she served as the Legal and Technical Advisor for the Law Enforcement Television Network, Inc. (LETN). In February, 1992 she was appointed as a member of the California Commission on Peace Officer Standards and Training "Use of Force Committee." She also served as a member of the California Peace Officers' Association committee to develop a "Use of Force Model Policy"; was a member of the Los Angeles Police Department "Use of Force Training Review Committee"; and served on the Los Angeles Police Department's "Civilian Martial Arts Advisory Panel" in development of the Arrest and Control curriculum. Currently she serves as the 2nd Vice President for the Southern California Chapter of the California Association of Police Training Officers ( CAPTO ). While a police officer, Ms. O'Linn served as the chairperson of Unarmed Self-Defense for Basic Police Training for the Ohio Peace Officer Training Council. As a recognized expert in the use of force, Ms. O'Linn has served as an expert witness in civil litigation and has been called upon by numerous agencies across the country to serve as a consultant on police training issues, policy formulation and procedures and in review of high profile incidents. She also has the distinction of being one of the original founding members of the American Society of Law Enforcement Trainers, serving as the original Legal Advisor and subsequently serving as a member of the Executive Board from 1992 to One of the unique aspects of Ms. O'Linn's background is her extensive defensive tactics knowledge combined with her experience managing a regional police training academy, basic and in-service training programs, and field training officer program. Ms. O'Linn has been certified as an instructor and instructor-trainer in numerous police self-defense systems, including certifications as an International PR-24 police baton instructor, a TASER instructor and a National Instructor in the Lateral Vascular Neck Restraint System, Pressure Point Control Tactics and police physical fitness. Ms. O'Linn has provided training to thousands of law enforcement personnel including use of force instructors, supervisors/management and line personnel from state, local, and federal 7 Page HARMONIE HONORS SUBMISSION
8 law enforcement agencies throughout the country in a wide variety of topics including: use of force, civil liability, sexual harassment, preparing to be an expert witness and expert witness testimony, as well as hands on physical skills. Ms. O Linn has received awards and acknowledgments for excellence in representation and for her contributions to the defense of the law enforcement community from various agencies. In 2005 she was the Los Angeles County Deputy Sheriff's Association s recipient of the Award for Civilian Leadership. In December, 2006 Ms. O Linn received a Meritorious Service Award from the City of Gretna, Louisiana Police Department for her assistance to law enforcement in the aftermath of Hurricane Katrina. Ms. O Linn has been repeatedly recognized since 2004 as a Southern California Super Lawyer - an award that only goes to the top 5% of attorneys in the Los Angeles/Orange County Bar. In 2009 Ms. O'Linn was accepted as a member of the distinguished American Board of Trial Advocates (ABOTA), an award only bestowed upon proven trial attorneys. In 2012 the Orange County Sheriff s Department nominated Ms. O Linn for a national Law Enforcement Trainer of the Year Award. In 2006, Ms. O Linn was requested to take over the defense in a highly notable products liability case TASER International just 10 days before trial. In November, 2006 a defense verdict was rendered in that matter on behalf of the LAPD and TASER and the case was selected as one of the top 100 defense verdicts nationally for Lou Pappas Lou Pappas has a distinguished record of successfully defending complex, high exposure jury trials in courtrooms venued throughout the State of California. For over 28 years, Mr. Pappas impressive trial experience in healthcare has ranged from defending the individual clinician in medical malpractice actions involving catastrophic injury, wrongful death or birth injuries, to representing major medical centers and public entities. While his statewide trial practice continues to be focused on the healthcare industry, Mr. Pappas has developed expertise in the representation and defense of clients, including several Fortune 50 Companies, in general liability litigation and trials where a significant portion of the damages involve medical related issues. Mr. Pappas holds the rank of Associate in ABOTA (American Board of Trial Advocates). Mr. Pappas spent the first 17 years of his legal career with one of the largest firms in California that was dedicated exclusively to the defense of healthcare providers. He joined, a full-service AV-rated law firm with more than 140 attorneys in five offices located in two states, in 2002 to develop a Health Care Practice Group. As the director of the firms Healthcare Practice Group, Mr. Pappas team specializes in the representation of physicians, dentists, nurses, chiropractors, hospitals, surgery centers, health care institutions, county and state governmental agencies and allied health professionals in malpractice lawsuits, institutional provider liability, including managed care litigation, elder abuse, medical and allied health board hearings, administrative hearings and drug/medical device litigation. 8 Page HARMONIE HONORS SUBMISSION
9 Mr. Pappas is a graduate of California State Polytechnic University, Pomona (B.A., Political Science) and of Southwestern University School of Law (J.D.). He is admitted to practice before all the United States District Courts of California, including the Ninth Circuit U.S. Court of Appeals. He is a member of the State Bar of California, ABOTA (American Board of Trial Associates), the Los Angeles County Bar Association, the Association of Southern California Defense Counsel, the DRI and the Eighth Street Lawyers. James J. Perkins James J. Perkins is a partner in the firm s Los Angeles office. He is a graduate of the Santa Clara University School of Law (JD 1986) and the University of California, Santa Cruz (BA 1983). The first two years of his career were devoted to defending large reserve tort cases. He then spent two years defending insurers in bad faith actions. Since that time, he has dedicated his practice to fighting fraud, especially in the automobile insurance arena. Mr. Perkins has taken thousands of depositions and examinations under oath, arbitrated hundreds of cases, and has taken over fifty successful jury verdicts. Mr. Perkins is a member of ABOTA, an invitation-only organization consisting of members that must have at least five years of active experience as trial lawyers, have tried at least 10 civil jury trials to conclusion and possess additional litigation experience, and exhibit the virtues of civility, integrity and professionalism. Mr. Perkins leads a successful team of attorneys that specialize in the evaluation and defense of first and third party SIU claims. These include stolen vehicle claims, with the related incorporation of evidence relating to: transponder and other anti-theft systems, forensic expert opinions, airbags, call log records, LPR, ISO, and ECU records. Homeowner, fire loss, and automobile bodily injury claims are also regularly handled, including investigation into possibly orchestrated and excessive billing and other inappropriate claims practices by claimants and those working with them. This area of practice routinely incorporates policy analysis and delivering coverage opinions to our clients. Mr. Perkins is also a member of a successful team of attorneys, headed by Dennis B. Kass, that prosecute Insurance Code section whistleblower cases and other actions against attorneys, doctors, organized crime members, chiropractors, body shop owners, cappers, stagers, and others who have attempted to defraud insurance companies. These cases range in size and scope from successful $100,000,000 actions against organized crime rings, to successful single false claim actions against individuals. The approach includes bringing Declaratory Relief Actions, where appropriate, to resolve coverage uncertainties. 9 Page HARMONIE HONORS SUBMISSION
