255-LB: Impaired Gsa/cAMP Signaling Exclusive to Pancreatic ß-Cells Exhibits a Unique Urinary Metabolome via Nontargeted Metabolomics in a Murine Model of Diabetes In Vivo

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 255-LB
Author(s):  
AMRO ILAIWY ◽  
MEGAN CAPOZZI ◽  
JENNIFER L. BROWN ◽  
DAVID D’ALESSIO ◽  
JONATHAN CAMPBELL
Keyword(s):  
Murine Model ◽  
Camp Signaling

In vivo imaging reveals prostate pathology in the PTEN knockout murine model of prostate cancer

2016 ◽  
Author(s):  
Alysha Bhatti ◽  
Almeida Gilberto Serrano de ◽  
Serena Tommasini Ghelfi ◽  
Alwyn Dart ◽  
Anabel Varela-Carver ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Murine Model ◽  
In Vivo Imaging

scholarly journals In vivo evaluation of a recombinant N-acylhomoserine lactonase formulated in a hydrogel using a murine model infected with MDR Pseudomonas aeruginosa clinical isolate, CCASUP2

AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masarra M. Sakr ◽  
Walid F. Elkhatib ◽  
Khaled M. Aboshanab ◽  
Eman M. Mantawy ◽  
Mahmoud A. Yassien ◽  
...  
Keyword(s):  
Survival Rate ◽  
Murine Model ◽  
Histopathological Examination ◽  
Healing Process ◽  
Bacterial Count ◽  
Treated Group ◽  
Control Group ◽  
In Vivo Evaluation ◽  
Systemic Spread

AbstractFailure in the treatment of P. aeruginosa, due to its broad spectrum of resistance, has been associated with increased patient mortality. One alternative approach for infection control is quorum quenching which was found to decrease virulence of such pathogen. In this study, the efficiency of a recombinant Ahl-1 lactonase formulated as a hydrogel was investigated to control the infection of multidrug resistant (MDR) P. aeruginosa infected burn using a murine model. The recombinant N-acylhomoserine lactonase (Ahl-1) was formulated as a hydrogel. To test its ability to control the infection of MDR P. aeruginosa, a thermal injury model was used. Survival rate, and systemic spread of the infection were evaluated. Histopathological examination of the animal dorsal skin was also done for monitoring the healing and cellular changes at the site of infection. Survival rate in the treated group was 100% relative to 40% in the control group. A decrease of up to 3 logs of bacterial count in the blood samples of the treated animals relative to the control group and a decrease of up to 4 logs and 2.3 logs of bacteria in lung and liver samples, respectively were observed. Histopathological examination revealed more enhanced healing process in the treated group. Accordingly, by promoting healing of infected MDR P. aeruginosa burn and by reducing systemic spread of the infection as well as decreasing mortality rate, Ahl-1 hydrogel application is a promising strategy that can be used to combat and control P. aeruginosa burn infections.

scholarly journals Preclinical Studies in Anti-Trypanosomatidae Drug Development

2021 ◽  
Vol 14 (7) ◽  
pp. 644
Author(s):  
Cintya Perdomo ◽  
Elena Aguilera ◽  
Ileana Corvo ◽  
Paula Faral-Tello ◽  
Elva Serna ◽  
...  
Keyword(s):  
Rural Communities ◽  
Chagas Disease ◽  
Murine Model ◽  
Mammalian Cells ◽  
Drug Candidate ◽  
Murine Macrophages ◽  
Causative Agents ◽  
Trypanosomatid Parasites

