scholarly journals Rodent animal models: from mild to advanced stages of diabetic nephropathy

2014 ◽  
Vol 22 (5) ◽  
pp. 279-293 ◽  
Author(s):  
Manpreet Kaur ◽  
Onkar Bedi ◽  
Shilpi Sachdeva ◽  
B. V. K. Krishna Reddy ◽  
Puneet Kumar
2016 ◽  
Vol 34 (4) ◽  
pp. 347-355 ◽  
Author(s):  
M. Omar Farooq ◽  
Ramon Bataller

Alcoholic liver disease (ALD) is a leading cause of liver-related morbidity and mortality. ALD encompasses a spectrum of disorders ranging from asymptomatic steatosis, alcoholic steatohepatitis, fibrosis, cirrhosis and its related complications. Moreover, patients can develop an acute-on-chronic form of liver failure called alcoholic hepatitis (AH). Most patients are diagnosed at advanced stages of the disease with higher rates of complications and mortality. The mainstream of therapy of ALD patients, regardless of the disease stage, is prolonged alcohol abstinence. The current therapeutic regimens for AH (i.e. prednisolone) have limited efficacy and targeted therapies are urgently needed. The development of such therapies requires translational studies in human samples and suitable animal models that reproduce clinical and histological features of AH. In recent years, new animal models that simulate some of the features of human AH have been developed, and translational studies using human samples have identified potential pathogenic factors and histological parameters that predict survival. In this review, we discuss the pathogenesis and management of ALD, focusing on AH, its current therapies and potential treatment targets.


Renal Failure ◽  
2015 ◽  
Vol 37 (9) ◽  
pp. 1529-1530 ◽  
Author(s):  
Kathryna F. Rodrigues ◽  
Nathália T. Pietrani ◽  
Adriana A. Bosco ◽  
Cláudia N. Ferreira ◽  
Valéria C. Sandrim ◽  
...  

2019 ◽  
Vol 317 (2) ◽  
pp. F399-F410 ◽  
Author(s):  
Jana Löwen ◽  
Elisabeth Gröne ◽  
Hermann-Josef Gröne ◽  
Wilhelm Kriz

As shown in our previous paper (Kriz W, Löwen J, Federico G, van den Born J, Gröne E, Gröne HJ. Am J Physiol Renal Physiol 312: F1101–F1111, 2017), mesangial matrix expansion in diabetic nephropathy (DN) results for a major part from the accumulation of worn-out undegraded glomerular basement membrane material. Here, based on the reevaluation of >900 biopsies of DN, we show that this process continues with the progression of the disease finally leading to the herniation of the matrix-overloaded tuft through the glomerular entrance to the outside. This leads to severe changes in the glomerular surroundings, including a dissociation of the juxtaglomerular apparatus with displacement of the macula densa. The herniation is associated with a prominent outgrowth of glomerular vessels from the tuft. Mostly, these aberrant vessels are an abnormal type of arteriole with frequent intramural insudations of plasma. They spread into glomerular surroundings extending in intertubular and periglomerular spaces. Their formation is associated with elevated mRNA levels of vascular endothelial growth factor-A, angiopoietins 1 and 2, and the corresponding receptors. Functionally, these processes seem to compromise tubuloglomerular feedback-related functions and may be one factor why Na+-glucose cotransporter-2 inhibitors are not effective in advanced stages of DN.


2020 ◽  
Vol 43 (5) ◽  
pp. 621-626
Author(s):  
Osaid Alser ◽  
Gehad Youssef ◽  
Simon Myers ◽  
Ali M. Ghanem

