Publications by authors named "Ute Bach"

7 Publications

  • Page 1 of 1

Opinion on Maintaining In-House GLP Status for Toxicologic Pathology in Pharmaceutical and (Agro)Chemical Development.

Toxicol Pathol 2021 Aug 26:1926233211042256. Epub 2021 Aug 26.

Bayer S.A.S, R&D Crop Science, Sophia Antipolis, France.

Many pharmaceutical companies have recently elected to stop maintaining good laboratory practices (GLP) status of their R&D sites. Similar discussions have also been engaged in the (agro)chemical industry. This opinion paper examines the pros and cons of maintaining facility GLP status for the purposes of performing the pathology interpretation or peer reviews of GLP studies internally. The toxicologic pathologist provides gross and histomorphologic evaluation and interpretation of nonclinical exploratory and regulatory studies during drug and (agro)chemical development. This assessment significantly contributes to human risk assessment by characterizing the toxicological profile and discussing the human relevance of the findings. The toxicologic pathologist is a key contributor to compound development decisions (advancement or termination) and in the development of de-risking strategies for backup compounds, thus playing a critical role in helping to reduce the late attrition of drugs and chemicals. Maintaining GLP compliance is often perceived as a costly and cumbersome process; a common and short-term strategy to reduce the costs is to outsource regulatory toxicity studies. However, there are significant advantages in maintaining the GLP status for toxicologic pathology activities in-house including the sustainable retention of internal pathology expertise that has maintained the necessary training needed to manage GLP studies. [Box: see text].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/01926233211042256DOI Listing
August 2021

Nonproliferative and proliferative lesions of the rat and mouse female reproductive system.

J Toxicol Pathol 2014 ;27(3-4 Suppl):1S-107S

National Institute of Health Sciences, Tokyo, Japan.

The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www.toxpath.org/inhand.asp) is a joint initiative of the Societies of Toxicological Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in the female reproductive tract of laboratory rats and mice, with color photomicrographs illustrating examples of some lesions. The standardized nomenclature presented in this document is also available electronically on the internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and aging lesions as well as lesions induced by exposure to test materials. There is also a section on normal cyclical changes observed in the ovary, uterus, cervix and vagina to compare normal physiological changes with pathological lesions. A widely accepted and utilized international harmonization of nomenclature for female reproductive tract lesions in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1293/tox.27.1SDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4253081PMC
December 2014

Proceedings of the 2009 National Toxicology Program Satellite Symposium.

Toxicol Pathol 2010 Jan 15;38(1):9-36. Epub 2009 Dec 15.

1Bayer HealthCare AG, Pharma Research Center, Wuppertal, Germany.

The National Toxicology Program (NTP) Satellite Symposium is a one-day meeting that is held in conjunction with the annual Society of Toxicologic Pathology (STP) meeting. The topic of the 2009 Symposium was "Tumor Pathology and INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Nomenclature." The goal of this article is to provide summaries of each speaker's presentation, including the diagnostic or nomenclature issues that were presented, along with a few select images that were used for voting. The results of the voting process and interesting points of discussion that were raised during the presentation are also provided. A supplemental file with voting choices and voting results for each case presented at the symposium is available at http://tpx.sagepub.com/supplemental.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0192623309354111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4195590PMC
January 2010

Parasitological and morphological findings in porcine isosporosis after treatment with symmetrical triazintriones.

Parasitol Res 2003 Sep 11;91(1):27-33. Epub 2003 Jul 11.

BHC-PH-P-Toxicologic Pathology, Pharma Research Center, Bayer AG, 42096 Wuppertal, Germany.

Neonatal porcine isosporosis is known to cause serious economic losses in piglet farms by causing severe enteritis with dehydration, weight loss and reduced development in the affected animals, predominantly during the first weeks of life. In the present study, piglets experimentally infected with Isospora suis were treated with Bay Vi 9143, a symmetrical triazintrione, at different days post-infection. As shown by clinical and pathological examinations, Bay Vi 9143 is effective against the asexual and sexual stages of I. suis at all selected treatment times. However, the therapeutic use at an early stage of asexual multiplication is most effective before the onset of clinical symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00436-003-0828-3DOI Listing
September 2003

A new approach to studying ochratoxin A (OTA)-induced nephrotoxicity: expression profiling in vivo and in vitro employing cDNA microarrays.

Toxicol Sci 2003 Jun 15;73(2):315-28. Epub 2003 Apr 15.

Department of Molecular and Genetic Toxicology, Bayer AG, Aprather Weg 18a, 42096 Wuppertal, Germany.

Ochratoxin A (OTA) is a mycotoxin often found in cereals as a contaminant, and it is known to cause severe nephrotoxicity in animals and humans. There have been several investigations studying the mode of action of this toxicant, suggesting inhibition of protein synthesis, formation of DNA adducts, and provocation of DNA single-strand breaks as a result of oxidative stress, but little is known about the transcriptional alterations underlying OTA-derived nephrotoxicity so far. We carried out DNA microarray analyses to assess OTA-specific expression profiles in vivo and in vitro. Cultures of primary rat proximal tubular cells and male Wistar rats were treated with a low dose (5 microM and 1 mg/kg, respectively) or a high dose (12.5 microM and 10 mg/kg, respectively) of OTA for 24 or 72 h. Microarray experiments were carried out after dual fluorescent labeling of sample cDNA, and data analysis was performed utilizing different statistical methods. Validity of selected microarray data was confirmed by quantitative real-time PCR. We were able to demonstrate that microarray data derived from our proximal tubule cell (PTC) culture model were highly comparable to the in vivo situation. Marked treatment-specific transcriptional changes were detected for genes involved in DNA damage response and apoptosis (upregulation of GADD 153, GADD 45, annexin V), response to oxidative stress (differential expression of hypoxia-inducible factor 1 and catalase), and inflammatory reactions (upregulation of alpha 2 macroglobulin, ceruloplasmin, and cathepsin S). We conclude that our results provide a molecular basis for interpretation of OTA-induced nephrotoxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/toxsci/kfg073DOI Listing
June 2003

New helicase-primase inhibitors as drug candidates for the treatment of herpes simplex disease.

Nat Med 2002 Apr;8(4):392-8

Bayer AG, Pharma Research, Wuppertal, Germany.

The vast majority of the world population is infected with at least one member of the human herpesvirus family. Herpes simplex virus (HSV) infections are the cause of cold sores and genital herpes as well as life-threatening or sight-impairing disease mainly in immunocompromized patients, pregnant women and newborns. Since the milestone development in the late 1970s of acyclovir (Zovirax), a nucleosidic inhibitor of the herpes DNA polymerase, no new non-nucleosidic anti-herpes drugs have been introduced. Here we report new inhibitors of the HSV helicase-primase with potent in vitro anti-herpes activity, a novel mechanism of action, a low resistance rate and superior efficacy against HSV in animal models. BAY 57-1293 (N-[5-(aminosulfonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(2-pyridinyl)phenyl]acetamide), a well-tolerated member of this class of compounds, significantly reduces time to healing, prevents rebound of disease after cessation of treatment and, most importantly, reduces frequency and severity of recurrent disease. Thus, this class of drugs has significant potential for the treatment of HSV disease in humans, including those resistant to current medications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nm0402-392DOI Listing
April 2002
-->