From the Preclinical Model to the Patient

2008 ◽  
pp. 70-85 ◽  
Author(s):  
Ernst B. Hunziker
Keyword(s):  
Preclinical Model

2056-P: In Vivo Human Islet Compensation and Dysfunction to Diet-Induced Obesity: A Phase 0 Preclinical Model

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 2056-P
Author(s):  
JULIE A. KERR-CONTE ◽  
JULIEN THEVENET ◽  
GIANNI PASQUETTI ◽  
PAULINE PETIT ◽  
CLARA CLABAUT ◽  
...  
Keyword(s):  
Human Islet ◽  
Preclinical Model ◽  
Diet Induced Obesity ◽  
Phase 0

scholarly journals In Preclinical Model of Ovarian Cancer, the SGK1 Inhibitor SI113 Counteracts the Development of Paclitaxel Resistance and Restores Drug Sensitivity

2019 ◽  
Vol 12 (8) ◽  
pp. 1045-1055 ◽  
Author(s):  
Lucia D'Antona ◽  
Vincenzo Dattilo ◽  
Giada Catalogna ◽  
Domenica Scumaci ◽  
Claudia Vincenza Fiumara ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Sensitivity ◽  
Preclinical Model ◽  
Paclitaxel Resistance

scholarly journals NeuroHeal Improves Muscle Regeneration after Injury

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 22
Author(s):  
Sara Marmolejo-Martínez-Artesero ◽  
David Romeo-Guitart ◽  
Vanesa Venegas ◽  
Mario Marotta ◽  
Caty Casas
Keyword(s):  
Satellite Cell ◽  
Muscle Regeneration ◽  
Cell Biology ◽  
Fiber Type ◽  
Traumatic Injury ◽  
Injury Rate ◽  
Scar Tissue ◽  
Medical Problem ◽  
Preclinical Model

Musculoskeletal injuries represent a challenging medical problem. Although the skeletal muscle is able to regenerate and recover after injury, the process engaged with conservative therapy can be inefficient, leading to a high re-injury rate. In addition, the formation of scar tissue implies an alteration of mechanical properties in muscle. There is still a need for new treatments of the injured muscle. NeuroHeal may be one option. Published studies demonstrated that it reduces muscle atrophy due to denervation and disuse. The main objective of the present work was to assess the potential of NeuroHeal to improve muscle regeneration after traumatic injury. Secondary objectives included characterizing the effect of NeuroHeal treatment on satellite cell biology. We used a rat model of sport-induced injury in the gastrocnemius and analyzed the effects of NeuroHeal on functional recovery by means of electrophysiology and tetanic force analysis. These studies were accompanied by immunohistochemistry of the injured muscle to analyze fibrosis, satellite cell state, and fiber type. In addition, we used an in vitro model to determine the effect of NeuroHeal on myoblast biology and partially decipher its mechanism of action. The results showed that NeuroHeal treatment advanced muscle fiber recovery after injury in a preclinical model of muscle injury, and significantly reduced the formation of scar tissue. In vitro, we observed that NeuroHeal accelerated the formation of myotubes. The results pave the way for novel therapeutic avenues for muscle/tendinous disorders.

scholarly journals Treatment potential of LPCN 1144 on liver health and metabolic regulation in a non-genomic, high fat diet induced NASH rabbit model

2021 ◽  
Author(s):  
P. Comeglio ◽  
E. Sarchielli ◽  
S. Filippi ◽  
I. Cellai ◽  
G. Guarnieri ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
High Fat Diet ◽  
Metabolic Regulation ◽  
Therapeutic Potential ◽  
Rabbit Model ◽  
Free Testosterone ◽  
Preclinical Model ◽  
High Fat ◽  
Liver Health ◽  
Metabolic Dysfunctions