10 ATTORNEY HONOR PAGES (ORANGE COUNTY) Scott Wm. Davenport Scott Wm. Davenport is the head of the firm s Appellate Practice Group. A Certified Specialist in Appellate Law, Mr. Davenport has served as the Chair of the California State Bar Committee of Bar Examiners and the Appellate Law Advisory Commission. He is an AV-Rated attorney and was selected by Los Angeles Magazine as a "Super Lawyer," one of Southern California s Top Lawyers for 6 of the last 8 years. Throughout this career, Mr. Davenport has served as the lead counsel in approximately 400 appellate matters, many of which resulted in published opinions involving cases of first impression, including a per curiam summary reversal in the United States Supreme Court. He has also written multiple amicus briefs on behalf of the Southern Poverty Law Center, a national organization known for its civil rights victories and tolerance education programs. In addition to currently serving as an Appellate Settlement Officer with the Second District Court of Appeals, Mr. Davenport has served as a judge pro tem in the San Bernardino Superior Court. particular. Mr. Davenport recently co-authored a book for the Continuing Education of the Bar on the proper use of scientific evidence, is a regular contributor to the Los Angeles Daily Journal and has recently been featured in the State Bar s Ad Campaign, What Kind of Lawyer Becomes a Certified Specialist? He also served as a legal consultant on the CBS television series The Guardian, an activity which resulted in the drafting of a recurring character for the program named Scott Davenport. In 2006, Mr. Davenport was involved in three United States Supreme Court matters and one matter before the California Supreme Court. In 2007, Mr. Davenport was back in front of the High Court, this time obtaining a summary reversal in Rettele v. County of Los Angeles. From 2008 to 2010, Mr. Davenport filed multiple briefs in the California Supreme Court in the Marriage Cases, as well as an Amicus Curiae brief in the Ninth Circuit Court of Appeals in the subsequent constitutional challenge to Proposition 8. Prior to joining the firm, Mr. Davenport served as a Deputy Attorney General with the California Department of Justice and as a judicial extern with both the California Court of Appeal and the United States District Court. Based on this background, Mr. Davenport is often called upon to defend the State of California and the California Department of Corrections and Rehabilitation in extraordinary writ petitions venued in the variety of trial and appellate courts throughout the state. Mr. Davenport is also a licensed real estate broker who provides practical advice to the firm s real estate clients. In 2011, Mr. Davenport authored a book on Workers Compensation Appeals. He is also slated to present on the topic of workers compensation appeals at an attorney convention in December with Joseph Miller, the Chairman of the Workers Compensation Appeals Board (the equivalent of the Chief Justice of the WCAB). 10 Page HARMONIE HONORS SUBMISSION
11 Lawrence D. Esten Lawrence D. Esten is a partner of the firm's Orange County office. Mr. Esten holds an AV rating (the highest rating available) for his "exceptional legal abilities and professional ethics beyond question," given by the prestigious legal publication Martindale-Hubbell. He has also been recognized as one of California's most outstanding lawyers by Law & Politics, based upon a blue ribbon panel peer review. He was also elected as a member of the distinguished American Board of Trial Advocates (ABOTA), an award only bestowed upon proven trial attorneys. Mr. Esten graduated from Loyola Law School (JD 1986) and from the University of California, Irvine (BA 1983). After law school, he began his legal career as a deputy district attorney in Contra Costa County. After nearly three years as a prosecutor, Mr. Esten went into private practice as a civil litigator. With over 35 jury trials to his credit, he is often called upon by clients and others active in the field to lecture and advise on the issue of defense against fraudulent claims. With his prosecutorial skills and litigation background, he is able to investigate suspect automobile, commercial, and homeowner claims and conduct effective Examinations Under Oath. Mr. Esten volunteers each month to hear Small Claims and Traffic Matters for the Orange County Superior Court. He has completed the CRC and CRC training and continuing education requirements mandated by the State of California for Temporary Judges. He previously served as a reserve police officer in Northern California and was selected by a grand jury panel to serve as a special representative of the Third Supervisorial District in Orange County on the Measure M Citizens Oversight Committee. Mr. Esten also serves on UC Irvine's Athletic Fund Board of Directors. As a licensed California Real Estate Broker, Mr. Esten has considerable experience representing real estate industry professionals, including real estate brokers, loan brokers, appraisers, home inspectors, escrow companies, and title companies. Mr. Esten serves as Chairman of the Real Estate Committee for the Professional Liability Defense Federation.. With more than twenty years of experience as a trial lawyer, Mr. Esten's practice includes all aspects of civil litigation, with an emphasis on the defense of automobile and premises liability matters and professional liability defense of real estate agents and brokers. 11 Page HARMONIE HONORS SUBMISSION
12 ATTORNEY HONOR PAGES (SAN DIEGO) Marguerite Lieu Jonak Marguerite Lieu Jonak is a partner in the San Diego office of Manning & Kass, Ellrod, Ramirez, Trester LLP. Ms. Jonak joined the firm in 1995 after success in numerous jury trials, grand jury proceedings, and investigations at the Los Angeles District Attorney's Office. While assigned to the Insurance Fraud Division, Ms. Jonak became a key member of the team investigating and prosecuting prolific medical-legal provider Dr. Mark Kaplan and his co-conspirators for workers' compensation fraud. The convictions resulted in a prison sentence and the forfeiture of Dr. Kaplan's $7.5 million in assets. Ms. Jonak obtained her Bachelor of Arts degree from the University of Washington in 1986, and her Juris Doctor from Pepperdine University School of Law in Ms. Jonak is certified by the California State Bar as a Specialist in Workers' Compensation Law. Her practice consists of the defense of fraudulent and complex workers' compensation claims. In addition, she represents and counsels employers and businesses on employment and labor issues, contract negotiation, general liability, and other aspects of risk management. Ms. Jonak is the firm's liaison as well as Secretary and Board Member for The Harmonie Group, a global network of law firms which provides on-call emergency services, deep resources on current relevant legal issues, and access to excellence nationwide