Validation of Di-5-HT-Gd-DTPA, an Enzyme-Specific MR Contrast Agent for Myeloperoxidase, in the Rabbit Elastase Model of Cerebrovascular Aneurysm

2009 ◽  
Author(s):  
Michael J. DeLeo ◽  
Matthew J. Gounis ◽  
Ajay K. Wakhloo ◽  
Alexei A. Bogdanov
Keyword(s):  
Contrast Agent ◽  
Rabbit Model ◽  
Zealand White Rabbit ◽  
Animal Models Of Disease ◽  
Diagnostic Potential ◽  
Molecular Imaging Probes ◽  
Imaging Probes ◽  
Models Of Disease ◽  
Active Inflammation

Characterization of molecular imaging probes in multiple animal models of disease is essential to increase their diagnostic potential. For example, we recently demonstrated visualization of active inflammation in a rabbit model saccular aneurysm using clinical field strength MRI and the paramagnetic MR contrast agent di-5-HT-GdDTPA, which has been shown in vitro to be sensitive and specific for the enzyme myeloperoxidase (MPO). While the use of transgenic mice (MPO−/−) has demonstrated specificity of di-5-HT-GdDTPA for MPO in a model of myocardial infarction [1], MPO-deficient rabbits are not available. Therefore, in this study, we sought to validate di-5-HT-GdDTPA MPO specificity in the New Zealand white rabbit by comparing serial enhancement ratios of di-5-HT-GdDTPA to a structurally similar MR contrast agent, di-Tyr-GdDTPA, which is activated by peroxidases but not by MPO. Structural diagrams of the synthesis of the two agents are demonstrated in Figure 1 [2].

Potential for Treatment of Neurodegenerative Diseases with Natural Products or Synthetic Compounds that Stabilize Microtubules

2020 ◽  
Vol 26 (35) ◽  
pp. 4362-4372
Author(s):  
John H. Miller ◽  
Viswanath Das
Keyword(s):  
Natural Products ◽  
Neurodegenerative Diseases ◽  
In Vivo Models ◽  
Synthetic Compounds ◽  
Stabilizing Agents ◽  
Animal Models Of Disease ◽  
Model Studies ◽  
Models Of Disease

No effective therapeutics to treat neurodegenerative diseases exist, despite significant attempts to find drugs that can reduce or rescue the debilitating symptoms of tauopathies such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, amyotrophic lateral sclerosis, or Pick’s disease. A number of in vitro and in vivo models exist for studying neurodegenerative diseases, including cell models employing induced-pluripotent stem cells, cerebral organoids, and animal models of disease. Recent research has focused on microtubulestabilizing agents, either natural products or synthetic compounds that can prevent the axonal destruction caused by tau protein pathologies. Although promising results have come from animal model studies using brainpenetrant natural product microtubule-stabilizing agents, such as paclitaxel analogs that can access the brain, epothilones B and D, and other synthetic compounds such as davunetide or the triazolopyrimidines, early clinical trials in humans have been disappointing. This review aims to summarize the research that has been carried out in this area and discuss the potential for the future development of an effective microtubule stabilizing drug to treat neurodegenerative disease.

scholarly journals Shiga Toxin Subtypes Display Dramatic Differences in Potency

2011 ◽  
Vol 79 (3) ◽  
pp. 1329-1337 ◽  
Author(s):  
Cynthia A. Fuller ◽  
Christine A. Pellino ◽  
Michael J. Flagler ◽  
Jane E. Strasser ◽  
Alison A. Weiss
Keyword(s):  
Shiga Toxin ◽  
Vero Cells ◽  
Epidemiologic Studies ◽  
Systemic Complications ◽  
Animal Models Of Disease ◽  
Uremic Syndrome ◽  
Models Of Disease ◽  
Relative Potencies

ABSTRACTPurified Shiga toxin (Stx) alone is capable of producing systemic complications, including hemolytic-uremic syndrome (HUS), in animal models of disease. Stx includes two major antigenic forms (Stx1 and Stx2), with minor variants of Stx2 (Stx2a to -h). Stx2a is more potent than Stx1. Epidemiologic studies suggest that Stx2 subtypes also differ in potency, but these differences have not been well documented for purified toxin. The relative potencies of five purified Stx2 subtypes, Stx2a, Stx2b, Stx2c, Stx2d, and activated (elastase-cleaved) Stx2d, were studiedin vitroby examining protein synthesis inhibition using Vero monkey kidney cells and inhibition of metabolic activity (reduction of resazurin to fluorescent resorufin) using primary human renal proximal tubule epithelial cells (RPTECs). In both RPTECs and Vero cells, Stx2a, Stx2d, and elastase-cleaved Stx2d were at least 25 times more potent than Stx2b and Stx2c.In vivopotency in mice was also assessed. Stx2b and Stx2c had potencies similar to that of Stx1, while Stx2a, Stx2d, and elastase-cleaved Stx2d were 40 to 400 times more potent than Stx1.