Abstract Purpose Low free testosterone (T) level in men is independently associated with presence and severity of Non-Alcoholic Steatohepatitis (NASH). The histological and molecular effects of oral testosterone prodrug LPCN 1144 treatment on hepatic fibrosis and NASH features are unknown. A metabolic syndrome-induced NASH model in rabbits consuming high fat diet (HFD) has been previously used to assess treatment effects of injectable T on hepatic fibrosis and NASH features. Here we present results on LPCN 1144 in this HFD-induced, NASH preclinical model. Methods Male rabbits were randomly assigned to five groups: regular diet (RD), HFD, HFD + 1144 vehicle (HFD + Veh), HFD + 1144 (1144), and HFD + 1144 + α-tocopherol (1144 + ALPHA). Rabbits were sacrificed after 12 weeks for liver histological, biochemical and genetic analyses. Histological scores were obtained through Giemsa (inflammation), Masson’s trichrome (steatosis and ballooning), and Picrosirius Red (fibrosis) staining. Results Compared to RD, HFD and HFD + Veh significantly worsened NASH features and hepatic fibrosis. Considering HFD and HFD + Veh arms, histological and biomarker features were not significantly different. Both 1144 and 1144 + ALPHA arms improved mean histological scores of NASH as compared to HFD arm. Importantly, percentage of fibrosis was improved in both 1144 (p < 0.05) and 1144 + ALPHA (p = 0.05) treatment arms vs. HFD. Both treatment arms also reduced HFD-induced inflammation and fibrosis mRNA markers. Furthermore, 1144 treatments significantly improved HFD-induced metabolic dysfunctions. Conclusions Histological and biomarker analyses demonstrate that LPCN 1144 improved HFD-induced hepatic fibrosis and NASH biochemical, biomolecular and histochemical features. These preclinical findings support a therapeutic potential of LPCN 1144 in the treatment of NASH and of hepatic fibrosis.

Discovery of a Potent and Selective Axl Inhibitor in Preclinical Model

2021 ◽  
pp. 116137
Author(s):  
Satoshi Inoue ◽  
Yoshinobu Yamane ◽  
Shuntaro Tsukamoto ◽  
Hiroshi Azuma ◽  
Satoshi Nagao ◽  
...  
Keyword(s):  
Preclinical Model

scholarly journals Esmolol during cardiopulmonary resuscitation reduces neurological injury in a porcine model of cardiac arrest

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Laura Ruggeri ◽  
Francesca Nespoli ◽  
Giuseppe Ristagno ◽  
Francesca Fumagalli ◽  
Antonio Boccardo ◽  
...  
Keyword(s):  
Cardiopulmonary Resuscitation ◽  
Porcine Model ◽  
Neuronal Degeneration ◽  
Neuron Specific Enolase ◽  
Coronary Perfusion Pressure ◽  
Neurological Injury ◽  
Saline Control ◽  
Preclinical Model ◽  
Coronary Perfusion ◽  
To Receive

AbstractPrimary vasopressor efficacy of epinephrine during cardiopulmonary resuscitation (CPR) is due to its α-adrenergic effects. However, epinephrine plays β1-adrenergic actions, which increasing myocardial oxygen consumption may lead to refractory ventricular fibrillation (VF) and poor outcome. Effects of a single dose of esmolol in addition to epinephrine during CPR were investigated in a porcine model of VF with an underlying acute myocardial infarction. VF was ischemically induced in 16 pigs and left untreated for 12 min. During CPR, animals were randomized to receive epinephrine (30 µg/kg) with either esmolol (0.5 mg/kg) or saline (control). Pigs were then observed up to 96 h. Coronary perfusion pressure increased during CPR in the esmolol group compared to control (47 ± 21 vs. 24 ± 10 mmHg at min 5, p < 0.05). In both groups, 7 animals were successfully resuscitated and 4 survived up to 96 h. No significant differences were observed between groups in the total number of defibrillations delivered prior to final resuscitation. Brain histology demonstrated reductions in cortical neuronal degeneration/necrosis (score 0.3 ± 0.5 vs. 1.3 ± 0.5, p < 0.05) and hippocampal microglial activation (6 ± 3 vs. 22 ± 4%, p < 0.01) in the esmolol group compared to control. Lower circulating levels of neuron specific enolase were measured in esmolol animals compared to controls (2[1–3] vs. 21[16–52] ng/mL, p < 0.01). In this preclinical model, β1-blockade during CPR did not facilitate VF termination but provided neuroprotection.

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