The trypanosomatid parasites Trypanosoma brucei, Trypanosoma cruzi and Leishmania are the causative agents of human African trypanosomiasis, Chagas Disease and Leishmaniasis, respectively. These infections primarily affect poor, rural communities in the developing world, and are responsible for trapping sufferers and their families in a disease/poverty cycle. The development of new chemotherapies is a priority given that existing drug treatments are problematic. In our search for novel anti-trypanosomatid agents, we assess the growth-inhibitory properties of >450 compounds from in-house and/or “Pathogen Box” (PBox) libraries against L. infantum, L. amazonensis, L.braziliensis, T. cruzi and T. brucei and evaluate the toxicities of the most promising agents towards murine macrophages. Screens using the in-house series identified 17 structures with activity against and selective toward Leishmania: Compounds displayed 50% inhibitory concentrations between 0.09 and 25 μM and had selectivity index values >10. For the PBox library, ~20% of chemicals exhibited anti-parasitic properties including five structures whose activity against L. infantum had not been reported before. These five compounds displayed no toxicity towards murine macrophages over the range tested with three being active in an in vivo murine model of the cutaneous disease, with 100% survival of infected animals. Additionally, the oral combination of three of them in the in vivo Chagas disease murine model demonstrated full control of the parasitemia. Interestingly, phenotyping revealed that the reference strain responds differently to the five PBox-derived chemicals relative to parasites isolated from a dog. Together, our data identified one drug candidate that displays activity against Leishmania and other Trypanosomatidae in vitro and in vivo, while exhibiting low toxicity to cultured mammalian cells and low in vivo acute toxicity.

scholarly journals Sulfated poly-amido-saccharides (sulPASs) are anticoagulants in vitro and in vivo

2021 ◽  
Vol 12 (38) ◽  
pp. 12719-12725
Author(s):  
Maria Varghese ◽  
Rae S. Rokosh ◽  
Carolyn A. Haller ◽  
Stacy L. Chin ◽  
Jiaxuan Chen ◽  
...  
Keyword(s):  
Murine Model ◽  
Protamine Sulfate ◽  
Clotting Time ◽  
Risk Of Bleeding ◽  
Increased Risk

Heparin mimicking sulfated poly-amido-saccharides (sulPASs) are anticoagulants resistant to heparanases and reversed by protamine sulfate. In an in vivo murine model, sulPASs extend clotting time without the increased risk of bleeding.

In vivo murine model of acquired resistance in myeloma reveals differential mechanisms for lenalidomide and pomalidomide in combination with dexamethasone

Leukemia ◽  
2014 ◽  
Vol 29 (3) ◽  
pp. 705-714 ◽  
Author(s):  
E M Ocio ◽  
D Fernández-Lázaro ◽  
L San-Segundo ◽  
L López-Corral ◽  
L A Corchete ◽  
...  
Keyword(s):  
Murine Model ◽  
Acquired Resistance

scholarly journals Protection Elicited by Two Glutamine Auxotrophs of Mycobacterium tuberculosis and In Vivo Growth Phenotypes of the Four Unique Glutamine Synthetase Mutants in a Murine Model

2006 ◽  
Vol 74 (11) ◽  
pp. 6491-6495 ◽  
Author(s):  
Sunhee Lee ◽  
Bo-Young Jeon ◽  
Svetoslav Bardarov ◽  
Mei Chen ◽  
Sheldon L. Morris ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Glutamine Synthetase ◽  
Mycobacterium Bovis ◽  
Murine Model ◽  
Triple Mutant ◽  
Auxotrophic Mutants ◽  
Bcg Vaccination ◽  
In Vivo Growth ◽  
Subcutaneous Immunization

ABSTRACT We generated four individual glutamine synthetase (GS) mutants (ΔglnA1, ΔglnA2, ΔglnA3, and ΔglnA4) and one triple mutant (ΔglnA1EA2) of Mycobacterium tuberculosis to investigate the roles of GS enzymes. Subcutaneous immunization with the ΔglnA1EA2 and ΔglnA1 glutamine auxotrophic mutants conferred protection on C57BL/6 mice against an aerosol challenge with virulent M. tuberculosis, which was comparable to that provided by Mycobacterium bovis BCG vaccination.

scholarly journals Quantitation of Candida albicans Ergosterol Content Improves the Correlation between In Vitro Antifungal Susceptibility Test Results and In Vivo Outcome after Fluconazole Treatment in a Murine Model of Invasive Candidiasis