scholarly journals Tuberculous Granulomas Are Hypoxic in Guinea Pigs, Rabbits, and Nonhuman Primates

2008 ◽  
Vol 76 (6) ◽  
pp. 2333-2340 ◽  
Author(s):  
Laura E. Via ◽  
P. Ling Lin ◽  
Sonja M. Ray ◽  
Jose Carrillo ◽  
Shannon Sedberry Allen ◽  
...  
Keyword(s):  
Animal Models ◽  
Guinea Pig ◽  
Nonhuman Primate ◽  
Culture Conditions ◽  
Low Oxygen ◽  
Animal Models Of Disease ◽  
Hypoxic Conditions ◽  
Models Of Disease ◽  
Pulmonary Granulomas

ABSTRACT Understanding the physical characteristics of the local microenvironment in which Mycobacterium tuberculosis resides is an important goal that may allow the targeting of metabolic processes to shorten drug regimens. Pimonidazole hydrochloride (Hypoxyprobe) is an imaging agent that is bioreductively activated only under hypoxic conditions in mammalian tissue. We employed this probe to evaluate the oxygen tension in tuberculous granulomas in four animal models of disease: mouse, guinea pig, rabbit, and nonhuman primate. Following infusion of pimonidazole into animals with established infections, lung tissues from the guinea pig, rabbit, and nonhuman primate showed discrete areas of pimonidazole adduct formation surrounding necrotic and caseous regions of pulmonary granulomas by immunohistochemical staining. This labeling could be substantially reduced by housing the animal under an atmosphere of 95% O2. Direct measurement of tissue oxygen partial pressure by surgical insertion of a fiber optic oxygen probe into granulomas in the lungs of living infected rabbits demonstrated that even small (3-mm) pulmonary lesions were severely hypoxic (1.6 ± 0.7 mm Hg). Finally, metronidazole, which has potent bactericidal activity in vitro only under low-oxygen culture conditions, was highly effective at reducing total-lung bacterial burdens in infected rabbits. Thus, three independent lines of evidence support the hypothesis that hypoxic microenvironments are an important feature of some lesions in these animal models of tuberculosis.

scholarly journals Immunomodulatory Properties of Polyphenol-Rich Sugarcane Extract on Human Monocytes

Biologics ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 211-221
Author(s):  
Jack Feehan ◽  
Monica D. Prakash ◽  
Lily Stojanovska ◽  
Matthew Roland Flavel ◽  
Barry Kitchen ◽  
...  
Keyword(s):  
Human Monocyte ◽  
Immunomodulatory Effect ◽  
Plant Polyphenols ◽  
Future Studies ◽  
Animal Models Of Disease ◽  
Beneficial Effects ◽  
Immunomodulatory Properties ◽  
High Concentrations ◽  
Models Of Disease

As inflammatory lifestyle factors become more prevalent and as the population ages, the management of inflammation will become increasingly relevant. Plant polyphenols are powerful antioxidants that are known to have beneficial effects in a number of diseases with an inflammatory or oxidative component, such as malignancy, cardiovascular disease and arthritis. Polyphenol-rich sugarcane extract (PRSE) is a novel preparation with high concentrations of polyphenolic antioxidants, with some evidence to show benefits in health, but there is limited research investigating its effects on immunomodulation. This study determined the effects of PRSE on human monocyte cells in vitro. We show that PRSE has an immunomodulatory effect in U937 human monocyte cells, altering the expression of cellular surface markers, with an increased expression of CD16 and CD11b, as well as small changes in CD40, CD80, CD80, CD206 and MHCI. It also modulates the profile of secreted cytokines, increasing IL-1β, TNFα, IL-6, IL-8, IL-4 and IL-10. These changes are consistent with the advanced differentiation of the monocyte, as well as the switch from the M1 to M2 phenotype in macrophages. We also demonstrate that this effect is likely to be independent of the NF-κB signalling pathway, suggesting that other mechanisms drive this effect. PRSE exerts an immunomodulatory effect on U937 monocytes in vitro, potentially facilitating the conversion from inflammation to healing. Future studies should identify specific mechanisms underlying the changes and evaluate their effectiveness in animal models of disease.

scholarly journals Multimodal Imaging Probe for Melanoma Evaluating of PTK7 Expression by Sgc8-c Aptamer Recognition

