ANIMAL MODELS SIMULATING PATHOLOGICAL CONDITIONS: VARIOUS FORMS OF EXPERIMENTAL RENAL DISEASES

Abstracts ◽  
1977 ◽  
pp. 286
Author(s):  
Ramzi S. Cotran
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Domonkos Pap ◽  
Apor Veres-Székely ◽  
Beáta Szebeni ◽  
Réka Rokonay ◽  
Anna Ónody ◽  
...  

Abstract Background Recently, the role of IL-19, IL-20 and IL-24 has been reported in renal disorders. However, still little is known about their biological role. Methods Localization of IL-20RB was determined in human biopsies and in the kidneys of mice that underwent unilateral ureteral obstruction (UUO). Renal Il19, Il20 and Il24 expression was determined in ischemia/reperfusion, lipopolysaccharide, streptozotocin, or UUO induced animal models of kidney diseases. The effects of H2O2, LPS, TGF-β1, PDGF-B and IL-1β on IL19, IL20 and IL24 expression was determined in peripheral blood mononuclear cells (PBMCs). The extents of extracellular matrix (ECM) and α-SMA, Tgfb1, Pdgfb, and Ctgf expression were determined in the kidneys of Il20rb knockout (KO) and wild type (WT) mice following UUO. The effect of IL-24 was also examined on HK-2 tubular epithelial cells and NRK49F renal fibroblasts. Results IL-20RB was present in the renal biopsies of patients with lupus nephritis, IgA and diabetic nephropathy. Amount of IL-20RB increased in the kidneys of mice underwent UUO. The expression of Il19, Il20 and Il24 increased in the animal models of various kidney diseases. IL-1β, H2O2 and LPS induced the IL19, IL20 and IL24 expression of PBMCs. The extent of ECM, α-SMA, fibronectin, Tgfb1, Pdgfb, and Ctgf expression was lower in the kidney of Il20rb KO compared to WT mice following UUO. IL-24 treatment induced the apoptosis and TGF-β1, PDGF-B, CTGF expression of HK-2 cells. Conclusions Our data confirmed the significance of IL-19, IL-20 and IL-24 in the pathomechanism of renal diseases. Furthermore, we were the first to demonstrate the pro-fibrotic effect of IL-24.


1983 ◽  
Vol 92 (6_suppl) ◽  
pp. 24-25
Author(s):  
E. N. Myers ◽  
Q. C. Beery ◽  
C. D. Bluestone ◽  
M. B. Möller ◽  
B. A. Sigler ◽  
...  

The management of patients with middle ear disease should be based on an understanding of the pathogenesis of the disease and its course. In this group of investigations, patients with pathological conditions such as cleft palate, which affects ET function, are studied. Animal models are then developed to simulate the clinical condition, thus providing a method of isolating the variables.


2018 ◽  
Vol 14 (4) ◽  
pp. 246-264 ◽  
Author(s):  
Christophe Sirac ◽  
Guillermo A. Herrera ◽  
Paul W. Sanders ◽  
Vecihi Batuman ◽  
Sebastien Bender ◽  
...  

2000 ◽  
Vol 23 (2) ◽  
pp. 97-103 ◽  
Author(s):  
B. Andreini ◽  
V. Panichi ◽  
C. Cirami ◽  
M. Migliori ◽  
S. DE Pietro ◽  
...  

Background Anti-neutrophil cytoplasmic autoantibodies (ANCA) have been described in patients suffering from systemic vasculitis such as Wegener granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and other pathological conditions. In this paper we report a greater incidence of ANCA in hemodialysis patients as compared to peritoneal dialysis patients, predialytic uremic patients and non-renal patients; a possible role for dialysis bioincompatibility in ANCA generation was also investigated. Methods A total of 335 uremics in substitutive treatment (176 in hemodialytic treatment and 159 in peritoneal dialysis) were examined for ANCA positivity. A total of 189 patients with advanced renal failure in conservative treatment and 100 healthy subjects were used as control. The dialysis techniques were standard hemodialysis (n = 119), low volume hemodiafiltration (n = 26) and hemofiltration (n = 31). ANCA positivity was examined by immunofluorescence (IF): diffuse finely granular staining was considered as classical positive reaction (C-ANCA) and P-ANCA was diagnosed if a perinuclear staining was observed. EIA for proteinase-3 (anti PR-3) and myeloperoxidase-antibodies (anti-MPO) were also performed. Results In non-renal patients and in patients with pre-dialytic renal insufficiency none were found ANCA positive. In peritoneal dialysis patients all but one were ANCA negative with IF, with all EIA test resulting negative. In hemodialytic patients, a positive IF test was found in 26 (14.7%) for P-ANCA and in 5 (2.8%) for C-ANCA; using the EIA test 23 (13%) patients were positive for MPO and 12 (6.8%) for PR-3. Conclusions No correlation with age, primary renal diseases, dialytic age, dialysis membrane materials was found; regarding the different extracorporeal dialytic techniques a higher incidence (p < 0.02) was detected in patients undergoing HDF. Backfiltration of contaminated dialysate may induce ANCA via an increased cytokine generation. (Int J Artif Organs 2000; 23: 97–103)


