Search results for "disease model"
showing 10 items of 1116 documents
Anti-Hypotensive Treatment and Endothelin Blockade Synergistically Antagonize Exercise Fatigue in Rats under Simulated High Altitude
2013
Rapid ascent to high altitude causes illness and fatigue, and there is a demand for effective acute treatments to alleviate such effects. We hypothesized that increased oxygen delivery to the tissue using a combination of a hypertensive agent and an endothelin receptor A antagonist drugs would limit exercise-induced fatigue at simulated high altitude. Our data showed that the combination of 0.1 mg/kg ambrisentan with either 20 mg/kg ephedrine or 10 mg/kg methylphenidate significantly improved exercise duration in rats at simulated altitude of 4,267 m, whereas the individual compounds did not. In normoxic, anesthetized rats, ephedrine alone and in combination with ambrisentan increased heart…
Fabrication of quercetin and curcumin bionanovesicles for the prevention and rapid regeneration of full-thickness skin defects on mice
2013
In the present work biocompatible quercetin and curcumin nanovesicles were developed as a novel approach to prevent and restore skin tissue defects on chronic cutaneous pathologies. Stable and suitable quercetin- and curcumin-loaded phospholipid vesicles, namely liposomes and penetration enhancer-containing vesicles (PEVs), were prepared. Vesicles were made from a highly biocompatible mixture of phospholipids and alternatively a natural polyphenol, quercetin or curcumin. Liposomes were obtained by adding water, while PEVs by adding polyethylene glycol 400 and Oramix®CG110 to the water phase. Transmission electron microscopy, cryogenic-transmission electron microscopy and small- and wide-ang…
Roflumilast Prevents the Metabolic Effects of Bleomycin-Induced Fibrosis in a Murine Model
2015
Fibrotic remodeling is a process common to chronic lung diseases such as chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, acute respiratory distress syndrome and asthma. Based on preclinical studies phosphodiesterase 4 (PDE4) inhibitors may exhibit beneficial anti-inflammatory and anti-remodeling properties for the treatment of these respiratory disorders. Effects of PDE4 inhibitors on changes in the lung metabolome in models of pulmonary fibrotic remodeling have not yet been explored. This work studies the effects of the PDE4 inhibitor roflumilast on changes in the lung metabolome in the common murine model of bleomycin-induced lung fibrosis by nuclear magnetic resonance (…
Roflumilast, a phosphodiesterase 4 inhibitor, alleviates bleomycin-induced lung injury
2009
Mandarin translation of abstract Background and purpose: The effects of a phosphodiesterase 4 (PDE4) inhibitor, roflumilast, on bleomycin-induced lung injury were explored in ‘preventive’ and ‘therapeutic’ protocols and compared with glucocorticoids. Experimental approach: Roflumilast (1 and 5 mg·kg−1·d−1, p.o.) or dexamethasone (2.5 mg·kg−1·d−1, p.o.) was given to C57Bl/6J mice from day 1 to 14 (preventive) or day 7 to 21 (therapeutic) after intratracheal bleomycin (3.75 U·kg−1). In Wistar rats, roflumilast (1 mg·kg−1·d−1, p.o.) was compared with methylprednisolone (10 mg·kg−1·d−1, p.o.) from day 1 to 21 (preventive) or from day 10 to 21 (therapeutic), following intratracheal instillatio…
Both mature KIR+ and immature KIR- NK cells control pediatric acute B-cell precursor leukemia in NOD.Cg-Prkdcscid IL2rgtmWjl/Sz mice.
2014
Therapeutic natural killer (NK)-cell-mediated alloreactivity toward acute myeloid leukemia has largely been attributed to mismatches between killer immunoglobulin-like receptors (KIRs) on NK cells and their ligands, HLA class I molecules, on target cells. While adult acute B-cell precursor leukemia (BCP-ALL) appears to be resistant to NK-cell-mediated lysis, recent data indicate that pediatric BCP-ALL might yet be a target of NK cells. In this study, we demonstrate in a donor-patient-specific NOD.Cg-Prkdc(scid) IL2rg(tmWjl)/Sz (NSG) xenotransplantation model that NK cells mediate considerable alloreactivity toward pediatric BCP-ALL in vivo. Notably, both adoptively transferred mature KIR(+)…
Targeting components of the alternative NHEJ pathway sensitizes KRAS mutant leukemic cells to chemotherapy.