which is exemplified by Manning & Kass, Ellrod, Ramirez, Trester, LLP. Ms. Jonak is the co-chair of the Workers' Compensation Section of the San Diego County Bar Association, and also serves on the Judicial Election Evaluation Committee. She continues to serve her community as Board Member of Pan Asian Lawyers of San Diego. John D. Marino John D. Marino, a partner in the San Diego office, was born in Los Angeles, California, on August 16, He was admitted to the California Bar in Mr. Marino graduated from the University of California, Irvine (BA 1983) and the University of San Diego School of Law (JD 1986). Mr. Marino is a member of the State Bar of California, the San Diego County Bar Association, the Association of Southern California Defense Counsel, the San Diego Defense Lawyers Association, and the American Inns of Court. He holds a AV rating from Martindale-Hubbell and serves as Judge Pro Tem in the San Diego Municipal Court. Mr. Marino is a member of ABOTA, an invitation-only organization consisting of members that must have at least five years of active experience as trial lawyers, have tried at least 10 civil jury trials to conclusion and possess additional litigation experience, and exhibit the virtues of civility, integrity and professionalism. 12 Page HARMONIE HONORS SUBMISSION
13 His areas of concentration include professional liability (particularly the defense of architects, engineers, and accountants), construction defect, personal injury, and insurance litigation. In addition, he has authored articles for Builder and Developer Magazine. 13 Page HARMONIE HONORS SUBMISSION
14 ATTORNEY HONOR PAGES (SAN FRANCISCO) R. Adam Ellison R. Adam Ellison is a partner in the San Francisco Office of Manning & Kass, Ellrod, Ramirez, Trester LLP. His practice consists of defense of insurance companies, adjusting agencies, third party administrators and employers in all aspects of workers compensation claims. Mr. Ellison has successfully represented his clients at every stage of litigation, including trials, expedited hearings, mediations and expert depositions. He frequently represents employers in Labor Code Section 132a discrimination and serious willful misconduct cases. Among other successful trial results, Mr. Ellison successfully defended a multi-million dollar death case at trial and at the appellate level. He has handled an extensive number of medical lien cases and has prevailed with take nothing verdicts at trial. In an advisory capacity, he also facilitates global settlement negotiations between clients and medical corporations. Mr. Ellison has published articles on current topics and changes in the law including the Almaraz/Guzman and Ogilvie decisions. He is active in organizing comprehensive claim reviews with clients to promote a collaborative approach to claim handling and resolution. In addition, he regularly conducts presentations on a variety of topics, including legal updates, AMA Guides Rating and complex claims management. His work has garnered him recognition as a "Northern California Rising Star" by Law & Politics and San Francisco Magazine for 2008, 2009, 2010, This distinction is limited to only 2.5% of attorneys in the state of California. Mr. Ellison obtained his Bachelor of Arts degree in Political Science and Religious Studies from the University of Vermont in 1998, where he was a member of the mens varsity soccer team. In 2001, he earned his Juris Doctor from Loyola University School of Law in New Orleans. While in law school, Mr. Ellison clerked for the Federal Public Defender Office for the Eastern District of Louisiana and the State of Louisiana's Attorney General's Office. D. Hiep Truong D. Hiep Truong is a partner at Manning & Kass. He is a graduate of the University of California at Berkeley, where he earned a double major Bachelor of Arts degree in the area of Psychology and Sociology in Mr. Truong received his law degree from Santa Clara University School of Law in Mr. Truong is admitted to practice in the United States Supreme Court, United States District Court for the Northern District of California and the Ninth Circuit of the United States Court of Appeals. He has assisted and counseled California Employers on conformance with employment and labor laws during litigation. Just as importantly, he has helped numerous employers avoid litigation. 14 Page HARMONIE HONORS SUBMISSION
15 At Manning & Kass, he continues to serve the interests of California Employers, both large and small. While in law school, Mr. Truong authored numerous articles, which have been published in various national law journals. Some of his writings include: "Daubert and Judicial Review: How Does An Administrative Agency Distinguish Valid Science from Junk Science?" (Published in the University of Akron Law Review); "Encouraging Foreign Direct Investment in Vietnam: Economic Reform, Protection Against Expropriation, and International Arbitration." (Published in the Journal of Transnational Law and Policy; Volume 8:1); and the "Illegal Immigration Reform and Responsibility Act of 1996: A Cost-Effective Measure for U.S. Citizens Or A Punishment for Immigrants Seeking the American Dream? (Published in the DePaul Digest of International Law; Vol. 3; Spring 1997)." All of these articles can be found on-line at Westlaw and Lexis-Nexis. During Mr. Truong's first year of law school, he clerked as an extern in the chambers of the Hon. A. Andrew Hauk, a Federal District Judge in the Central District of California. Mr. Truong was responsible for researching and writing the dispositive motions for the Monday Calendar. During Mr. Truong's second and third year at law school, he worked for the Office of the United States Attorney's Office both in the Eastern and Northern District of California. At the U.S. Attorney's Office in the Eastern District, he worked on the appeal of a complex insurance fraud pyramid scheme. At the U.S. Attorney's Office in the Northern District, he worked on the federal prosecution of a criminal copyright/trade secrets case involving a Fortune 500 Silicon Valley company. After law school, Mr. Truong was a Certified Law Clerk in the Los Angeles County District Attorney's Office, where he conducted preliminary hearings before the Court. Mr. Truong has also engaged in pro bono work. He is a panel member of attorneys at the Electronic Frontier Foundation, and has provided consultation on various areas of intellectual property law. He is also a volunteer Moot Court judge at Stanford Law School (2002 to 2009) and University of San Francisco School of Law (2007 to 2009). He currently volunteers as a Moot Court Judge at University of California, Berkeley s Boalt Hall School of Law and volunteered as a moot court judge for Santa Clara University School of Law in He has also volunteered as a Scholarship Committee Member for the Incentives and Awards Program (IAP) at the University of California at Berkeley. IAP's mission statement is as follows: "The Incentive Awards Program (IAP) provides a $32,000 scholarship award, and student support services to low-income students who have demonstrated leadership potential, high academics, and a commitment to serve others. IAP reaches out to first-generation college students who have overcome great socioeconomic disadvantages through its partnerships with 49 Northern California high schools, and 22 Los Angeles high schools through its Pre-Collegiate Academy." He has also volunteered as an Alumni of the Regents' & Chancellor's Scholars Association (RCSA) at UC Berkeley, where he has provided guidance to current UCB RCSA students regarding a career in law. At SCU, he was a recipient of the B.T Collins Public 15 Page HARMONIE HONORS SUBMISSION
