scholarly journals Pharmacogenetic studies on the drug-related lupus syndrome. differences in antinuclear antibody development and drug-induced DNA damage in rapid and slow acetylator animal models

1981 ◽  
Vol 24 (8) ◽  
pp. 979-986 ◽  
Author(s):  
W. W. Weber ◽  
R. H. Tannen
Keyword(s):  
Dna Damage ◽  
Animal Models ◽  
Antinuclear Antibody ◽  
Drug Induced ◽  
Slow Acetylator ◽  
Lupus Syndrome

scholarly journals Hydralazine Induced Lupus Syndrome Presenting with Recurrent Pericardial Effusion and a Negative Antinuclear Antibody

2017 ◽  
Vol 2017 ◽  
pp. 1-3 ◽  
Author(s):  
Praneet Iyer ◽  
Ahmed Dirweesh ◽  
Ritika Zijoo
Keyword(s):  
Pericardial Effusion ◽  
Lupus Erythematosus ◽  
Antinuclear Antibody ◽  
Autoimmune Disorder ◽  
Unique Case ◽  
Drug Induced ◽  
Pericardial Window ◽  
Lupus Syndrome ◽  
Chronic Use ◽  
Recurrent Pericardial Effusion

Drug induced lupus erythematosus (DIL or DILE) is an autoimmune disorder caused by chronic use of certain drugs. We report a unique case of hydralazine induced lupus syndrome (HILS) with a negative antinuclear antibody in a female patient who was on hydralazine for a period of 1.5–2 years and developed recurrent pericardial effusion as a result of it. Initially her condition was managed with a pericardial window. The recurrence of a massive pericardial effusion necessitated a right hemipericardiectomy. After hydralazine was stopped, she never had any further episodes of pericardial effusion or tamponade.

Sunscreen protection against drug-induced phototoxicity in animal models

1979 ◽  
Vol 49 (2) ◽  
pp. 219-224 ◽  
Author(s):  
Frank J. Akin ◽  
Arthur P. Rose ◽  
Thomas W. Chamness ◽  
Edward Marlowe
Keyword(s):  
Animal Models ◽  
Drug Induced

scholarly journals An Overview of Animal Models Related to Schizophrenia

2018 ◽  
Vol 64 (1) ◽  
pp. 5-17 ◽  
Author(s):  
Ian R. Winship ◽  
Serdar M. Dursun ◽  
Glen B. Baker ◽  
Priscila A. Balista ◽  
Ludmyla Kandratavicius ◽  
...  
Keyword(s):  
Animal Models ◽  
Rodent Models ◽  
Preclinical Research ◽  
Drug Induced ◽  
Factors Associated ◽  
Tremendous Progress ◽  
Current Therapies ◽  
Novel Therapeutic Strategies ◽  
Development And Validation ◽  
Core Features

Schizophrenia is a heterogeneous psychiatric disorder that is poorly treated with current therapies. In this brief review, we provide an update regarding the use of animal models to study schizophrenia in an attempt to understand its aetiology and develop novel therapeutic strategies. Tremendous progress has been made developing and validating rodent models that replicate the aetiologies, brain pathologies, and behavioural abnormalities associated with schizophrenia in humans. Here, models are grouped into 3 categories—developmental, drug induced, and genetic—to reflect the heterogeneous risk factors associated with schizophrenia. Each of these models is associated with varied but overlapping pathophysiology, endophenotypes, behavioural abnormalities, and cognitive impairments. Studying schizophrenia using multiple models will permit an understanding of the core features of the disease, thereby facilitating preclinical research aimed at the development and validation of better pharmacotherapies to alter the progression of schizophrenia or alleviate its debilitating symptoms.

