Aktuelles Archiv

[address of welcome]

Contents:
1. WELCOME
2. HIGHLIGHTS OF THE FIRST HALF OF 2010
3. INTERSPECIES DIFFERENCES
4. INTERESTING METHODS
5. LATEST NEWS
6. SELECTED FORTHCOMING DEADLINES
7. CLOSING REMARKS

1. WELCOME

Welcome to our first newsletter in 2010!

In some areas of research you can observe greatest efforts to make a shift of paradigm to non-animal methods. So there is a call for „Making `Alternatives´ the New Gold Standard“ for chemical risk assessment. In his plenary lecture held at 7th World Congress in Rome, reproduced in the actual issue of ALTEX [1], M. E. Andersen declares the 2007 NAS report, Toxicity Testing in the 21st Century – A Vision and a Strategy to be a clear goal which envisions a future where all routine toxicity testing for environmental agents will be conducted in human cells in vitro. He points out that all of the tools necessary for the transformation of toxicity testing to an in vitro platform are either available or in advanced development, and encourages the parties involved, namely the scientific community, animal alternatives groups, regulatory agencies, and funding organizations, „to work together to make this vision a reality“.

Exactly in this notion the project InVitroJobs.com stands as scientific project of „People for Animal Rights Germany“. Amongst others we want to bring together the established well experienced researchers with young scientists and to enlarge existing networks among the established groups by initiating new connections.

First of all we want to start off with a short review about interesting highlights of the first half of 2010, which shows that interdisciplinarity and innovative thinking leads to promising concepts to replace animal experiments and thereby to improve security of consumers. One problem of the use of animal models for humans is the interspecies difference. This topic is investigated by many researchers. Some interesting findings will be presented. As well as some interesting new alternative approaches.

We hope you will enjoy this newsletter and feel free to recommend it to your colleagues!

2. HIGHLIGHTS OF THE FIRST HALF OF 2010

Center for Alternatives to Animal Testing – Europe (CAAT-EU) was founded,
based on collaboration between the Johns Hopkins Bloomberg School of Public Health and the University of Konstanz. CAAT-EU, housed at the University of Konstanz, amongst others will coordinate transatlantic activities to promote humane science in research and education.

In vitro pyrogen test introduced into the European Pharmacopoeia
The test, devised by T. Hartung und A. Wendel, was developed at the University of Konstanz, Germany, and now helps to avoid the suffering of 200.000 rabbits per annum in Europe. S.R.M. Fennrich, head of the developing group from 1997 to 2005, received several awards for the development of the test. The assay now is introduced into the European Pharmacopoeia in 2010.

OECD finally approved skin irritation test without animal experiments
An animal-free method has been included in the test guideline (439 In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method) on July, 22. This method now is approved by the authorities and has world-wide validity. With implementation of this in vitro test the amount of rabbits killed is expected to decrease significantly.
Such test systems are available for many years. OECD allowed testing of irreversible damages of the skin with skin models since 2004. Now, 6 years later, also reversible skin irritations are allowed to be tested with the same alternative methods.

(See more highlights and findings at our News archive:
www.invitrojobs.com)


3. INTERSPECIES DIFFERENCES

Chymases are variably expressed in different species
Chymases are mast cell serine proteinases and chymase inhibitors have emerged as potential therapeutic agents for treating various disorders. J. Kervinen and colleagues, PA/USA, expressed chymases from humans, macaques, dogs, sheep, guinea pigs, and hamsters [2] and evaluated in vitro the potency of nonpeptide inhibitors, originally targeted against human chymase with the result that „the inhibitors exhibited remarkable cross-species variation of sensitivity, with the greatest potency observed against human and macaque chymases“. They argue, that the compounds were „10-300-fold less potent, and in some instances ineffective, against chymases from the other species“.
Link to original article