16 Interest Scholarship, California Bar Foundation Scholarship, and the American Jurisprudence/Witkin Award for Academic Excellence in Administrative Law. At Manning &Kass, Ellrod, Ramirez, Trester LLP, Mr. Truong has successfully arbitrated and mediated several cases. His achievements garnered him recognition as a California Rising Star by Law & Politics and Los Angeles Magazine in 2009, 2010, and a distinction limited to only 2.5 percent of attorneys in California. When not in the office, Mr. Truong enjoys running, motorcycle riding (Honda RC-51), playing tennis, photography, and writing. As a Cal Bear Backer, he has season football tickets in the QQ section at Memorial Stadium. He can also be found on the ground after falling off his mountain bike on a quiet, secluded hillside. 16 Page HARMONIE HONORS SUBMISSION
17 ATTORNEY HONOR PAGES (SCOTTSDALE) Robert B. Zelms Robert B. Zelms is managing partner of the Scottsdale office of Manning & Kass, Ellrod, Ramirez, Trester, LLP. Mr. Zelms received his Bachelor of Arts degree in Political Science from the University of Arizona in 1993, and his Juris Doctor from Arizona State University College of Law in 1997, where he was very active in trial advocacy and skills competitions. Mr. Zelms practices primarily in the areas of Professional Liability Defense Litigation, Real Estate Errors & Omissions, Lawyers Professional Liability, Miscellaneous Professional Liability, Construction Defect, Architects & Engineers, Financial Services E&O, Directors & Officers, General Liability, Premises Liability, General Real Estate Litigation, Complex Commercial Litigation, and Insurance Agent E&O. He is an author and editor of Manning & Kass' Arizona Professional Liability, Arizona Real Estate, California/Arizona Legal Malpractice, and Arizona Premises Liability Newsletters. He has completed more than 20 jury trials in the State of Arizona. Mr. Zelms' high profile cases include: Obtained a dismissal for one of Arizona's largest commercial real estate development companies in a Breach of Fiduciary duty claim related to Arizona's stigmatized property statute. Obtained a dismissal for one of Arizona's largest commercial real estate brokerages in a multi-million dollar lawsuit for Breach of Fiduciary duty related to the sale of an apartment complex. Obtained a dismissal for a relocation company in a $7Million Professional Negligence claim arising out of municipal eminent domain action. Defended a Legal Malpractice action arising out of a $22 Million claim related to formation of a charitable tax structure. Obtained a dismissal for one of the largest real estate appraisal groups in the Western U.S. in a multi-million dollar lawsuit brought by a large national lending institution. Successfully defended a concrete company in a $14M construction defect claim arising out of a large master planned subdivision in Arizona. Successfully defended various retail, restaurant, and Fortune 500 companies in tort/premises liability lawsuits throughout the State of Arizona. Mr. Zelms is admitted to the State Bar of Arizona and the U.S. District Court, District of Arizona. He is also a member of the American Bar Association, Defense Research Institute, and LawForKids.org, which provides an online legal Q&A forum for Arizona's school children. Mr. Zelms is a former Chairman of the Southwest Chapter of PLUS (Professional Liability Underwriting Society). In his capacity as Chairman, he was responsible for coordinating the 2009 PLUS-SW Chapter's annual educational event, titled "Market Conditions for 2010," as well as the 2010 annual education event, titled "Navigating the Soft Market." 17 Page HARMONIE HONORS SUBMISSION
18 Mr. Zelms is frequently retained by insurance carriers and brokers to conduct Risk Management Audits and Peer Review Assessments of Attorneys and Law Firms related to E&O insurance renewals. Additionally, Mr. Zelms is an Instructor for the Arizona Association of REALTORS rcrms Risk Management Certification Program. Mr. Zelms is also a frequent lecturer on risk management/claims issues and has conducted seminars for numerous insurance carriers and companies nationwide. Debora L. Verdier Debora L. Verdier is a partner in the Scottsdale office of Manning & Kass, Ellrod, Ramirez, Trester LLP. Ms. Verdier graduated from the Sandra Day O Connor College of Law at Arizona State University in Ms. Verdier defends employers in all types of labor and employment disputes pending before the Equal Employment Opportunity Commission, state and federal courts, and private arbitrators. She has experience in defending employers, including municipalities, against claims of discrimination, harassment, and retaliation brought under Title VII, the Family Medical Leave Act, the Americans with Disabilities Act, the Age Discrimination in Employment Act, and the whistleblower provisions of the American Recovery and Reinvestment Act. Ms. Verdier also has significant experience in handling large and complex litigation matters in the areas of antitrust, copyright, and healthcare reimbursement. She has also litigated disputes associated with the dissolution of businesses or disputes among existing business partners, including claims of breach of contract, mismanagement, fraudulent misrepresentation, and breach of fiduciary and statutory duties. In addition to representing business clients in litigation, Ms. Verdier counsels companies with an eye toward preventing disputes and providing pre-litigation solutions. Ms. Verdier has represented businesses in liability and insurance matters and has represented insurance companies in matters involving reimbursement issues and insurance coverage disputes. Her work in this area has included preparing insurance coverage opinions, reservation of rights letters, and, if necessary, litigating coverage disputes and negotiating resolutions. Ms. Verdier was pleased to be included in the list of Top Lawyers in the Labor and Employment Category in the AZ Business magazine (March/April 2011 and March/April 2013). Ms. Verdier has also been named by Super Lawyers Magazine to the Annual List of Top Attorneys in Arizona and New Mexico (Super Lawyers/Southwest) for In 2012, Ms. Verdier was appointed to the International Association of Defense Counsel. Membership to the 2,500-member group is by invitation only. The International Association of Defense Counsel takes a leadership role in many areas of legal reform and professional development. Ms. Verdier currently serves as a Judge Pro Tem in the Maricopa County Superior Court. She is also an adjunct professor at the Sandra Day O Connor College of Law at 18 Page HARMONIE HONORS SUBMISSION
19 Arizona State University where she teaches a practical skill course called The Litigation Experience. 19 Page HARMONIE HONORS SUBMISSION
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text:
Inhibition by curcumin of multiple sites of the transforming growth factor-beta1 signalling pathway ameliorates the progression of liver fibrosis induced by carbon tetrachloride in rats
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At present there is no effective and accepted therapy for hepatic fibrosis. Transforming growth factor (TGF)-β1 signaling pathway contributes greatly to hepatic fibrosis. Reducing TGF-β synthesis or inhibiting components of its complex signaling pathway represent important therapeutic targets. The aim of the study was to investigate the effect of curcumin on liver fibrosis and whether curcumin attenuates the TGF-β1 signaling pathway.