Potential for inhibition of checkpoint kinases 1/2 in pulmonary fibrosis and secondary pulmonary hypertension

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2021-217377
Author(s):  
Wen-Hui Wu ◽  
Sébastien Bonnet ◽  
Tsukasa Shimauchi ◽  
Victoria Toro ◽  
Yann Grobs ◽  
...  
Keyword(s):  
Dna Damage ◽  
Pulmonary Hypertension ◽  
Animal Models ◽  
Pulmonary Fibrosis ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Therapeutic Option ◽  
Checkpoint Kinases ◽  
Medical Needs ◽  
Secondary Pulmonary Hypertension

BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterised by exuberant tissue remodelling and associated with high unmet medical needs. Outcomes are even worse when IPF results in secondary pulmonary hypertension (PH). Importantly, exaggerated resistance to cell death, excessive proliferation and enhanced synthetic capacity are key endophenotypes of both fibroblasts and pulmonary artery smooth muscle cells, suggesting shared molecular pathways. Under persistent injury, sustained activation of the DNA damage response (DDR) is integral to the preservation of cells survival and their capacity to proliferate. Checkpoint kinases 1 and 2 (CHK1/2) are key components of the DDR. The objective of this study was to assess the role of CHK1/2 in the development and progression of IPF and IPF+PH.Methods and resultsIncreased expression of DNA damage markers and CHK1/2 were observed in lungs, remodelled pulmonary arteries and isolated fibroblasts from IPF patients and animal models. Blockade of CHK1/2 expression or activity-induced DNA damage overload and reverted the apoptosis-resistant and fibroproliferative phenotype of disease cells. Moreover, inhibition of CHK1/2 was sufficient to interfere with transforming growth factor beta 1-mediated fibroblast activation. Importantly, pharmacological inhibition of CHK1/2 using LY2606368 attenuated fibrosis and pulmonary vascular remodelling leading to improvement in respiratory mechanics and haemodynamic parameters in two animal models mimicking IPF and IPF+PH.ConclusionThis study identifies CHK1/2 as key regulators of lung fibrosis and provides a proof of principle for CHK1/2 inhibition as a potential novel therapeutic option for IPF and IPF+PH.

scholarly journals Kinase-dead ATM protein is highly oncogenic and can be preferentially targeted by Topo-isomerase I inhibitors

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Kenta Yamamoto ◽  
Jiguang Wang ◽  
Lisa Sprinzen ◽  
Jun Xu ◽  
Christopher J Haddock ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cancer Therapy ◽  
Animal Models ◽  
Dna Adducts ◽  
Kinase Domain ◽  
Missense Mutations ◽  
Atm Kinase ◽  
Dna Damage Responses ◽  
Atm Protein ◽  
Kinase A

Missense mutations in ATM kinase, a master regulator of DNA damage responses, are found in many cancers, but their impact on ATM function and implications for cancer therapy are largely unknown. Here we report that 72% of cancer-associated ATM mutations are missense mutations that are enriched around the kinase domain. Expression of kinase-dead ATM (AtmKD/-) is more oncogenic than loss of ATM (Atm-/-) in mouse models, leading to earlier and more frequent lymphomas with Pten deletions. Kinase-dead ATM protein (Atm-KD), but not loss of ATM (Atm-null), prevents replication-dependent removal of Topo-isomerase I-DNA adducts at the step of strand cleavage, leading to severe genomic instability and hypersensitivity to Topo-isomerase I inhibitors. Correspondingly, Topo-isomerase I inhibitors effectively and preferentially eliminate AtmKD/-, but not Atm-proficientor Atm-/- leukemia in animal models. These findings identify ATM kinase-domain missense mutations as a potent oncogenic event and a biomarker for Topo-isomerase I inhibitor based therapy.

New Associations between Drug-Induced Adverse Events in Animal Models and Humans Reveal Novel Candidate Safety Targets

2020 ◽  
Author(s):  
Kathryn A. Giblin ◽  
Danilo Basili ◽  
Avid M. Afzal ◽  
Lyn Rosenbrier-Ribeiro ◽  
Nigel Greene ◽  
...  
Keyword(s):  
Animal Models ◽  
Adverse Events ◽  
Drug Induced ◽  
New Associations
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