2014
Abstract Activating KRAS mutations are detected in a substantial number of hematologic malignancies. In a murine T-cell acute lymphoblastic leukemia (T-ALL) model, we previously showed that expression of oncogenic Kras induced a premalignant state accompanied with an arrest in T-cell differentiation and acquisition of somatic Notch1 mutations. These findings prompted us to investigate whether the expression of oncogenic KRAS directly affects DNA damage repair. Applying divergent, but complementary, genetic approaches, we demonstrate that the expression of KRAS mutants is associated with increased expression of DNA ligase 3α, poly(ADP-ribose) polymerase 1 (PARP1), and X-ray repair cross-comp…
Microenvironmental adaptation of experimental tumours to chronic vs acute hypoxia
2004
This study investigated long-term microenvironmental responses (oxygenation, perfusion, metabolic status, proliferation, vascular endothelial growth factor (VEGF) expression and vascularisation) to chronic hypoxia in experimental tumours. Experiments were performed using s.c.-implanted DS-sarcomas in rats. In order to induce more pronounced tumour hypoxia, one group of animals was housed in a hypoxic atmosphere (8% O(2)) for the whole period of tumour growth (chronic hypoxia). A second group was acutely exposed to inspiratory hypoxia for only 20 min prior to the measurements (acute hypoxia), whereas animals housed under normal atmospheric conditions served as controls. Acute hypoxia reduced…
Targeted disruption of the peroxisomal thiolase B gene in mouse: a new model to study disorders related to peroxisomal lipid metabolism
2004
The peroxisomal beta-oxidation system consists of four steps catalysed by three enzymes: acyl-CoA oxidase, 3-hydroxyacyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (multifunctional enzyme) and thiolase. In humans, thiolase activity is encoded by one gene, whereas in rodents, three enzymes encoded by three distinct genes (i.e. thiolase A, thiolase B and SCP2/thiolase) catalyse the thiolase activity. So far, acyl-CoA oxidase- and multifunctional enzyme-deficient patients have been identified and knock-out mice for these genes have been produced. Conversely, no isolated thiolase-deficient patient has been found, and no thiolase (A or B)-deficient mice have been generated. Hence, to better u…
Hybrid Chelator-Based PSMA Radiopharmaceuticals: Translational Approach
2021
(1) Background: Prostate-specific membrane antigen (PSMA) has been extensively studied in the last decade. It became a promising biological target in the diagnosis and therapy of PSMA-expressing cancer diseases. Although there are several radiolabeled PSMA inhibitors available, the search for new compounds with improved pharmacokinetic properties and simplified synthesis is still ongoing. In this study, we developed PSMA ligands with two different hybrid chelators and a modified linker. Both compounds have displayed a promising pharmacokinetic profile. (2) Methods: DATA5m.SA.KuE and AAZTA5.SA.KuE were synthesized. DATA5m.SA.KuE was labeled with gallium-68 and radiochemical yields of various…
Nitric oxide and brain hyperexcitability.
2004
Nitric oxide (NO) is a gaseous messenger involved in atypical forms of intercellular communications, able to exert a strong functional modulation of several neurotransmitter systems. In particular, NO heavily influences the excitatory neurotransmitter glutamate, mainly through NMDA receptors, and the inhibitory neurotransmitter GABA, mainly through GABA A receptors. Due to the involvement of glutamate and GABA in a delicate balance conditioning the functional status of the neural cells, this interaction suggests a role for NO in regulating neuronal excitability and its transition towards hyperexcitability phenomena. This article reviews the main knowledge about the relationships existing be…