Sprague–Dawley rat was induced liver fibrosis by carbon tetrachloride (CCl4) for six weeks together with or without curcumin, and hepatic histopathology and collagen content were employed to quantify liver necro-inflammation and fibrosis. Moreover, the mRNA and protein expression levels of TGF-β1, Smad2, phosphorylated Smad2, Smad3, Smad7 and connective tissue growth factor (CTGF) were determined by quantitative real time-PCR, Western blot, or immunohistochemistry.
Rats treated with curcumin improved liver necro-inflammation, and reduced liver fibrosis in association with decreased α-smooth muscle actin expression, and decreased collagen deposition. Furthermore, curcumin significantly attenuated expressions of TGFβ1, Smad2, phosphorylated Smad2, Smad3, and CTGF and induced expression of the Smad7.
Curcumin significantly attenuated the severity of CCl4-induced liver inflammation and fibrosis through inhibition of TGF-β1/Smad signalling pathway and CTGF expression. These data suggest that curcumin might be an effective antifibrotic drug in the prevention of liver disease progression.
Liver fibrosis and its end stage, cirrhosis, represent the final common pathways of virtually all chronic liver diseases
Current evidence suggests that the process of hepatic fibrosis is driven by a complex network of cytokines, foremost being transforming growth factor (TGF)-β1 and connective tissue growth factor (CTGF)
TGF-β1 acts through different signalling pathways, the most important being the canonical Smad pathway
CTGF, also known as CCN family 2 (CCN2), is induced by TGF-β and is considered a downstream mediator of the effects of TGF-β on fibroblasts
Curcumin, a polyphenol (diferuloylmethane), is the main active compound found in the perennial plant
Carbon tetrachloride (CCl4) and curcumin were purchased from Sigma Chemical Co., Ltd. (St. Louis, MO) and dissolved in olive oil and PBS, respectively, for experiments in animals. Antibodies included human polyclonal anti-TGF-β1 antibody (Promega, Madison, WI), rabbit anti-TGF-β1 polyclonal antibody (Boster Co., Ltd., Wuhan, China), goat polyclonal anti-CTGF antibody (Santa Cruz Biotechnology, Santa Cruz, CA), rabbit monoclonal anti-Smad2, anti-Smad3 and anti-Smad7 antibodies (Epitomics, Burlingame, CA), rabbit polyclonal anti-phospho-Smad2 (
Animals and experimental protocols
Male Sprague–Dawley rats weighing 180–220 g were obtained from the animal centre of Fudan University (Shanghai, China) and maintained in an environmentally controlled room (23 ± 2°C, 55 ± 10% humidity) with a 12-hour light/dark cycle and free access to food and water. Liver fibrosis was induced by administration of 2 ml of CCl4/olive oil (1:1, v/v)/kg body weight by intraperitoneal (i.p.) injection twice weekly for up to 6 weeks. Fifty rats were randomly divided into four groups. Rats in group 1 (n = 10) received twice weekly injections of olive oil (vehicle control). Rats in group 2 (n = 10) were injected with olive oil, as in group 1, and received oral curcumin (200 mg/kg)
Histopathological evaluation
Harvested liver tissues were fixed in 10% neutral buffered formalin and embedded in paraffin. Slices 4 μm thick were prepared and stained with haematoxylin and eosin and Sirius red according to standard procedures. Liver necroinflammatory activity was evaluated semiquantitatively according to the METAVIR scoring system
Immunohistochemical evaluation
Liver tissue sections were dewaxed, hydrated and subjected to heat-induced antigen retrieval. Sections were blocked and incubated overnight at 4°C with (1) rabbit anti-TGF-β1 polyclonal antibody (1:50), (2) anti-Smad2 antibody (1:50), (3) anti-Smad3 antibody (1:100), (4) anti-CTGF antibody (1:100) and (5) anti-α-SMA antibody (1:100), with all antibodies diluted in TBS–2% bovine serum albumin. Negative-control antibodies were species-matched and, where appropriate, immunoglobulin G subclass-matched Ig fractions. The sections were washed and incubated with secondary antibodies. Colour was developed by incubation for 5–10 min with 3, 3′-diaminobenzidine tetrachloride, and specific staining was visualized by light microscopy.
Western blot analysis
Liver samples were homogenized and centrifuged at 10,000
Real-time quantitative RT-PCR
Total RNA was extracted from frozen liver tissues using Trizol reagent according to the manufacturer's protocol (Life Technologies, Grand Island, NY). RNA extracts were reverse-transcribed with random hexamers and avian myeloblastosis virus reverse transcriptase using a commercial kit (Perfect Real Time, SYBR® PrimeScriP™ TaKaRa, Shiga, Japan). Real-time RT-PCR for quantitative assessment of mRNA expression was performed on an ABI Prism 7000 Sequence Detection system (Applied Biosystems, Tokyo, Japan) according to the manufacturer's protocol. Probes and primers for TGF-β1, CTGF, Smad2, Smad3, Smad7, and GAPDH (Table
Statistical analysis
All statistical analyses were performed using SPSS statistical software (SPSS for windows, version 15.0). All data are presented as mean ± SD. Differences in measured parameters among groups were analysed by one-way analysis of variance followed by the Tukey test when F was significant. Differences were considered significant at p values less than 0.05.
