Researchers are constantly searching for methods to generate models for testing hypotheses within the context of biological relevance. Not only is it important to generate models that are fully functional to test an hypothesis, but these models must mimic that biological system of interest as seen within its natural context. Scientists at the University of Leipzig in Germany are lending their expertise in this emerging area with particular focus on the liver. The liver plays a variety of very pivotal roles in the human body, such as detoxifying drugs and other substances that we ingest,  protein synthesis and fat metabolism.

Primary hepatocytes (liver cells) present an appropriate model for the validation of a system for toxicological studies of new drugs and chemicals that may be used in the pharmaceutical/cosmetics industries and biologically relevant models are needed to test the affects of these chemicals within a biological context. However, there are no models currently available to do this.

Dr. Peggy Stock and her colleagues at the University of Leipzig in Germany are conducting research in generating appropriate models for liver toxicity studies. In preliminary studies presented at the 2012 Experimental Biology Conference in San Diego, California, this group presented data analysing the applicability of using 3D versus 2D collagen-coated silicone scaffolds for models of human liver. This group utilized rat hepatocytes (rat liver cells) as a cellular model for human liver, since rat liver cell processes mimic that of humans to a high degree.

Primary rat hepatocytes were cultured (grown) for 72h on a 3D structure and was compared with 2D culture on conventional cell culturing methods utilizing cell culture dishes. Cell counts and the growth patterns of these cells on silicone and the urea production rate were also determined as urea production takes place in the liver and it can serve as a marker of liver health and function.

Based on identical initial cell counts the growth rate was about 42% higher in 3D culture as compared to 2D. In addition, cells attached to the scaffold and formed clusters and organ-like structures that are native to the liver. The 3D culture on the silicone scaffold displayed no significant signs of toxicity after 3 days of cell culture. The urea production rate, which is a marker of liver health and function, was significantly higher in the 3D vs 2D cell culturing system.

Results from these studies demonstrate the appropriateness of using 3D models for the culture of primary rat hepatocytes. Thus, revealing that these 3D scaffolds may be utilized as an important tool for the development of 3D liver models for understanding and examining liver function within a laboratory setting.

Results of study using animal model among the presentations at the meeting
Experimental Biology 2012

SAN DIEGO— Heart failure is the most common cause of death throughout the world, typically the result of chronic high blood pressure, also known as hypertension. As a result, research efforts have focused on an array of approaches aimed at preventing and treating high blood pressure. Recently, Japanese researchers examined the utility of an anti-hypertensive drug, moxonidine, which acts on the imidazoline receptors in the cardiovascular center of the brainstem. They found, using an animal model, that the drug can improve heart function and survival independent of its effect on blood pressure. They also found the drug had a favorable effect on oxidative stress, which is related to insulin resistance, the underlying abnormality in diabetes, which is common in people with heart failure.

An abstract presentation about the findings will be offered at the meeting Experimental Biology 2012, being held April 21-25 at the San Diego Convention Center. The study was conducted by Yoshitaka Hirooka, Nobuhiro Honda, Ryuichi Matsukawa, Koji Itou and Kenji Sunagawa, all of the Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences in Fukuoka, Japan. It is entitled, “Central sympathoinibition improves left ventricular function during the transition from hypertrophy to heart failure in Dahl salt-sensitive rats.” The abstract is sponsored by the American Society for Investigative Pathology (ASIP), one of six scientific societies sponsoring the conference which last year attracted some 14,000 attendees.

Heart failure is a chronic disease that takes many forms and a variety of medications are used to treat it. Drugs such as ACE inhibitors and beta blockers target the causes of systolic heart failure. Clonidine, a first-generation central sympathoinhibitory drug, targets brain receptors that reduce cardiac output and lower blood pressure. Moxonidine, a second-generation drug, targets diastolic heart failure and function by reducing the effect of the central nervous system (CNS) receptors to decrease sympathetic activation and thus reduce blood pressure. In the study, salt-sensitive, hypertensive rats either received Moxonidine or were assigned to the control group. Researchers later found that the animals who received the drug had a marked inhibition of the sympathetic activity (an area of the brain) compared to those that did not. The findings suggest that inhibition of the central sympathetic outflow is important in the mechanism of hypertension. According to Dr. Hirooka, “The findings are important because they suggest that moxonidine may be useful in targeting the central receptors in the brain that are known to occur in patients with hypertension.”

