Adenylosuccinic Acid Is a Non-Toxic Small Molecule In Vitro and In Vivo.

Adenylosuccinic acid (ASA) is a small molecule dicarboxylate that could be a strong clinical development candidate for inherited myopathies involving dysregulated purine nucleotide metabolism. Currently, there are no published pharmacokinetic/dynamic or toxicology data available, although 10-year clinical trial data on Duchenne muscular dystrophy patients suggests it is a chronically safe drug. In this study, we tested the toxicity of ASA to cultured myoblasts in vitro and its acute systemic toxicity in mice.

Observation of non-glandular gastritis associated with Doxil chemotherapy treatment in NSG™ mice.

NSG™ mice are highly immunocompromised thus demonstrate high efficiency engraftment of patient-derived xenografts (PDXs) for pre-clinical oncology research. It has previously been reported that NSG™ mice are hyper-sensitive to doxorubicin due to the impairment of DNA damage repair mechanisms. As such, doxorubicin causes a wide spectrum of toxicities including cardiotoxicity, hepatotoxicity and intestinal toxicity in NSG™ mice.

Cotargeting BCL-2 and MCL-1 in high-risk B-ALL.

Improving survival outcomes in adult B-cell acute lymphoblastic leukemia (B-ALL) remains a clinical challenge. Relapsed disease has a poor prognosis despite the use of tyrosine kinase inhibitors (TKIs) for Philadelphia chromosome positive (Ph+ ALL) cases and immunotherapeutic approaches, including blinatumomab and chimeric antigen receptor T cells. Targeting aberrant cell survival pathways with selective small molecule BH3-mimetic inhibitors of BCL-2 (venetoclax, S55746), BCL-XL (A1331852), or MCL1 (S63845) is an emerging therapeutic option.

An Atypical Parvovirus Drives Chronic Tubulointerstitial Nephropathy and Kidney Fibrosis.

The occurrence of a spontaneous nephropathy with intranuclear inclusions in laboratory mice has puzzled pathologists for over 4 decades, because its etiology remains elusive. The condition is more severe in immunodeficient animals, suggesting an infectious cause. Using metagenomics, we identify the causative agent as an atypical virus, termed "mouse kidney parvovirus" (MKPV), belonging to a divergent genus of Parvoviridae.

Intranuclear Inclusions in Renal Tubular Epithelium in Immunodeficient Mice Stain with Antibodies for Bovine Papillomavirus Type 1 L1 Protein.

The kidneys from six immunodeficient mice examined by Cerberus Sciences and the Animal Resources Centre, displayed karyomegaly with pale eosinophilic, intranuclear inclusions upon histopathological examination. Electron microscopy performed on kidney tissue from 5/6 mice demonstrated margination of the chromatin in large nuclei. Laboratory tests were used to detect nucleic acid of papillomaviruses, polyomaviruses, circoviruses and anelloviruses (4/6 mice), a specific PCR was used to detect murine polyomavirus (1/6), and a panel of serological tests was used to detect seroconversion to major murine pathogens (1/6).

Prevalence of viral, bacterial and parasitological diseases in rats and mice used in research environments in Australasia over a 5-y period.

Viral, bacterial and parasitological infections in rats and mice used in biomedical research continue to occur despite improved housing and biosurveillance. The presence of disease in laboratory animals can lead to spurious results for research undertaken in universities, research institutes and the pharmaceutical industry. Here the authors report the results of serological, microbiological, parasitological and molecular tests done on mice and rats from Australasia submitted to a rodent health monitoring laboratory (Cerberus Sciences) from 2004 to 2009.