2000 ◽  
Vol 44 (8) ◽  
pp. 2081-2085 ◽  
Author(s):  
Beth A. Arthington-Skaggs ◽  
David W. Warnock ◽  
Christine J. Morrison
Keyword(s):  
Murine Model ◽  
Invasive Candidiasis ◽  
Clinical Laboratory ◽  
Antifungal Susceptibility ◽  
Resistant Isolate ◽  
National Committee ◽  
Ergosterol Content ◽  
In Vitro Antifungal Susceptibility

ABSTRACT MIC end point determination for the most commonly prescribed azole antifungal drug, fluconazole, can be complicated by “trailing” growth of the organism during susceptibility testing by the National Committee for Clinical Laboratory Standards approved M27-A broth macrodilution method and its modified broth microdilution format. To address this problem, we previously developed the sterol quantitation method (SQM) for in vitro determination of fluconazole susceptibility, which measures cellular ergosterol content rather than growth inhibition after exposure to fluconazole. To determine if SQM MICs of fluconazole correlated better with in vivo outcome than M27-A MICs, we used a murine model of invasive candidiasis and analyzed the capacity of fluconazole to treat infections caused by C. albicansisolates which were trailers (M27-A MICs at 24 and 48 h, ≤1.0 and ≥64 μg/ml, respectively; SQM MIC, ≤1.0 μg/ml), as well as those which were fluconazole sensitive (M27-A and SQM MIC, ≤1.0 μg/ml) and fluconazole resistant (M27-A MIC, ≥64 μg/ml; SQM MIC, 54 μg/ml). Compared with the untreated controls, fluconazole therapy increased the survival of mice infected with a sensitive isolate and both trailing isolates but did not increase the survival of mice infected with a resistant isolate. These results indicate that the SQM is more predictive of in vivo outcome than the M27-A method for isolates that give unclear MIC end points due to trailing growth in fluconazole.

Abstract 201: Generation of Photoactivatable apoA I to Study HDL Transport in vivo Reveals Impaired HDL Recirculation in a Murine Model of Psoriasis

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Li-Hao Huang ◽  
Bernd H Zinselmeyer ◽  
Chih-Hao Chang ◽  
Brian T Saunders ◽  
Brian S Kim ◽  
...  
Keyword(s):  
T Cell ◽  
Murine Model ◽  
Structural Changes ◽  
Cardiovascular Outcomes ◽  
Dependent Manner ◽  
Cardiovascular Comorbidity ◽  
Collagen Density

HDL is cardioprotective, but plasma HDL levels do not necessarily predict cardiovascular outcomes. The major HDL-associated protein apoA-I picks up its cholesterol from cells within extravascular compartments to return it to plasma and then bile. Yet, tools are lacking to quantify the important step of HDL transit through extravascular spaces. Here, we developed recombinant photoactivatable apoA-I to quantify endogenous HDL recirculation. Using the tool, we studied HDL passage through skin in healthy mice versus those with experimental psoriasis, wherein collagen density increased in the skin in a CD4 + T cell-dependent manner. In control mice, photoactivated HDL mobilized to plasma within 2 h but was retained in collagen-enriched skin of mice with psoriasis. These data suggest that cardiovascular comorbidity in psoriasis might be linked to T cell-mediated structural changes in skin that impedes systemic recirculation of HDL. This new tool is likely to find wide application in HDL research.

In vivo molecular analysis of cytokines in a murine model of ocular onchocerciasis I. Up-regulation of IL-4 and IL-5 mRNAs and not IL-2 and IFNγ mRNAs in the cornea due to experimental interstitial keratitis

1996 ◽  
Vol 54 (1) ◽  
pp. 59-64 ◽  
Author(s):  
Bulbul Chakravarti ◽  
Sandhya Lagoo-Deenadayalan ◽  
John S. Parker ◽  
David R. Whitfield ◽  
Anand Lagoo ◽  
...  
Keyword(s):  
Molecular Analysis ◽  
Murine Model ◽  
Interstitial Keratitis
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