Next Steps
The study is the latest in a series conducted by the research team whose focus is on neural control of circulation in hypertension and heart failure. Looking ahead, they will work to identify the precise mechanisms involved in the beneficial effect of moxonidine, Dr. Hirooka said. They will also study other ways to see if the compound is a possible therapeutic tool for hypertensive heart disease to prevent heart failure. As the drug had beneficial effects on insulin resistance, they would like to further investigate the issue, he added Maxonidine is available in select countries in Europe and Asia. It is not currently available in the United States.

Adapted from Donna Kupa (dkrupa@the-aps.org)

The American Society for Investigative Pathology will be honoring a plethora of science talent at this year’s Experimental Biology Meeting in San Diego. The reception is scheduled to take place on Monday, April 23, 2012 in the San Diego Convention Center Rm. 16A.  The researchers represent some of the leading scientists in the pathology field and are setting the pace for future trainees.

Awards will be given in several categories ranging from undergraduate research awards to awards for established principle investigators.

Check out the award winners below!

2012 Gold-Headed Cane Award – Federick F. Becker, MD

Rous-Whipple Award – Patricia D’ Amore, PhD

Outstanding Investigator Award – Dr. Kojo Elenitoba-Johnson, MD

2012 ASIP Robbins Distinguished Educator Award – Peter G. Anderson, D.V.M., PhD

2012 Cotran Established Investigator Award – Andrei I. Ivanov, PhD

2012 ASIP Excellence in Science Award – Edward B. Lee, MD, PhD

Let’s not forget our future science leaders!!

ASIP 2012 Trainee Travel Awards

Experimental Pathologist in Training Award – Ronen Sumagin

Postdocotral Merit Award – Michael Schnoor

Experimental Pathologist-in-Graduate Training Award – Jacqueline D. Jones

Predoctoral Merit Awards – Prince Awuah, Duke A. Geem

A.D. Sobel – ASIP Education Fund Scholars – Shijun Wang, David P. Sullivan, Porfirio Nava-Dominguez, Emily D. Wickline, Kristine Wadosky, David Wayne Melton

ASIP Travel Awards – Veronica Azcutia, Ludovic Benard, Kari Nejak-Bowen, Ana C. Monteiro, Maria L. Tomasi, Vanessa Kissoon-Singh, Manirath Khounlotham, Ines Barone, Nayden Gueroguieve Naydenov, Jonathan Proto

Minority Travel Trainee Travel Award – Diana Londono, Rogelio Zamilpa, Angel Byrd, Lantz Mackey, Cindy Thomas-Charles, Evan Delgado, Rodolfo Villareal-Calderon, Olachi Mezu-Ndubuisi, Courtney Johnson, Dylan Heart

 

 

 

 

 

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During this year’s Experimental Biology Conference in San Diego, California, I have the great opportunity of serving as the official meeting blogger for the American Society for Investigative Pathology (ASIP). As a graduate student this presents itself as a wonderful opportunity in not only to attend a great meeting but to blog among the ranks of some of the best science bloggers in the game. Many have reached out to offer their assistance in keeping me up to speed during the process.

I must admit that I am “super” excited and I encourage you all to visit my blog for updates regarding the Experimental Biology Conference and ASIP news. ASIP is only a year away from celebrating its centennial. For almost one-hundred years, this society has focused on science excellence and outreach. Some ASIP highlights will include symposiums ranging from the Molecular and Cellular Basis of Disease (4/22) and a Personalized Medicine and Breast Cancer Workshop (4/21). Additionally, I will be using twitter and I will be tweeting on ASIP’s behalf @SciReflector. A link to my twitter page can be found on the home page of the Science Reflections blog.

May happy blogging speed my way!!

#EB2012