2016 ◽  
Vol 310 (2) ◽  
pp. F109-F118 ◽  
Author(s):  
Kirti Bhatt ◽  
Mitsuo Kato ◽  
Rama Natarajan

MicroRNAs (miRNA) are endogenously produced short noncoding regulatory RNAs that can repress gene expression by posttranscriptional mechanisms. They can therefore influence both normal and pathological conditions in diverse biological systems. Several miRNAs have been detected in kidneys, where they have been found to be crucial for renal development and normal physiological functions as well as significant contributors to the pathogenesis of renal disorders such as diabetic nephropathy, acute kidney injury, lupus nephritis, polycystic kidney disease, and others, due to their effects on key genes involved in these disease processes. miRNAs have also emerged as novel biomarkers in these renal disorders. Due to increasing evidence of their actions in various kidney segments, in this mini-review we discuss the functional significance of altered miRNA expression during the development of renal pathologies and highlight emerging miRNA-based therapeutics and diagnostic strategies for early detection and treatment of kidney diseases.


2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Hamid Tayebi Khosroshahi ◽  
Behzad Abedi ◽  
Sabalan Daneshvar ◽  
Yashar Sarbaz ◽  
Abolhassan Shakeri Bavil

At the present time, imaging guided renal biopsy is used to provide diagnoses in most types of primary and secondary renal diseases. It has been claimed that renal biopsy can provide a link between diagnosis of renal disease and its pathological conditions. However, sometimes there is a considerable mismatch between patient renal outcome and pathological findings in renal biopsy. This is the time to address some new diagnostic methods to resolve the insufficiency of conventional percutaneous guided renal biopsy. Nanotechnology is still in its infancy in renal imaging; however, it seems that it is the next step in renal biopsy, providing solutions to the limitations of conventional modalities.


2021 ◽  
pp. 0271678X2098456
Author(s):  
Takahiko Imai ◽  
Hirofumi Matsubara ◽  
Hideaki Hara

Intracranial hemorrhage (ICH) is a devastating disease which induces high mortality and poor outcomes including severe neurological dysfunctions. ICH pathology is divided into two types: primary brain injury (PBI) and secondary brain injury (SBI). Although there are numerous preclinical studies documenting neuroprotective agents in experimental ICH models, no effective drugs have been developed for clinical use due to complicated ICH pathology. Oxidative and inflammatory stresses play central roles in the onset and progression of brain injury after ICH, especially SBI. Nrf2 is a crucial transcription factor in the anti-oxidative stress defense system. Under normal conditions, Nrf2 is tightly regulated by the Keap1. Under ICH pathological conditions, such as overproduction of reactive oxygen species (ROS), Nrf2 is translocated into the nucleus where it up-regulates the expression of several anti-oxidative phase II enzymes such as heme oxygenase-1 (HO-1). Recently, many reports have suggested the therapeutic potential of Nrf2 activators (including natural or synthesized compounds) for treating neurodegenerative diseases. Moreover, several Nrf2 activators attenuate ischemic stroke-induced brain injury in several animal models. This review summarizes the efficacy of several Nrf2 activators in ICH animal models. In the future, Nrf2 activators might be approved for the treatment of ICH patients.