Evolutionary relationship determines not the grouping of kinetics of methylation of inorganic arsenic
Scientists from North Carolina investigated interspecies differences in the metabolism of inorganic arsenic (iAs) [3] by using cultures of primary hepatocytes from different species, because the liver is considered the primary site for the methylation of iAs. The findings of Drobná et al. show, that dog, rat and monkey hepatocytes were „considerably more efficient methylators“ than mouse, rabbit or human hepatocytes. No associations between the rates of iAs methylation and the protein structures of the key enzyme of the pathway were found for the species examined. The superior arsenic methylation capacities of dog, rat and monkey hepatocytes examined may be associated with a higher expression of the key enzyme. Furthermore the authors show an inhibition of the enzyme by low levels of iAs(III) only in the group of human, rabbit and mouse.
Link to original article

Human cells instead of a porcine cell line to use in in vitro nephrotoxicity studies to predict effects in humans
To study the nephrotoxic effects of drugs in humans a porcine renal proximal tubular cell line is routinely used. Because of „significant interspecies differences in drug pharmacokinetics and pharmacodynamics“, P. Gunness and colleagues investigated [4] whether a human renal proximal tubular cell line HK-2 is an acceptable model to use. Their findings support clinical pathology data in humans, and „suggest that HK-2 cells are a suitable model for use in in vitro toxicity studies to determine drug-induced nephrotoxicity in humans“.
Link to original article

Species-depending effects of induced coronary dilation
Hungarian scientists investigated isolated coronary arteries from human, porcine, and canine hearts [5], to observe the effects of cromakalim, a potassium-channel opening vasodilator, under different conditions of extracellular calcium concentration. The findings of  J. Pataricza and colleagues lead to the conclusion, „that the coronary dilating effect of cromakalim largely depends on the species“ and is modulated by the extracellular calcium concentration with a partly endothelium dependent manner.
Link to original article

Functional data of individual genes from mouse may not apply to human in certain occasions
The Chinese researchers R. Yang and B. Su pointed out [6], „great efforts have characterized many individual genes responsible for the interspecies divergence, yet little is known about the genome-wide divergence at a higher level.“ Modules are serving as the building blocks and operational units of biological systems. They conducted a comparative analysis between species at the module level. The composition of modules exhibits a great difference between human and mouse. The findings imply that „similar biological processes can be carried out by different sets of genes from human and mouse, therefore, the functional data of individual genes from mouse may not apply to human in certain occasions.“
Link to original article

Research of the pancreatic islet: Concerns regarding the interpretation of data based on rodent studies
In the field of research of the pancreatic islet the prototypic islet is largely based on studies of normal rodent islets. Recent reports on large animals, including humans, show a difference in islet architecture. D.J. Steiner and colleagues, Illinois, suggest that „this particular species difference has raised concerns regarding the interpretation of data based on rodent studies to humans“ [7]. They investigated the striking plasticity of islet architecture and cellular composition among various species and observe changes in response to metabolic states within a single species.
Link to original article

4. INTERESTING METHODS

Effects of chemicals on reproduction
A group of researchers, funded by the European Commission, determined the hurtful effects of chemicals on reproduction reliably with animal-free methods [8]. Within the project ReProTect - a project within the 6th European Framework Program -  a ring trial, named the „Feasibility Study“, was conducted in which 10 chemicals whose toxic effects on reproduction are already well-documented from animal experiments have been tested in a blinded study. The researchers developed a completely new approach. Instead of relying on a single test, they used a test battery of 14 in vitro assays. This approach allowed a robust prediction of adverse effects on fertility and embryonic development of the test chemicals in vivo.
Link to original article

MELN assay within the project ReProTect allows to rank chemical compounds according to their affinity for the estrogen-α receptor, or identify negative chemicals
In vitro hormone receptor transactivation assays are needed as alternative tools to study interactions with sex hormone receptors. As part of the project ReProTect, a validation study with different cells which were stably transfected with an estrogen responsive gene was set up. A standard operating procedure including a prescreen assay for unknown chemicals, estrogen receptor agonist an antagonist assays was developed. Test results were obtained and show, „that the MELN assay is transferable, robust and reproducible“, explain H. Witters and colleagues [9]. The assay successfully passed the first modules of the ECVAM validation procedure.
Link to original article