Curcumin administration ameliorates hepatic injury, inflammation and fibrosis in liver tissue of CCl4 treated rats
No rats died in group1 and group2 during the 6 weeks of experimental period, while 4 and 5 rats died in group 3 (Curcumin/CCl4) and group 4 (PBS/CCl4), respectively. The ability of curcumin to protect rat livers against injury and fibrogenesis induced by CCl4 was evaluated histologically (Figure
Figure 1
Curcumin (Cur) administration ameliorates hepatic inflammation and fibrosis induced by CCl4 administration
Curcumin (Cur) administration ameliorates hepatic inflammation and fibrosis induced by CCl4administration. (A) Haematoxylin and eosin (H&E) staining of the livers (original magnification, ×200). (B) Evaluation of liver fibrosis by Sirius red staining of liver sections (original magnification, ×200). (C) Semiquantitative evaluation of liver necro-inflammatory activity according to the METAVIR scoring system.
Prolonged CCl4 treatment induced the formation of necrotic areas in rat livers, with considerable infiltration of inflammatory cells into areas surrounding the centrilobular veins (Figure
Curcumin inhibits hepatic fibrogenesis and activation of hepatic stellate cells in liver tissue of CCl4 treated rats
To assess the impact of curcumin on CCl4-induced hepatic fibrogenesis, liver sections were stained with Sirius red to detect the deposition of collagens. Rats receiving CCl4 for 6 weeks developed significant fibrosis, with initial stages showing the characteristic patterns of perivenular and periportal deposition of connective tissue, along with the development of thin portal-to-portal septa and slight evidence of architectural distortion resulting in micronodular fibrosis (Figure
HSC proliferation has been reported augmented when these cells were cultured on type I collagen, the predominant matrix component increased in liver fibrosis. We therefore analysed the effect of curcumin on the expression of type I collagen protein. We found that, compared with control rats, CCl4-treatment resulted in marked collagen-I accumulation in the liver, with increased collagen-I expression in the periportal areas and areas of bridging fibrosis in the liver, as shown by immunohistochemistry (Figure
Figure 2
Effects of curcumin on activation of hepatic stellate cells (HSCs) and collagen type I protein expression in the liver
Effects of curcumin on activation of hepatic stellate cells (HSCs) and collagen type I protein expression in the liver. (A, B) Immunohistochemical staining of type I collagen and alpha-smooth muscle actin (α-SMA) in the liver (original magnification, ×200). (C, D) Western blotting analysis of hepatic collagen-I and α-SMA expression. Liver tissue was lysed and subjected to western blot analysis for collagen-I and α-SMA, and the loading control GAPDH. Blots obtained from several experiments were analysed using densitometry, and the densitometric values were pooled from four animals per group and shown as means ± SD in the bar graph. *
Activated HSCs, which expression myogenic markers such as α-SMA, are considered central ECM-producing cells within the injured liver
Curcumin administration inhibits hepatic TGF-β1 expression in liver tissue from CCl4 injected rats
Since the multifunctional cytokine TGF-β1 has been found to play important roles in the development of liver diseases
Figure 3
Effects of curcumin (Cur) on transforming growth factor beta1 (TGF-β1) expression in the liver
Effects of curcumin (Cur) on transforming growth factor beta1 (TGF-β1) expression in the liver. (A) Immunohistochemical assessment of TGF-β1 in the liver (original magnification, ×200). (B) Western blotting analysis of hepatic TGF-β1 expression. Liver tissue was lysed and subjected to western blot analysis for TGF-β1, and the loading control GAPDH. Blots obtained from several experiments were analysed using densitometry, and the densitometric values were pooled from four animals per group and are shown as means ± SD in the bar graph. *
Using quantitative real-time PCR, we assayed the intrahepatic expression of TGF-β1 mRNA 6 weeks after CCl4 injection, with or without curcumin treatment. We found that CCl4 markedly increased intrahepatic TGF-β1 mRNA levels, but this increase was attenuated in rats that received oral curcumin (Figure
Curcumin induces Smad7 and inhibits Smad2, P-Smad2 and Smad3 expression in liver tissue of CCl4 treated rats
TGF-β1 signals are mediated by Smad. Following ligand binding to TGF-β type II receptors (TβRII), TGF-β type I receptors (TβRI) are activated and bind Smad2 and Smad3 proteins. These proteins are subsequently phosphorylated, forming an oligomeric complex with Smad4
We found that Smad2 and Smad3 were expressed in the cytoplasm, but not the nuclei, of liver cells in all groups of rats (Figure
Figure 4
Effects of curcumin (Cur) on the expression of Smad2 and Smad3 proteins in rat liver tissue
Effects of curcumin (Cur) on the expression of Smad2 and Smad3 proteins in rat liver tissue. (A, B) Immunohistochemical staining for Smad2 and Smad3 in the liver (original magnification, ×200). (C, D) Western blot analysis of hepatic Smad2 and Smad3 expression. Liver tissue was lysed and subjected to western blot analysis for Smad2 and Smad3 and the loading control GAPDH. Blots obtained from several experiments were analysed using densitometry, and the densitometric values were pooled from four animals per group and shown as means ± SD in the bar graph. *
Western blotting experiments showed that Smad2 (Figure
Figure 5
Curcumin induces Smad7 and inhibits Smad2, P-Smad2, and Smad3 mRNA and protein expression in liver tissue of CCl4 injected rats
Curcumin induces Smad7 and inhibits Smad2, P-Smad2, and Smad3 mRNA and protein expression in liver tissue of CCl4injected rats. (A-C) The levels of Smad2 (A), Smad3 (B) and Smad7 (C) mRNA in liver tissue were determined by quantitative real-time RT-PCR. Smad2, Smad3 and Smad7 mRNA levels were normalized relative to GAPDH mRNA expression in each sample, and values are expressed as the mean ± SD fold increase over normal control group (n=6).
