scholarly journals Scarless repair of acute and chronic kidney injury in African Spiny mice (Acomys cahirinus)

2018 ◽  
Author(s):  
Daryl M. Okamura ◽  
Chris M. Brewer ◽  
Paul Wakenight ◽  
Nadia Bahrami ◽  
Kristina Bernardi ◽  
...  
Keyword(s):  
Wound Repair ◽  
Kidney Injury ◽  
Organ Injury ◽  
Solid Organ ◽  
Internal Organs ◽  
Terrestrial Mammals ◽  
Medical Care Costs ◽  
Spiny Mice ◽  
Muroid Rodents ◽  
And Function

SummarySolid organ fibrosis is a major burden on global health and medical care costs. Muroid rodents of the genus Acomys (African Spiny mice) are terrestrial mammals that evolved remarkable abilities to regenerate severe skin wounds without scar formation. However, whether scar-free wound repair in Acomys extends beyond skin to vital internal organs is not known. Here, we used two aggressive kidney injury models known to produce severe renal fibrosis and show that despite equivalent acute kidney injury, there was rapid restoration of nephron structure and function without fibrosis in Acomys compared to extensive fibrosis leading to renal failure in Mus musculus. These results suggest Acomys species have evolved genomic adaptations for wound healing that activate regenerative repair pathways not only in skin, but also in vital internal organs. Our findings have important implications for discovering a long-sought evolutionary solution to internal organ injury and regeneration.

scholarly journals Serial hemoglobin monitoring in adult patients with blunt solid organ injury: less is more

2020 ◽  
Vol 5 (1) ◽  
pp. e000446 ◽  
Author(s):  
Firas Madbak ◽  
Dustin Price ◽  
David Skarupa ◽  
Brian Yorkgitis ◽  
David Ebler ◽  
...  
Keyword(s):  
Injury Severity ◽  
Kidney Injury ◽  
Hemodynamic Instability ◽  
Organ Injury ◽  
Solid Organ ◽  
Solid Organ Injury ◽  
Level Of Evidence ◽  
Less Is More ◽  
Urban Level ◽  
Level 1 Trauma Center

BackgroundPatients who sustain blunt solid organ injury to the liver, spleen, or kidney and are treated nonoperatively frequently undergo serial monitoring of their hemoglobin (Hb). We hypothesized that among initially hemodynamically stable patients with blunt splenic, hepatic, or renal injuries treated without an operation, scheduled monitoring of serum Hb values may be unnecessary as hemodynamic instability, not merely Hb drop, would prompt intervention.MethodsWe performed a retrospective review of patients admitted to our urban Level 1 trauma center following blunt trauma with any grade III, IV, or V liver, spleen, or kidney injury from January 1, 2016 to December 31, 2016. Patients who were hemodynamically unstable and went directly to the operating room or interventional radiology were excluded. Patients who required any urgent or unplanned operative or angiographic intervention were compared with patients who did not require an intervention. Routine demographic and outcome variables were obtained and bivariate and multivariate regression statistics were performed using Stata V.10.ResultsA total of 138 patients were included in the study. Age (39.3 vs 41.4, p=0.51), mean injury severity score (26.7 vs 22.1, p=0.12), and admission Hb (11.9 vs 12.8, p=0.06) did not differ significantly between the two groups. The number of Hb draws (9.2 vs 10, p=0.69) and the associated change in Hb (3.7 vs 3.5, p=0.71) did not differ significantly between the two groups. Only splenic grade predicted need for urgent intervention (3.5 vs 2, p<0.001). All patients who required an operative or radiologic intervention did so based on change in hemodynamics or severity of splenic grade, per our institutional protocol, and not Hb trend.DiscussionAmong patients with blunt solid organ injury, a need for emergent intervention in the form of laparotomy or angioembolization occurs within the first hours of injury. Routine scheduled Hb measurements did not change management in our cohort.Level of evidenceLevel III.

scholarly journals Salvia miltiorrhizaInjection Ameliorates Renal Damage Induced by Lead Exposure in Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Lei Li ◽  
Yuanyuan Zhang ◽  
Juanjuan Ma ◽  
Weichong Dong ◽  
Qiongtao Song ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Salvia Miltiorrhiza ◽  
Kidney Injury ◽  
Serum Levels ◽  
Organ Injury ◽  
Therapeutic Drug ◽  
High Dose ◽  
Protective Effects ◽  
Pb Accumulation ◽  
And Function

