scholarly journals uPA+/+-SCID Mouse with Humanized Liver as a Model for In Vivo Metabolism of Exogenous Steroids: Methandienone as a Case Study

2009 ◽  
Vol 55 (10) ◽  
pp. 1783-1793 ◽  
Author(s):  
Leen Lootens ◽  
Philip Meuleman ◽  
Oscar J Pozo ◽  
Peter Van Eenoo ◽  
Geert Leroux-Roels ◽  
...  
Keyword(s):  
Animal Model ◽  
Scid Mouse ◽  
Small Animal ◽  
Steroid Metabolism ◽  
Control Analysis ◽  
Chimeric Mouse ◽  
Small Animal Model ◽  
Suitable Alternative

Abstract Background: Adequate detection of designer steroids in the urine of athletes is still a challenge in doping control analysis and requires knowledge of steroid metabolism. In this study we investigated whether uPA+/+-SCID mice carrying functional primary human hepatocytes in their liver would provide a suitable alternative small animal model for the investigation of human steroid metabolism in vivo. Methods: A quantitative method based on liquid chromatography–tandem mass spectrometry (LC-MS/MS) was developed and validated for the urinary detection of 7 known methandienone metabolites. Application of this method to urine samples from humanized mice after methandienone administration allowed for comparison with data from in vivo human samples and with reported methandienone data from in vitro hepatocyte cultures. Results: The LC-MS/MS method validation in mouse and human urine indicated good linearity, precision, and recovery. Using this method we quantified 6 of 7 known human methandienone metabolites in the urine of chimeric mice, whereas in control nonchimeric mice we detected only 2 metabolites. These results correlated very well with methandienone metabolism in humans. In addition, we detected 4 isomers of methandienone metabolites in both human and chimeric mouse urine. One of these isomers has never been reported before. Conclusions: The results of this proof-of-concept study indicate that the human liver–uPA+/+-SCID mouse appears to be a suitable small animal model for the investigation of human-type metabolism of anabolic steroids and possibly also for other types of drugs and medications. .

scholarly journals Establishment of Tree Shrew Animal Model for Kaposi’s Sarcoma-Associated Herpesvirus (HHV-8) Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Daoqun Li ◽  
Zulqarnain Baloch ◽  
Yang Zhao ◽  
Lei Bai ◽  
Xing Wang ◽  
...  
Keyword(s):  
Animal Model ◽  
Kaposi's Sarcoma ◽  
Tree Shrew ◽  
Small Animal ◽  
Kaposi’S Sarcoma ◽  
Primary Cells ◽  
Small Animal Model ◽  
Tree Shrews

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the most common cause of Kaposi’s sarcoma (KS) and other malignant growths in humans. However, the lack of a KSHV-infected small animal model has hampered understanding of the mechanisms of KSHV infection, virus replication, pathogenesis, and persistence. This study was designed to explore the susceptibility of tree shrews as a possible KSHV-infected small animal model. A recombinant GFP (latent)/RFP (lytic)-positive rKSHV.219 strain was used to infect primary cells cultured from different tissues of tree shrews as an in vitro model and adult tree shrews as an in vivo model. KSHV latent nuclear antigen (LANA) and DNA were successfully detected in primary cells of tree shrews. Among them, tree shrew kidney epithelial cells (TSKEC) were the most susceptible cells to KSHV infection compared to other cells. KSHV genomic DNA, mRNA, and KSHV-specific proteins were readily detected in the TSKEC cultured up to 32 dpi. Moreover, KSHV DNA and mRNA transcription were also readily detected in the peripheral blood mononuclear cells (PBMCs) and various tissues of tree shrews infected with KSHV. Haematoxylin and eosin (HE) staining showed lymphocyte infiltration, lymphoid tissue focal aggregation, alveolar wall thickening, hepatocyte edema, hepatic necrosis in the spleen, lung, and liver of KSHV-infected animals. Additionally, immune-histochemical (IHC) staining showed that LANA or ORF62-positive cells were present in the spleen, lung, liver, and kidney of KSHV-infected tree shrews. Here, we have successfully established in vitro and in vivo KSHV latent infection in tree shrews. This small animal model is not only useful for studying the pathogenesis of KSHV in vivo but can also be a useful model to study transmission routes of viral infection and a useful platform to characterize the novel therapeutics against KSHV.

scholarly journals Development and Characterization of a Guinea Pig-Adapted Sudan Virus

2015 ◽  
Vol 90 (1) ◽  
pp. 392-399 ◽  
Author(s):  
Gary Wong ◽  
Shihua He ◽  
Haiyan Wei ◽  
Andrea Kroeker ◽  
Jonathan Audet ◽  
...  
Keyword(s):  
Animal Model ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Lethal Dose ◽  
Fatal Outcome ◽  
Small Animal ◽  
Disease Outbreak ◽  
Small Animal Model ◽  
Content Type