Replacing the in vivo immunogenicity assay by an in vitro assay for routine testing of Hepatitis A vaccines
In the context of testing vaccine batch releases, the Agence Française de Sécurité Sanitaire des Produits de Santé (Afssaps) carried out a study to assess the feasibility of replacing the in vivo „Gold Standard“ potency assay for routine testing of Hepatitis A vaccines by a validated in-house antigen content in vitro ELISA assay. The findings of B. Poirier and colleagues [10] show a correlation between the two methods, what „encourages Afssaps to progressively switch from in vivo to in vitro assay in the framework of Hepatitis A vaccines batch release.“
Link to original article

Extraneous agent testing for purity of vaccines: Molecular tests have become a valid alternative testing method
The European Pharmacopoeia requires avian viral vaccines to be free of adventitious agents. H.-P. Ottiger points out [11], that purity testing is an essential quality requirement of immunological veterinary medicinal products. Testing for extraneous agents includes monitoring for many different viruses. „Conventional virus detection methods include serology or virus culture, however, molecular tests have become a valid alternative testing method.“ The Nucleic acid testing is fast, highly sensitive and has a higher degree of discrimination than conventional approaches. These advantages have led to the development and standardization of polymerase chain reaction (PCR) assays for the detection of a great number of avian viruses.
Link to original article

REFERENCES

[1]  M. E. Andersen: Calling on Science: Making “Alternatives” the New Gold Standard. In: Altex 27, Special Issue 2010, p. 29-37. http://www.altex.ch/resources/rPL8_Andersen2.pdf

[2] J. Kervinen et al. (2010): Potency variation of small-molecule chymase inhibitors across species. In: Biochem Pharmacol. 2010 Jun 23. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/20599788

[3]Z. Drobná et al. (2010): Interspecies differences in metabolism of arsenic by cultured primary hepatocytes. In: Toxicol Appl Pharmacol. 2010 May 15;245(1):47-56. Epub 2010 Feb 4. http://www.ncbi.nlm.nih.gov/pubmed/20138079

[4] P. Gunness et al. (2010): Comparison of the novel HK-2 human renal proximal tubular cell line with the standard LLC-PK1 cell line in studying drug-induced nephrotoxicity. In: Can J Physiol Pharmacol. 2010 Apr;88(4):448-55. http://www.ncbi.nlm.nih.gov/pubmed/20555413

[5] J. Pataricza et al. (2010): Interspecies Differences and Extracellular Calcium Dependence in the Vasorelaxing Effect of Cromakalim in Isolated Human, Porcine, and Canine Coronary Arteries. In: J Cardiovasc Pharmacol Ther. 2010 May 14. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/20431037

[6] R. Yang and B. Su (2010): Characterization and comparison of the tissue-related modules in human and mouse. In: PLoS One. 2010 Jul 22;5(7):e11730. http://www.ncbi.nlm.nih.gov/pubmed/20661448

[7] D.J. Steiner et al. (2010): Pancreatic islet plasticity: Interspecies comparison of islet architecture and composition. In: Islets. 2010 May;2(3):135-145. http://www.ncbi.nlm.nih.gov/pubmed/20657742

[8] B. Schenk et al (2010): The ReProTect Feasibility Study, a novel comprehensive in vitro approach to detect reproductive toxicants. In: Reproductive Toxicology 30 (2010) 200–218 doi:10.1016/j.reprotox.2010.05.012

[9] H. Witters et al (2010): The assessment of estrogenic or anti-estrogenic activity of chemicals by the human stably transfected estrogen sensitive MELN cell line: Results of test performance and transferability. In: Reproductive Toxicology, Volume 30, Issue 1, August 2010, Pages 60-72.  ReProTect Special Issue. doi:10.1016/j.reprotox.2010.02.008