We also assayed the intrahepatic expression of Smad2, Smad3 and Smad7 mRNAs by quantitative real-time PCR. We found that CCl4 administration for 6 weeks markedly enhanced intrahepatic Smad2 and Smad3 mRNA expression, but that this was attenuated in rats also administered curcumin (Figure
Curcumin inhibits CTGF expression in liver tissue of CCl4 treated rats
To assess the location and dynamics of CTGF expression in liver fibrosis, we immunohistochemically analysed the expression of CTGF protein in rats treated with CCl4 for 6 weeks. We found that CTGF was strongly expressed in these livers, with CTGF localizing along the fibrous septa and in different types of liver cells, including HSCs and hepatocytes (Figure
Figure 6
Curcumin inhibits connective tissue growth factor (CTGF) expression in liver tissue of CCl4 treated rats
Curcumin inhibits connective tissue growth factor (CTGF) expression in liver tissue of CCl4treated rats. (A) Immunohistochemical staining for CTGF in rat liver (original magnification, ×200). (B) Western blots analysis of hepatic CTGF expression and GAPDH as loading control. Blots obtained from several experiments were analysed using densitometry, and the densitometric values were pooled from four animals per group and are shown as means ± SD in the bar graph. *
When we assayed intrahepatic CTGF mRNA by quantitative real-time PCR, we found that CCl4 enhanced intrahepatic CTGF mRNA levels, whereas curcumin attenuated this increase (Figure
Liver fibrosis is an outcome of many chronic diseases and often results in cirrhosis. Cirrhosis has been associated with significant and life-threatening complications, including liver failure, portal hypertension and hepatocellular carcinoma, and represents a major cause of morbidity and mortality worldwide
We have shown here that prevention with curcumin (200 mg/kg) significantly attenuated the progression of hepatic fibrosis in rats induced by CCl4 injection. Curcumin not only reduced the severity of liver necro-inflammation, but significantly suppressed the activation of HSCs and reduced collagen accumulation and the expression of type I collagen protein. These changes were accompanied by the down-regulation of TGF-β1/Smad signalling and CTGF expression in the livers of rats with hepatic fibrosis.
Curcumin (diferuloylmethane) is an active phenolic compound extracted from the rhizome of the plant
Fibrosis develops as a result of the sustained wound-healing processes that occur in the liver in response to chronic injuries and inflammation. Chronic and repeated hepatic inflammation has been found to result in hepatic fibrosis and cirrhosis
It is well known that inflammation is an important element in the initiation and progression of liver fibrosis
TGF-β signals through transmembrane receptors that stimulate cytoplasmic Smad proteins, which in turn modulate the transcription of target genes, including those encoding ECM components, such as procollagen-I and -III
In contrast, Smad7 blocks R-Smad phosphorylation and subsequent downstream events by forming a stable complex with activated TβRI
CTGF is a member of the CCN family of proteins and plays a pivotal role in fibrosis of the lungs, skin, kidneys, and heart by affecting ECM production, cell cycle control, and cell adhesion and migration
Although the main source of CTGF was thought to be HSCs and fibroblasts, recent reports have revealed that hepatocytes also produce CTGF
Our findings demonstrate that early and chronic administration of curcumin effectively protected rat livers from CCl4-induced liver injury and fibrogenesis. These beneficial effects of curcumin, delaying the progression of hepatic fibrosis, involved inhibiting the TGFβ1/Smad signalling pathway and decreasing CTGF expression. Our results suggest that curcumin may be useful for prevention of hepatic fibrosis in patients with advanced liver disease.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
QYY and BLX carried out the study and designed the experiments. QYY, HCL, and CTT contributed reagents, materials, analysis tools, and interpretation of data. QYY, HCL, and BLX contributed animal model. JYW and SCZ analyzed data, helped conceive the study, and participated in its design. CTT conceived and designed experiments and wrote the manuscript. All authors read and approved the final manuscript.
This work was partially supported by the National Natural Science Foundation of China, grant number 81170398.
Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ
Mechanisms of hepatic fibrogenesis
TGF-beta signaling and the fibrotic response
Mechanisms of hepatic fibrogenesis
Liver fibrosis
Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-beta as major players and therapeutic targets
Mechanisms of TGF-beta signaling from cell membrane to the nucleus
Smad3: a key player in pathogenetic mechanisms dependent on TGF-beta
Anti-fibrogenic strategies and the regression of fibrosis
Connective tissue growth factor: a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10
CTGF and SMADs, maintenance of scleroderma phenotype is independent of SMAD signaling
Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets
Role and interaction of connective tissue growth factor with transforming growth factor-beta in persistent fibrosis: A mouse fibrosis model
Connective tissue growth factor: a mediator of TGF-beta action on fibroblasts
Connective tissue growth factor: a fibrogenic master switch in fibrotic liver diseases
Profibrogenic transforming growth factor-beta/activin receptor-like kinase 5 signaling via connective tissue growth factor expression in hepatocytes
Differential effects of TGF-beta on connective tissue growth factor (CTGF/CCN2) expression in hepatic stellate cells and hepatocytes
Inhibition of connective tissue growth factor by siRNA prevents liver fibrosis in rats
Pharmacological actions of curcumin in liver diseases or damage
Curcumin protects mice against concanavalin A-induced hepatitis by inhibiting intrahepatic intercellular adhesion molecule-1(ICAM-1) and CXCL10 expression
Molecular understanding and modern application of traditional medicines: triumphs and trials
Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases
Curcumin protects the rat liver from CCl4-caused injury and fibrogenesis by attenuating oxidative stress and suppressing inflammation
Prevention of liver cirrhosis in rats by curcumin
A polymeric nanoparticle formulation of curcumin (NanoCurc™) ameliorates CCl4-induced hepatic injury and fibrosis through reduction of pro-inflammatory cytokines and stellate cell activation
An algorithm for the grading of activity in chronic hepatitis C
Antifibrotic activity of rofecoxib in vivo is associated with reduced portal hypertension in rats with carbon tetrachloride-induced liver injury
Increases in p53 expression induce CTGF synthesis by mouse and human hepatocytes and result in liver fibrosis in mice
Evolving challenges in hepatic fibrosis
Multi-targeted therapy by curcumin: how spicy is it?