ABSTRACT Infections with Sudan virus (SUDV), a member of the genus Ebolavirus , result in a severe hemorrhagic fever with a fatal outcome in over 50% of human cases. The paucity of prophylactics and therapeutics against SUDV is attributed to the lack of a small-animal model to screen promising compounds. By repeatedly passaging SUDV within the livers and spleens of guinea pigs in vivo , a guinea pig-adapted SUDV variant (SUDV-GA) uniformly lethal to these animals, with a 50% lethal dose (LD 50 ) of 5.3 × 10 −2 50% tissue culture infective doses (TCID 50 ), was developed. Animals infected with SUDV-GA developed high viremia and died between 9 and 14 days postinfection. Several hallmarks of SUDV infection, including lymphadenopathy, increased liver enzyme activities, and coagulation abnormalities, were observed. Virological analyses and gross pathology, histopathology, and immunohistochemistry findings indicate that SUDV-GA replicates in the livers and spleens of infected animals similarly to SUDV infections in nonhuman primates. These developments will accelerate the development of specific medical countermeasures in preparation for a future disease outbreak due to SUDV. IMPORTANCE A disease outbreak due to Ebola virus (EBOV), suspected to have emerged during December 2013 in Guinea, with over 11,000 dead and 28,000 infected, is finally winding down. Experimental EBOV vaccines and treatments were administered to patients under compassionate circumstances with promising results, and availability of an approved countermeasure appears to be close. However, the same range of experimental candidates against a potential disease outbreak caused by other members of the genus Ebolavirus , such as Sudan virus (SUDV), is not readily available. One bottleneck contributing to this situation is the lack of a small-animal model to screen promising drugs in an efficient and economical manner. To address this, we have generated a SUDV variant (SUDV-GA) that is uniformly lethal to guinea pigs. Animals infected with SUDV-GA develop disease similar to that of SUDV-infected humans and monkeys. We believe that this model will significantly accelerate the development of life-saving measures against SUDV infections.

Evaluation of cryopreserved human hepatocytes for functional studies in vitro and in a small animal model

2005 ◽  
Vol 43 (05) ◽  
Author(s):  
KL Streetz ◽  
M Elazar ◽  
S Levenberg ◽  
MS Chua ◽  
D Wang ◽  
...  
Keyword(s):  
Animal Model ◽  
Small Animal ◽  
Human Hepatocytes ◽  
Small Animal Model ◽  
Functional Studies

scholarly journals In vivo performance of an acellular disc-like angle ply structure (DAPS) for total disc replacement in a small animal model

2016 ◽  
Vol 35 (1) ◽  
pp. 23-31 ◽  
Author(s):  
John T. Martin ◽  
Dong Hwa Kim ◽  
Andrew H. Milby ◽  
Christian G. Pfeifer ◽  
Lachlan J. Smith ◽  
...  
Keyword(s):  
Animal Model ◽  
Total Disc Replacement ◽  
Small Animal ◽  
Disc Replacement ◽  
Small Animal Model

scholarly journals Influence of Indomethacin on Steroid Metabolism: Endocrine Disruption and Confounding Effects in Urinary Steroid Profiling of Anti-Doping Analyses

Metabolites ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 463
Author(s):  
Anna Stoll ◽  
Michele Iannone ◽  
Giuseppina De Gregorio ◽  
Francesco Molaioni ◽  
Xavier de la Torre ◽  
...  
Keyword(s):  
Steroid Metabolism ◽  
Control Analysis ◽  
As Doping ◽  
Steroid Profiling ◽  
Steroid Profile ◽  
World Anti Doping Agency ◽  
Androgenic Steroids ◽  
Endogenous Steroid

Anabolic androgenic steroids (AAS) are prohibited as doping substances in sports by the World Anti-Doping Agency. Concentrations and concentration ratios of endogenous AAS (steroid profile markers) in urine samples collected from athletes are used to detect their administration. Certain (non-prohibited) drugs have been shown to influence the steroid profile and thereby sophisticate anti-doping analysis. It was shown in vitro that the non-steroidal anti-inflammatory drug (NSAID) indomethacin inhibits selected steroid-biotransformations catalyzed by the aldo-keto reductase (AKR) 1C3, which plays a key role in the endogenous steroid metabolism. Kinetic parameters for the indomethacin-mediated inhibition of the AKR1C3 catalyzed reduction in etiocholanolone were determined in vitro using two comparing methods. As NSAIDs are very frequently used (not only) by athletes, the inhibitory impact of indomethacin intake on the steroid metabolism was evaluated, and steroid profile alterations were detected in vivo (one male and one female volunteer). Significant differences between samples collected before, during or after the intake of indomethacin for selected steroid profile markers were observed. The presented results are of relevance for the interpretation of results from doping control analysis. Additionally, the administration of NSAIDs should be carefully reconsidered due to their potential as endocrine disruptors.

The Establishment and Application of Three Kinds of the SCID Mouse-Based Improved Animal Models in the Research of AIDS, Chronic Hepatitis B and C

2013 ◽  
Vol 749 ◽  
pp. 433-438
Author(s):  
Dong Liang Xie ◽  
Jun Yao He ◽  
Yan Ling Wu ◽  
Wen Zhang ◽  
Yoshimasa Tanaka
Keyword(s):  
Animal Model ◽  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Mouse Models ◽  
Scid Mouse ◽  
Severe Combined Immunodeficiency ◽  
Small Animal ◽  
Small Animal Model ◽  
Difficult Challenge

The SCID mouse (severe combined immunodeficiency mouse) has been used as a small animal model in the analysis of human pathophysiology and preclinical experiment for many years. As the most difficult challenge faced in the research of AIDS, chronic hepatitis B and chronic hepatitis C is the lack of appropriate small animal model, researchers have always attempted to develop a series of mouse models based on the improvements of the SCID mouse. This review focuses on the developments and applications of such SCID mouse models in three types of the above chronic infectious diseases.

scholarly journals In Vivo PET Imaging of the Activated Immune Environment in a Small Animal Model of Inflammatory Arthritis

2017 ◽  
Vol 16 ◽  
pp. 153601211771263 ◽  
Author(s):  
Benjamin L. Franc ◽  
Sam Goth ◽  
John MacKenzie ◽  
Xiaojuan Li ◽  
Joseph Blecha ◽  
...  
Keyword(s):  
Animal Model ◽  
Pet Imaging ◽  
Inflammatory Arthritis ◽  
Small Animal ◽  
Small Animal Model
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