[10] B. Poirier et al. (2010): Would an in vitro ELISA test be a suitable alternative potency method to the in vivo immunogenicity assay commonly used in the context of international Hepatitis A vaccines batch release? In: Vaccine, Volume 28, Issue 7, 17 February 2010, Pages 1796-1802. doi:10.1016/j.vaccine.2009.12.006

[11] H.-P. Ottiger (2010): Development, standardization and assessment of PCR systems for purity testing of avian viral vaccines. In: Biologicals, Volume 38, Issue 3, May 2010, Pages 381-388  Special Section (pp. 325-392): Proceedings of the IABS International Workshop on "Viral Safety and Extraneous Agents Testing for Veterinary Vaccines", doi:10.1016/j.biologicals.2010.01.015

5. LATEST NEWS

Nearly 100 state-of-the-art research groups listed at InVitroJobs.com
We are very pleased to have listed nearly 100 state-of-the-art research groups and companies on our list of working groups. These groups mainly apply or even develop non-animal research methods. Most of them are from Germany but there are also groups from the Netherlands, USA, UK, Austria, Switzerland and Spain, India and Japan. Many well known researchers are listed. Some new connections between groups could be established by now. It is one aim of this list - besides giving an overview of the current research landscape - to enlarge networks and to generate new ideas. Further groups are welcome!
List of working groups:
www.invitrojobs.com

„3R Science Award“
The „European Partnership for Alternative Approaches to Animal Testing (EPAA)“ a voluntary collaboration between the European Commission, European trade associations, and companies from 7 industry sectors, wants to accelerate the development, validation and acceptance of alternative approaches. The joint initiative announces an award up to 100.000€ to support the development and regulatory acceptance of 3Rs alternative methods.
Read more...

New computer system „Tox21“ allows testing new drugs for toxicity
The computer system Tox21 was developed by three federal agencies, NIH, EPA, and FDA. It allows testing products against human and animal cells, rather than living animals, to find chemical reactions linked to toxicity. To test potential new drugs currently between 80 and 800 animals - primarily mice and rats – are used to test each drug. The computer system will decrease this number significantly because it will in addition eliminate dangerous compounds or ineffective drugs in an early stadium. In her article from August 5, 2010, Anna Edney cites David Dix, acting deputy director of the EPA’s national center for computational toxicology: He said, using animal data to predict what will happen in humans, has been shown to be `a jump,´ because of the vast differences in species.
Link to article of A. Edney

Read more articles in the News archive-column:
www.invitrojobs.com

6. SELECTED FORTHCOMING DEADLINES

September 15, 2010:

• Deadline for proposals for the „3R Science Award“ announced by the European Partnership for Alternative Approaches to Animal Testing (EPAA) with up to 100.000€

September 30, 2010:
Deadlines

• for the 30.000€ Felix-Wankel-Forschungspreis
• for the 20.000€ Forschungspreis zur Erforschung von Ersatz- und Ergänzungsmethoden für Tierversuche
• for the Lord Dowding Fund
• for the CAAT 2010 Animal Welfare Enhancement Awards. Each award is for $6.000

For more deadlines see our Announcement-column:
www.invitrojobs.com

More details about Grants and Funding:
www.invitrojobs.com

More details about Awards:
www.invitrojobs.com


7. CLOSING REMARKS

Do you offer new jobs, internships or thesis assignments?
You can easily enter them into our portal: www.invitrojobs.com
All our services are free of charge.

We would appreciate if you install a link from your webpage to our website. Please send us a short message if you consider to establish a link.

Our platform will support ethically defensible, modern and scientifically reasonable research. InVitroJobs is a project of People for Animal Rights Germany, a non profit organization.


Yours sincerely

Your InVitroJobs-Team