Perspectives on chemopreventive and therapeutic potential of curcumin analogs in medicinal chemistry
Curcumin prevents and reverses cirrhosis induced by bile duct obstruction or CCl4 in rats: role of TGF-beta modulation and oxidative stress
Curcumin blocks multiple sites of the TGF-beta signaling cascade in renal cells
Transforming growth factor beta and the liver
TGF-β in progression of liver disease
The role of Smad3 in mediating mouse hepatic stellate cell activation
Targeted disruption of Smad3 confers resistance to the development of dimethylnitrosamine-induced hepatic fibrosis in mice
Curcumin inhibits transforming growth factor-beta activity via inhibition of Smad signaling in HK-2 cells
siRNA-mediated knockdown of connective tissue growth factor prevents N-nitrosodimethylamine-induced hepatic fibrosis in rats
Curcumin inhibits connective tissue growth factor gene expression in activated hepatic stellate cells in vitro by blocking NF-kappaB and ERK signalling
Curcumin prevents and reverses murine cardiac hypertrophy
IL-13 induces connective tissue growth factor in rat hepatic stellate cells via TGF-β- independent Smad signaling
Evidence for the involvement of TGF-β1-CTGF axis in liver fibrogenesis secondary to hepatic viral infection
Pre-publication history
The pre-publication history for this paper can be accessed here:

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text: Bethesda, June 11, 2013 (GLOBE NEWSWIRE) -- India Globalization Capital, Inc. (NYSE MKT: IGC) announced the achievement of a milestone in the execution of its strategic plan. IGC has completed a test shipment of 300 tons of iron ore from Mongolia to China. As previously reported, the Company established a shipping hub at the border of Mongolia and China to provide iron ore to its customers in China and source raw materials. Ram Mukunda, CEO of IGC, said, "Importing from Mongolia has important strategic value. Our beneficiation plants process low-grade ore into high-grade ore. It has been our plan to diversify the source of raw materials, from India and Mongolia, to include grades of ore that are of substantially better quality than our reserves. This test delivery has been a big step for IGC in delivering on the opportunities before us." Mr. Mukunda spoke of the comparative benefits of IGC's strategy for its anticipated Mongolian reserves. He continued, "On our mine sites in Inner Mongolia, we have reserves that are 2 or 3% Fe content, which is processed into 66% Fe ore using a dry magnetic separation process and a wet magnetic separation process. The 66% high-grade ore is then sold to steel mills. 70 truckloads of raw material are required to produce two truckloads of higher-grade iron using the dry separation process, and the two truckloads of higher-grade ore are subsequently processed through the wet separators to produce the end product of one truckload of 66% high-grade ore. This process is profitable at higher levels of iron ore pricing. But both Mongolian and Indian ore have a base level of 40% to 50% Fe content, and in order to process these for use in steel mills, we employ just the wet separator and thus achieve considerable cost savings in producing the desired product. To illustrate, 1.3 truckloads of this type of ore can be used to produce one truckload of 66% high-grade ore. Overall, this is higher margin production and is profitable even at lower sale prices."


text:
Once you have cleaned a section with the fireplace, you can then get the next piece of material which is the dried up one and start clearing off it and polishing that bit of the fireplace that you have just cleaned with the liquid. You can continue working your way across the fireplace this way as it prevents stains from your liquid.
One of the wide range of options available in the tiles market, travertine mosaic tiles possess a lot of importance. We usually look for specific qualities just like the looks, easy application and sturdiness when choosing the particular tiles for the house. The design carry a large amount of importance since they give the first impression. Each room in the house needs good wealthy looks, which are provided by the travertine mosaic tiles. You can use them inside rooms of all sizes. These normal stones provide a clean and traditional look to the particular interiors of the property. You can also bring about a stylish and trendy look with their different finishes. If you are anyone, who does not like the look of the manufactured floor tiles, and adore the look of natural stones, travertine is the best option. The popularity is to possess environmentally friendly features at home.
When it comes time for a bathroom or kitchen remodel the average consumer needs to pay attention to the type of components being picked and installed. Minimum building codes have established yourself, but remember that «minimum» is the key term. Building requirements were created to create a safe environment for the occupants. The level of quality craftsmanship and many types of materials isn't necessarily specific. There are many situations and materials throughout the home which the constructing codes do not take into account.
Gorgeous and elegant, but at the same time, rugged and durable, nothing can beat natural stone in terms of choice of flooring material. Moreover, compared to other other types of floor coverings that are really heavy on maintenance, taking care of flooring associated with natural stone far less laborious. Along with very little effort, your natural stone flooring can look beauty as well as vibrant since way back when.
Botticino marble tiles have many qualities that will make them not the same as other floors like porcelain, slate and granite. Aside from being beautiful, these foundations are remarkably hard wearing and may withstand scrapes by bulky objects as well as take punishment from the shoes or boots. There is nothing that can break these types of slabs other than hammer. This selection makes them merely perfect for use on stairs, entry and back garden path. When installed, they can last more than the age of your home. These foundations remain unaffected from warm weather, chill heat and even acidic rain water does not have any impact on them. Modern homeowners want peace of mind because they can't devote much time in washing their floor coverings, wall ceramic tiles and counters.
Marble Polishing Products: Another Hobby
Once you have cleaned a section with the fireplace, you can then get the next piece of material which is the dried up one and start clearing off it and polishing that bit of the fireplace that you have just cleaned with the liquid. You can continue working your way across the fireplace this way as it prevents stains from your liquid.
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A Low carb Calculator to find unlisted carbs based on a food products label.
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Should I Keep These?
Discussion in 'Recent Oakley Purchases' started by randsome01, 3/10/14.


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Currie Graham portrayed Calvin Chadwick in the Agent Carter episodes The Lady in the Lake, A View in the Dark, Better Angels, Smoke & Mirrors, The Atomic Job, Life of the Party and Hollywood Ending.
- Currie Graham is one of the actors to portray characters for both Marvel Studios and DC Entertainment. He portrayed Derek Reston/King of the Royal Flush Gang in Arrow.