Exposure to lead (Pb) can induce kidney injury and our recent studies have found thatSalvia miltiorrhiza(SM) injection, a traditional Chinese medicine, could protect against the organ injury induced by iron overload. This study was designed to investigate the protective effects of SM injection on nephrotoxicity induced by Pb acetate in mice and to elucidate the potential mechanism(s). Healthy male mice were randomly divided into four groups: control, Pb, low-doseSalvia miltiorrhiza(L-SM), and high-doseSalvia miltiorrhiza(H-SM). SM injection dose dependently reduced the Pb accumulation in the kidney, decreased kidney coefficients, and ameliorated renal structure and function from the morphology analysis. Meanwhile, SM administration downregulated serum levels of blood urea nitrogen (BUN) and creatinine (CR), decreased malondialdehyde (MAD) content, and increased activities of super oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the kidney homogenate. Moreover, SM injection reduced the level of renal apoptosis by immunohistochemical staining analysis. Our findings implicate the therapeutic potential of SM injection for Pb-induced nephrotoxicity, which were at least partly due to the decrease of Pb accumulation, inhibition of lipid peroxidation, and suppression of renal apoptosis. These results provided preliminary experimental support for Danshen as a therapeutic drug for Pb poisoning diseases.

scholarly journals Abdominal Pain, Hyperkalemia, and Elevated Creatinine after Blunt Trauma: Bladder Rupture and Pseudo–Acute-Kidney-Injury.

2018 ◽  
Vol 13 (2) ◽  
Author(s):  
Reza D Mirza ◽  
Eric KC Wong ◽  
Robert Yang ◽  
Catherine Clase
Keyword(s):  
Acute Kidney Injury ◽  
Abdominal Pain ◽  
Kidney Injury ◽  
Organ Injury ◽  
Bladder Rupture ◽  
Free Fluid ◽  
Solid Organ ◽  
Solid Organ Injury ◽  
Elevated Creatinine ◽  
Initial Imaging

A 40-year-old man involved in trauma presented with abdominal pain and ascites. He was referred to nephrology for elevated creatinine and hyperkalemia. Initial imaging showed diffuse free fluid in the abdomen and pelvis without solid organ injury. Paracentesis drained 1.5L of yellow fluid notable for a creatinine of 2259 μmol/L. Intraperitoneal urinary bladder rupture was diagnosed and surgically repaired. Within 24 hours, creatinine had normalized consistent with a presentation of pseudo-acute-kidney-injury. This case and a literature review reveals that this condition is often delayed in diagnosis or misdiagnosed altogether. 

scholarly journals The critical roles of histone deacetylase 3 in the pathogenesis of solid organ injury

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Li Ning ◽  
Xiong Rui ◽  
Wang Bo ◽  
Geng Qing
Keyword(s):  
Histone Deacetylase ◽  
Chromatin Remodeling ◽  
Current Knowledge ◽  
Organ Injury ◽  
Solid Organ ◽  
Solid Organ Injury ◽  
Histone Deacetylase 3 ◽  
Physiological Conditions ◽  
Inflammatory Conditions ◽  
Therapeutic Value

AbstractHistone deacetylase 3 (HDAC3) plays a crucial role in chromatin remodeling, which, in turn, regulates gene transcription. Hence, HDAC3 has been implicated in various diseases, including ischemic injury, fibrosis, neurodegeneration, infections, and inflammatory conditions. In addition, HDAC3 plays vital roles under physiological conditions by regulating circadian rhythms, metabolism, and development. In this review, we summarize the current knowledge of the physiological functions of HDAC3 and its role in organ injury. We also discuss the therapeutic value of HDAC3 in various diseases.

scholarly journals Management for traumatic hepatic injury diagnosed by contrast-enhanced ultrasonography in a patient with an occluded coeliac axis: a case report

2021 ◽  
Vol 49 (6) ◽  
pp. 030006052110199
Author(s):  
Young Hoon Sul ◽  
Yook Kim
Keyword(s):  
Case Report ◽  
Hepatic Artery ◽  
Hepatic Injury ◽  
Active Bleeding ◽  
Organ Injury ◽  
Solid Organ ◽  
Median Arcuate Ligament ◽  
Contrast Enhanced ◽  
Arcuate Ligament ◽  
Contrast Enhanced Ultrasonography

