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Elimination of the helminth disease, river blindness, remains challenging due to ivermectin treatment-associated adverse reactions in loiasis co-infected patients. Here, we address a deficit in preclinical research tools for filarial translational research by developing Loa loa mouse infection models. We demonstrate that adult Loa loa worms in subcutaneous tissues, circulating microfilariae (mf) and presence of filarial biomarkers in sera occur following experimental infections of lymphopenic mice deficient in interleukin (IL)-2/7 gamma-chain signaling. A microfilaraemic infection model is also achievable, utilizing immune-competent or -deficient mice infused with purified Loa mf. Ivermectin but not benzimidazole treatments induce rapid decline (>90%) in parasitaemias in microfilaraemic mice. We identify up-regulation of inflammatory markers associated with allergic type-2 immune responses and eosinophilia post-ivermectin treatment. Thus, we provide validation of murine research models to identify loiasis biomarkers, to counter-screen candidate river blindness cures and to interrogate the inflammatory etiology of loiasis ivermectin-associated adverse reactions.
This article was published in the following journal.
Name: Nature communications
SSc is a complex rheumatoid disease characterized by autoimmunity, fibrosis and vasculopathy. Mouse models provide powerful research tools for exploring the pathogenesis of the human diseases. Each mo...
Animal models are fundamental tools to study the biology of physiological processes and disease pathogenesis. To study invasive pneumococcal disease (IPD), many models using mice in particular have be...
Murine models are widely used valuable tools to study deep vein thrombosis (VT). Leading experts in VT research came together through the American Venous Forum to develop a consensus on maximizing the...
Pancreatitis is increasingly recognized as not merely a local inflammation of the pancreas but also a disease with high frequency of systemic sequelae. Current understanding of the cellular mechanisms...
Mouse models of chronic heart failure (HF) have been widely used in HF research. However, the current HF models most often use the C57BL/6 mouse strain and do not show the clinically relevant characte...
DM-CHOC-PEN is a new penclomedine analog that has demonstrated antineoplastic activities in human xenograft intracerebrally implanted tumor mouse models, acceptable preclinical toxicities ...
Using sickle cell and thalassemia mouse models, researchers will evaluate the possibility of correcting these disorders by inserting healthy genetic material into the diseased blood cells....
RATIONALE: Changing the genes in laboratory mice to create a living model of human breast cancer may help doctors learn more about breast cancer. PURPOSE: This research study is developin...
Pancreatic cancer is a very aggressive cancer. Over the past 40 years there has not been much progress made in reducing deaths from this cancer. Recently, new models of pancreatic cancers ...
The goal of this clinical research study is to use xenograft models to test the effectiveness of certain anti-cancer drugs in relapsed (has come back) or refractory (has not responded to t...
One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression.
Statistical models of the production, distribution, and consumption of goods and services, as well as of financial considerations. For the application of statistics to the testing and quantifying of economic theories MODELS, ECONOMETRIC is available.
Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...