2021 ◽  
Author(s):  
Estefanía Sicco ◽  
Amy Mónaco ◽  
Marcelo Fernandez ◽  
María Moreno ◽  
Victoria Calzada ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Dna Aptamer ◽  
Specific Expression ◽  
Imaging Probe ◽  
Molecular Imaging Probes ◽  
Imaging Probes ◽  
Diagnosis Of Cancer ◽  
Animal Tumor

Abstract Melanoma is one of the most aggressive and deadly skin cancers, and although histopathological criteria are used for its prognosis, biomarkers are necessary to identify the different evolution stages. The applications of molecular imaging include the in vivo diagnosis of cancer with probes that recognize the tumor-biomarkers specific expression allowing external images acquisitions and evaluations of the biological process in quali-quantitative ways. Aptamers are oligonucleotides that recognize targets with high affinity and specificity presenting advantages that make them interesting molecular imaging probes. Sgc8-c (DNA-aptamer) selectively recognizes PTK7-receptor overexpressed in various types of tumors. Herein, Sgc8-c was evaluated, in two melanoma models, non-metastatic and metastatic, as molecular imaging probe for in vivo diagnostic. Firstly, two probes, radio- and fluorescent-probe, were in vitro evaluated verifying the high specific PTK7 recognition and its internalization in tumor cells by the endosomal route. Secondly, in vivo proof of concept was performed in animal tumor models. Likewise, they have rapid clearance from blood exhibiting excellent target (tumor)/non-target organ ratios. Furthermore, optimal biodistribution was observed 24 hours after probes-injections accumulating almost exclusively in the tumor tissue. Sgc8-c is a potential tool for their specific use in the early detection of melanoma.

scholarly journals A Novel Small Molecule Inhibits Intrahepatocellular Accumulation of Z-Variant Alpha 1-Antitrypsin In Vitro and In Vivo

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1586 ◽  
Author(s):  
Xiaojuan Zhang ◽  
Kien Pham ◽  
Danmeng Li ◽  
Ryan J. Schutte ◽  
David Hernandez Gonzalo ◽  
...  
Keyword(s):  
Liver Disease ◽  
Cell Model ◽  
Curative Therapy ◽  
Animal Models Of Disease ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin ◽  
Models Of Disease

Alpha 1-antitrypsin deficiency (AATD) is the most common genetic cause of liver disease in children and is associated with early-onset chronic liver disease in adults. AATD associated liver injury is caused by hepatotoxic retention of polymerized mutant alpha 1-antitrypsin molecules within the endoplasmic reticulum. Currently, there is no curative therapy for AATD. In this study, we selected small molecules with the potential to bind mutant alpha 1-antitrypsin (Z-variant) to inhibit its accumulation in hepatocytes. We used molecular docking to select candidate compounds that were validated in cell and animal models of disease. A crystal structure of polymerized alpha 1-antitrypsin molecule was used as the basis for docking 139,735 compounds. Effects of the top scoring compounds were investigated in a cell model that stably expresses Z-variant alpha 1-antitrypsin and in PiZ mice expressing Z-variant human alpha 1-antitrypsin (Z-hAAT), encoded by SERPINA1*E342K. 4′,′5-(Methylenedioxy)-2-nitrocinnamic acid was predicted to bind cleaved alpha 1-antitrypsin at the polymerization interface, and observed to co-localize with Z-hAAT, increase Z-hAAT degradation, inhibit intracellular accumulation of Z-hAAT, and alleviate liver fibrosis.

Study on Protein Nanomarker Combined with Vascular Endothelial Growth Factor to Improve Vascularization of Rabbit Urethral Defect Tissue Engineering

2022 ◽  
Vol 12 (4) ◽  
pp. 673-680
Author(s):  
Min Yang ◽  
Guixi Liu ◽  
Qiao Ying
Keyword(s):  
Tissue Engineering ◽  
Urinary Tract ◽  
New Technology ◽  
Rabbit Model ◽  
Zealand White Rabbit ◽  
Polyglycolic Acid ◽  
Control Group ◽  
Observation Group ◽  
Urethral Defect

To construct the tissue engineering urethral material that is closest to the normal urethral structure in the true sense in vitro. Abdominal ADSC from a 2-month-old New Zealand white rabbit was extracted and directly compounded with non-woven polyglycolic acid (PGA) (control group) to induce the differentiation of myoblasts and epithelial-like cells in vitro and shaped into urethral structure lumen Observation group); After Gd chelating protein nano-labeling and VEGF-loaded sustained release, the rabbit model of a long urethral defect was replanted and cultured for 4 weeks, 8 weeks and 12 weeks, respectively. There was no difference in urinary tract patency rate, urinary tract infection, and renal dysfunction rate between the two groups (P > 0.05). The urine flow rate in the observation group was significantly higher than that in the control group, and the residual volume decreased (P < 0.05). The blood vessel density and CD31 percentage in the observation group increased (P < 0.05). Compared with the conventional ADSC directly in contact with the composite material to construct the urethra, in vitro induction of ADSC to myoblasts and epithelial-like cells respectively, and then use the cell membrane technology to build a tissue engineering urethral material that is closest to the normal urethral structure in the true sense, and loaded with VEGF Loop release technology can significantly improve urodynamic functions, optimize tissue engineering urethral structure and vascularization, and is expected to become a new technology for constructing new tissue engineering urethral materials.