Transcatheter arterial embolization (TAE) is the standard of care for haemodynamically-stable patients with blunt hepatic injury but it is sometimes impossible due to unfavourable vascular anatomies. This case report describes a 43-year-old male patient with abdominal pain following a motorcycle accident. Based on computed tomography (CT) findings, he was diagnosed with high-grade hepatic injury with coeliac axis stenosis (CAS) due to compression by the median arcuate ligament, and an aberrant right hepatic artery. Contrast-enhanced ultrasonography (CEUS) demonstrated multiple high echogenic tubular and ovoid structures suggestive of active bleeding within the injured liver area. Angiography revealed unique interlobar and intrahepatic collateral vessels between the right and left hepatic arteries. Liver haemorrhages were also identified. Catheterization of the feeding arteries through the collateral pathway was unsuccessful, so a decision was made to cannulate the stenotic portion of the coeliac trunk with a 5-Fr Yashiro catheter. After several attempts, the microcatheter was successfully advanced coaxially into the common hepatic artery. Embolization was performed with a 1:2 mixture of N-butyl cyanoacrylate and iodized oil. Successful haemostasis was confirmed following TAE. CEUS helped clinicians identify active bleeding following traumatic solid organ injury. TAE was a safe and effective treatment strategy. Before performing TAE, attention should be given to the presence of CAS associated with compression by the median arcuate ligament.

scholarly journals Extracellular vesicles as mediators and markers of acute organ injury: current concepts

2021 ◽  
Author(s):  
Birte Weber ◽  
Niklas Franz ◽  
Ingo Marzi ◽  
Dirk Henrich ◽  
Liudmila Leppik
Keyword(s):  
Extracellular Vesicles ◽  
Inflammatory Diseases ◽  
Organ Injury ◽  
Isolation And Characterization ◽  
Communication Processes ◽  
Incidence And Mortality ◽  
New Biomarkers ◽  
And Function

AbstractDue to the continued high incidence and mortality rate worldwide, there is a need to develop new strategies for the quick, precise, and valuable recognition of presenting injury pattern in traumatized and poly-traumatized patients. Extracellular vesicles (EVs) have been shown to facilitate intercellular communication processes between cells in close proximity as well as distant cells in healthy and disease organisms. miRNAs and proteins transferred by EVs play biological roles in maintaining normal organ structure and function under physiological conditions. In pathological conditions, EVs change the miRNAs and protein cargo composition, mediating or suppressing the injury consequences. Therefore, incorporating EVs with their unique protein and miRNAs signature into the list of promising new biomarkers is a logical next step. In this review, we discuss the general characteristics and technical aspects of EVs isolation and characterization. We discuss results of recent in vitro, in vivo, and patients study describing the role of EVs in different inflammatory diseases and traumatic organ injuries. miRNAs and protein signature of EVs found in patients with acute organ injury are also debated.

scholarly journals Surgical procedures suppress autophagic flux in the kidney

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Carolyn N. Brown ◽  
Daniel Atwood ◽  
Deepak Pokhrel ◽  
Sara J. Holditch ◽  
Christopher Altmann ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Mammalian Target Of Rapamycin ◽  
Kidney Injury ◽  
Compensatory Hypertrophy ◽  
Autophagic Flux ◽  
Bafilomycin A1 ◽  
Concomitant Increase ◽  
Sham Surgery ◽  
And Function ◽  
Pro Inflammatory Cytokines

AbstractMany surgical models are used to study kidney and other diseases in mice, yet the effects of the surgical procedure itself on the kidney and other tissues have not been elucidated. In the present study, we found that both sham surgery and unilateral nephrectomy (UNX), which is used as a model of renal compensatory hypertrophy, in mice resulted in increased mammalian target of rapamycin complex 1/2 (mTORC1/2) in the remaining kidney. mTORC1 is known to regulate lysosomal biogenesis and autophagy. Genes associated with lysosomal biogenesis and function were decreased in sham surgery and UNX kidneys. In both sham surgery and UNX, there was suppressed autophagic flux in the kidney as indicated by the lack of an increase in LC3-II or autophagosomes seen on immunoblot, IF and EM after bafilomycin A1 administration and a concomitant increase in p62, a marker of autophagic cargo. There was a massive increase in pro-inflammatory cytokines, which are known to activate ERK1/2, in the serum after sham surgery and UNX. There was a large increase in ERK1/2 in sham surgery and UNX kidneys, which was blocked by the MEK1/2 inhibitor, trametinib. Trametinib also resulted in a significant decrease in p62. In summary, there was an intense systemic inflammatory response, an ERK-mediated increase in p62 and suppressed autophagic flux in the kidney after sham surgery and UNX. It is important that researchers are aware that changes in systemic pro-inflammatory cytokines, ERK1/2 and autophagy can be caused by sham surgery as well as the kidney injury/disease itself.