Author(s):  
Maciej Fijałkowski ◽  
Joanna Stępniewska ◽  
Maciej Domański ◽  
Kazimierz Ciechanowski ◽  
Edyta Golembiewska

Eicosanoids are biologically active molecules that are created in the process of oxidation of arachidonic acid (AA) which is a constituent of the cell membrane phospholipids. Throughout the years it was evidenced by experiments that the lipid and lipid-derived metabolites play an important role in physiological and pathological processes in the kidneys. They are being considered as biomarkers in detecting acute kidney injury, nephrotoxicity, glomerulonephritis and early stages of diabetic nephropathy because of their participation in inflammatory processes and in oxidative stress. They might be also considered as potential novel targets of therapy. However, the role of eicosanoids is still not fully clear and needs to be explored in future studies. In this brief review, studies on the role of eicosanoids in physiological and pathological conditions, e.g. acute kidney injury (AKI) and chronic kidney disease (CKD), and in different renal replacement therapies, including kidney transplantation, are being discussed.


2022 ◽  
Author(s):  
Shuai Chen ◽  
Jinling Liao ◽  
Yang Chen ◽  
Yufang Lv ◽  
Qiong Song ◽  
...  

Abstract Multiple studies have been performed to map the kidney landscape of human and rodent, along with the development of sequencing technique. Although rodent disease models have been widely applied, many disadvantages also exist. Non-human primates (NHPs) are considered as the closest experimental animals to humans and show great advantages in the construction of animal models of human disease. Therefore, a comprehensive understanding of the heterogeneity and homogeneity between human and multiple animal kidney cells is important for further establishing animal models of human renal disease. Here, we generated the first single-cell transcriptome data of normal adult cynomolgus monkey kidney using 10x Genomics scRNA-seq platform. Then, we further performed an in-depth comparison across species at the single-cell level, and our analysis indicated that the gene expression of adult primate kidney cells showed a better correlation with human kidney than mouse kidney. Furthermore, our results demonstrated that the cellular localization of GWAS-identified renal disease genes showed differences across species. The cellular localization of blood pressure associated genes in human displayed similarity to cynomolgus monkey. This study provided a reliable reference for further studies associated with renal diseases on NHPs. In addition, our results also provided a novel insight into the choice of renal disease animal model and a detailed explanation for close genetic relationship between NHPs and human at a single cell level.


2021 ◽  
pp. 1-17
Author(s):  
Hai Ning Wee ◽  
Jian-Jun Liu ◽  
Jianhong Ching ◽  
Jean-Paul Kovalik ◽  
Su Chi Lim

<b><i>Background:</i></b> The kynurenine pathway (KP) is the major catabolic pathway for tryptophan degradation. The KP plays an important role as the sole de novo nicotinamide adenine dinucleotide (NAD<sup>+</sup>) biosynthetic pathway in normal human physiology and functions as a counter-regulatory mechanism to mitigate immune responses during inflammation. Although the KP has been implicated in a variety of disorders including Huntington’s disease, seizures, cardiovascular disease, and osteoporosis, its role in renal diseases is seldom discussed. <b><i>Summary:</i></b> This review summarizes the roles of the KP and its metabolites in acute kidney injury (AKI) and chronic kidney disease (CKD) based on current literature evidence. Metabolomics studies demonstrated that the KP metabolites were significantly altered in patients and animal models with AKI or CKD. The diagnostic and prognostic values of the KP metabolites in AKI and CKD were highlighted in cross-sectional and longitudinal human observational studies. The biological impact of the KP on the pathophysiology of AKI and CKD has been studied in experimental models of different etiologies. In particular, the activation of the KP was found to confer protection in animal models of glomerulonephritis, and its immunomodulatory mechanism may involve the regulation of T cell subsets such as Th17 and regulatory T cells. Manipulation of the KP to increase NAD<sup>+</sup> production or diversion toward specific KP metabolites was also found to be beneficial in animal models of AKI. <b><i>Key Messages:</i></b> KP metabolites are reported to be dysregulated in human observational and animal experimental studies of AKI and CKD. In AKI, the magnitude and direction of changes in the KP depend on the etiology of the damage. In CKD, KP metabolites are altered with the onset and progression of CKD all the way to advanced stages of the disease, including uremia and its related vascular complications. The activation of the KP and diversion to specific sub-branches are currently being explored as therapeutic strategies in these diseases, especially with regards to the immunomodulatory effects of certain KP metabolites. Further elucidation of the KP may hold promise for the development of biomarkers and targeted therapies for these kidney diseases.


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