scholarly journals Detection of L1, infectious virions and anti-L1 antibody in domestic rabbits infected with cottontail rabbit papillomavirus

2007 ◽  
Vol 88 (12) ◽  
pp. 3286-3293 ◽  
Author(s):  
Jiafen Hu ◽  
Lynn R. Budgeon ◽  
Nancy M. Cladel ◽  
Timothy D. Culp ◽  
Karla K. Balogh ◽  
...  
Keyword(s):  
Rabbit Model ◽  
Zealand White Rabbit ◽  
Sylvilagus Floridanus ◽  
Cottontail Rabbit ◽  
Domestic Rabbit ◽  
Domestic Rabbits ◽  
L1 Protein ◽  
Natural Virus

Shope papillomavirus or cottontail rabbit papillomavirus (CRPV) is one of the first small DNA tumour viruses to be characterized. Although the natural host for CRPV is the cottontail rabbit (Sylvilagus floridanus), CRPV can infect domestic laboratory rabbits (Oryctolagus cuniculus) and induce tumour outgrowth and cancer development. In previous studies, investigators attempted to passage CRPV in domestic rabbits, but achieved very limited success, leading to the suggestion that CRPV infection in domestic rabbits was abortive. The persistence of specific anti-L1 antibody in sera from rabbits infected with either virus or viral DNA led us to revisit the questions as to whether L1 and infectious CRPV can be produced in domestic rabbit tissues. We detected various levels of L1 protein in most papillomas from CRPV-infected rabbits using recently developed monoclonal antibodies. Sensitive in vitro infectivity assays additionally confirmed that extracts from these papillomas were infectious. These studies demonstrated that the CRPV/New Zealand White rabbit model could be used as an in vivo model to study natural virus infection and viral life cycle of CRPV and not be limited to studies on abortive infections.

scholarly journals Nanobodies as Versatile Tool for Multiscale Imaging Modalities

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1695
Author(s):  
Marco Erreni ◽  
Tilo Schorn ◽  
Francesca D’Autilia ◽  
Andrea Doni
Keyword(s):  
Molecular Imaging ◽  
Super Resolution ◽  
Imaging Modalities ◽  
Molecular Imaging Probes ◽  
Imaging Probes ◽  
Versatile Tool ◽  
And Function ◽  
Preclinical And Clinical Studies

Molecular imaging is constantly growing in different areas of preclinical biomedical research. Several imaging methods have been developed and are continuously updated for both in vivo and in vitro applications, in order to increase the information about the structure, localization and function of molecules involved in physiology and disease. Along with these progresses, there is a continuous need for improving labeling strategies. In the last decades, the single domain antigen-binding fragments nanobodies (Nbs) emerged as important molecular imaging probes. Indeed, their small size (~15 kDa), high stability, affinity and modularity represent desirable features for imaging applications, providing higher tissue penetration, rapid targeting, increased spatial resolution and fast clearance. Accordingly, several Nb-based probes have been generated and applied to a variety of imaging modalities, ranging from in vivo and in vitro preclinical imaging to super-resolution microscopy. In this review, we will provide an overview of the state-of-the-art regarding the use of Nbs in several imaging modalities, underlining their extreme versatility and their enormous potential in targeting molecules and cells of interest in both preclinical and clinical studies.

CLIC1 antibody conjugated nanoscale contrast agent as a sensitive and targeted molecular imaging probe for gallbladder cancer diagnosis

RSC Advances ◽  
2016 ◽  
Vol 6 (29) ◽  
pp. 24104-24110 ◽  
Author(s):  
Wei Lu ◽  
Ning Wang ◽  
YanYan Chu ◽  
Linzhu Zhou ◽  
Maolan Li ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Contrast Agent ◽  
Contrast Agents ◽  
Gallbladder Cancer ◽  
Cancer Diagnosis ◽  
Imaging Probe ◽  
Molecular Imaging Probes ◽  
Imaging Probes ◽  
Molecular Imaging Probe ◽  
Targeted Molecular Imaging

CLIC1 antibody-conjugated nano-scale contrast agents exhibit a fast and sensitive detection of gallbladder tumors and may be used in the future as powerful targeted molecular imaging probes for gallbladder cancer diagnosis.

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