scholarly journals Cytomegalovirus in urinary sediment in patients with acute kidney injury

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sahra Pajenda ◽  
Sebastian Kapps ◽  
Daniela Gerges ◽  
Gregor Hoermann ◽  
Ludwig Wagner ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Allograft ◽  
Quantitative Polymerase Chain Reaction ◽  
Rna Extraction ◽  
Kidney Injury ◽  
Solid Organ ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Urine Sediment ◽  
Urinary Sediment

Abstract Background Immunosuppression in solid organ transplantation is associated with frequent infections. Renal allograft recipients are susceptible to opportunistic infections and can acquire human cytomegalovirus (HCMV) infections even within the allograft. There, HCMV can be found in both the glomerulus and tubular cells, but is mostly restricted to specific and circumscribed sites. Therefore, not all organ infections are identifiable by immunohistology for HCMV proteins in fine needle core biopsies. Thus, we performed a urinalysis study to search for HCMV-specific RNA transcripts in the urine sediment of patients with acute kidney injury. Methods Urinary sediment of 90 patients with acute kidney injury (AKI), including 48 renal transplant recipients (RTX) and 42 non-transplant recipients (nRTX), was collected from morning urine for RNA extraction and reverse transcription. The copy number of HCMV transcripts was evaluated using a UL132 HCMV-specific probe set and by real-time quantitative polymerase chain reaction (RT-qPCR). Results Of the 48 RTX patients, ten showed HCMV copies in their urine sediment cells. Within this group, three recipients had negative HCMV serology and received an allograft from an HCMV-seropositive donor. In addition, all three RTX patients on a belatacept-based immunosuppressive regimen had HCMV transcripts in their urine. Of the 42 nRTX patients, only two had detectable HCMV transcripts in urine sediment cells and both were under immunosuppression. Conclusions Ten immunosuppressed renal allograft recipients and two immunosuppressed non-transplant patients with AKI showed HCMV copies in urine sediment. Thus, HCMV positivity in urinary sediment appears to be associated with immunosuppression. This study describes a novel noninvasive method for detection of HCMV in urinary sediment. Whether all HCMV infections can be detected or only those with viral replication warrants further investigation.

scholarly journals Proteolytic Events of Wound-Healing — Coordinated Interactions Among Matrix Metalloproteinases (MMPs), Integrins, and Extracellular Matrix Molecules

2001 ◽  
Vol 12 (5) ◽  
pp. 373-398 ◽  
Author(s):  
Bjorn Steffensen ◽  
Lari Häkkinen ◽  
Hannu Larjava
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Matrix Metalloproteinases ◽  
Wound Repair ◽  
Enzyme Activation ◽  
Processing Enzymes ◽  
The Matrix ◽  
Signaling Receptors ◽  
State Of Rest ◽  
And Function

During wound-healing, cells are required to migrate rapidly into the wound site via a proteolytically generated pathway in the provisional matrix, to produce new extracellular matrix, and, subsequently, to remodel the newly formed tissue matrix during the maturation phase. Two classes of molecules cooperate closely to achieve this goal, namely, the matrix adhesion and signaling receptors, the integrins, and matrix-degrading and -processing enzymes, the matrix metalloproteinases (MMPs). There is now substantial experimental evidence that blocking key molecules of either group will prevent or seriously delay wound-healing. It has been known for some time now that cell adhesion by means of the integrins regulates the expression of MMPs. In addition, certain MMPs can bind to integrins or other receptors on the cell surface involved in enzyme activation, thereby providing a mechanism for localized matrix degradation. By proteolytically modifying the existing matrix molecules, the MMPs can then induce changes in cell behavior and function from a state of rest to migration. During wound repair, the expression of integrins and MMPs is simultaneously up-regulated. This review will focus on those aspects of the extensive knowledge of fibroblast and keratinocyte MMPs and integrins in biological processes that relate to wound-healing.

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