Abstract Background Microsurgery simulation is an important aspect of surgical training. Animal models have been widely used in simulation training, but they have some limitations including ethical restrictions, cost and availability. This has led to the use of synthetic models that can reduce reliance on animals in line with the 3R (refinement, reduction and replacement) principles. The aim of this paper was to evaluate the face validity of Surgitate™ three-in-one (artery, vein and nerve) silicone model. Methods Fourteen candidates performed one end-to-end anastomosis on artery, vein and nerve. The face validity of the vessel was assessed via questionnaires detailing their previous microsurgical experience and their feedback of using this model using the Likert scale. Data management and analysis were performed using IBM SPSS software (25.0). Results Participants tended to value this model in the earlier stages of microsurgical training particularly in the acquisition of basic microsurgical skills. It could be particularly useful in enhancing suturing skills as a replacement or reduction in the use of chicken models. The model has some drawbacks preluding its utilization into more advanced stages of surgical training. Further studies are needed to validate the model using more objective measures. Conclusion We present a novel synthetic model that can be potentially introduced to early stages of microsurgery training. The model would be ideal to meet the 3R principles of the use of animal models and as an alternative to the commonly used synthetic models. Level of evidence: Not ratable.


2014 ◽  
Vol 126 (4) ◽  
pp. 191-195 ◽  
Author(s):  
Boris Betz ◽  
Bryan R. Conway

Diabetes ◽  
1990 ◽  
Vol 39 (9) ◽  
pp. 1057-1063 ◽  
Author(s):  
R. Osterby ◽  
H.-H. Parving ◽  
E. Hommel ◽  
H. E. Jorgensen ◽  
H. Lokkegaard

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Kaichiro Sawada ◽  
Masao Toyoda ◽  
Noriko Kaneyama ◽  
Sawako Shiraiwa ◽  
Hitomi Moriya ◽  
...  

Background. Podocyte injury plays an important role in the onset and progression of diabetic nephropathy (DN). Downregulation ofα3β1-integrin expression in podocytes is thought to be associated with podocyte detachment from the glomerular basement membrane, although the mechanisms remain obscure. To determine the mechanism of podocyte detachment, we analyzed the expression levels ofα3β1-integrin in podocytes in early and advanced stages of DN.Methods. Surgical specimens from DN patients were examined byin situhybridization, and the expression levels ofα3- andβ1-integrin subunits in glomeruli of early (n=6) and advanced (n=8) stages were compared with those of normal glomeruli (n=5). Heat-sensitive mouse podocytes (HSMP) were cultured with TGF-β1 to reproduce the microenvironment of glomeruli of DN, and the expression levels of integrin subunits and the properties of migration and attachment were examined.Results. Podocytes of early-stage DN showed upregulation ofα3- andβ1-integrin expression while those of advanced stage showed downregulation. Real-time PCR indicated a tendency for upregulation ofα3- andβ1-integrin in HSMP cultured with TGF-β1. TGF-β1-stimulated HSMP also showed enhancedin vitromigration and attachment on collagen substrate.Conclusions. The results suggested that podocyte detachment during early stage of DN is mediated through upregulation ofα3β1-integrin.


Author(s):  
Laura Pérez-López ◽  
Mauro Boronat ◽  
Carlos Melián ◽  
Yeray Brito-Casillas ◽  
Ana M. Wägner

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1906 ◽  
Author(s):  
Francesca Fornari ◽  
Laura Gramantieri ◽  
Elisa Callegari ◽  
Ram C. Shankaraiah ◽  
Fabio Piscaglia ◽  
...  

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality. Molecular heterogeneity and absence of biomarkers for patient allocation to the best therapeutic option contribute to poor prognosis of advanced stages. Aberrant microRNA (miRNA) expression is associated with HCC development and progression and influences drug resistance. Therefore, miRNAs have been assayed as putative biomarkers and therapeutic targets. miRNA-based therapeutic approaches demonstrated safety profiles and antitumor efficacy in HCC animal models; nevertheless, caution should be used when transferring preclinical findings to the clinics, due to possible molecular inconsistency between animal models and the heterogeneous pattern of the human disease. In this context, models with defined genetic and molecular backgrounds might help to identify novel therapeutic options for specific HCC subgroups. In this review, we describe rodent models of HCC, emphasizing their representativeness with the human pathology and their usefulness as preclinical tools for assessing miRNA-based therapeutic strategies.


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