Role of T cells in ischemic acute kidney injury and repair

Ischemic acute kidney injury (AKI) is a common medical problem with significant mortality and morbidity, affecting a large number of patients globally. Ischemic AKI is associated with intrarenal inflammation as well as systemic inflammation; thus, the innate and adaptive immune systems are implicated in the pathogenesis of ischemic AKI. Among various intrarenal immune cells, T cells play major roles in the injury process and in the repair mechanism affecting AKI to chronic kidney disease transition. Importantly, T cells also participate in distant organ crosstalk during AKI, which affects the overall outcomes. Therefore, targeting T cell-mediated pathways and T cell-based therapies have therapeutic promise for ischemic AKI. Here, we review the major populations of kidney T cells and their roles in ischemic AKI.

Perioperative risk factors of progressive chronic kidney disease following liver transplantation: analyses of a 10-year follow-up single-center cohort

Purpose@#The incidence of chronic kidney disease (CKD) has been increasing due to improved survival after liver transplantation (LT). Risk factors of kidney injury after LT, especially perioperative management factors, are potentially modifiable. We investigated the risk factors associated with progressive CKD for 10 years after LT. @*Methods@#This retrospective cohort study included 292 adult patients who underwent LT at a tertiary referral hospital between 2000 and 2008. Renal function was assessed by the e stimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula. The area under the curve of serial eGFR (AUCeGFR) was calculated for each patient to assess the trajectory of eGFR over the 10 years. Low AUCeGFR was considered progressive CKD. Linear regression analyses were performed to examine the associations between the variables and AUCeGFR. @*Results@#Multivariable analysis showed that older age (regression coefficient = -0.53, P < 0.001), diabetes mellitus (DM) (regression coefficient = -6.93, P = 0.007), preoperative proteinuria (regression coefficient = -16.11, P < 0.001), preoperative acute kidney injury (AKI) (regression coefficient = -14.35, P < 0.001), postoperative AKI (regression coefficient = -3.86, P = 0.007), and postoperative mean vasopressor score (regression coefficient = -0.45, P = 0.034) were independently associated with progressive CKD. @*Conclusion@#More careful renoprotective management is required in elderly LT patients with DM or preexisting proteinuria. Postoperative AKI and vasopressor dose may be potentially modifiable risk factors for progressive CKD.

Perioperative risk factors of progressive chronic kidney disease following liver transplantation: analyses of a 10-year follow-up single-center cohort

Purpose@#The incidence of chronic kidney disease (CKD) has been increasing due to improved survival after liver transplantation (LT). Risk factors of kidney injury after LT, especially perioperative management factors, are potentially modifiable. We investigated the risk factors associated with progressive CKD for 10 years after LT. @*Methods@#This retrospective cohort study included 292 adult patients who underwent LT at a tertiary referral hospital between 2000 and 2008. Renal function was assessed by the e stimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula. The area under the curve of serial eGFR (AUCeGFR) was calculated for each patient to assess the trajectory of eGFR over the 10 years. Low AUCeGFR was considered progressive CKD. Linear regression analyses were performed to examine the associations between the variables and AUCeGFR. @*Results@#Multivariable analysis showed that older age (regression coefficient = -0.53, P < 0.001), diabetes mellitus (DM) (regression coefficient = -6.93, P = 0.007), preoperative proteinuria (regression coefficient = -16.11, P < 0.001), preoperative acute kidney injury (AKI) (regression coefficient = -14.35, P < 0.001), postoperative AKI (regression coefficient = -3.86, P = 0.007), and postoperative mean vasopressor score (regression coefficient = -0.45, P = 0.034) were independently associated with progressive CKD. @*Conclusion@#More careful renoprotective management is required in elderly LT patients with DM or preexisting proteinuria. Postoperative AKI and vasopressor dose may be potentially modifiable risk factors for progressive CKD.

Chemical Regeneration of Wound Defects: Relevance to the Canine Palatal Mucosa and Cell Cycle Up-Regulation in Human Gingival Fibroblasts

BACKGROUND: Trichloroacetic acid (TCA) is an agent widely applied in dermatology for skin regeneration. To test whether TCA can offer an advantage for the regeneration of oral soft tissue defects, the cellular events following TCA application were explored in vitro and its influence on the oral soft tissue wound healing was evaluated in a canine palate model.METHODS: The cytotoxicity and growth factor gene expression in human gingival fibroblasts were tested in vitro following the application of TCA at four concentrations (0.005%, 0.05%, 0.5% and 1%) with different time intervals (0, 3, 9 and 21 h). One concentration of TCA was selected to screen the genes differentially expressed using DNA microarray and the associated pathways were explored. TCA was injected in open wound defects of the palatal mucosa from beagle dogs (n = 3) to monitor their healing and regeneration up to day 16-post-administration.RESULTS: While the 0.5–1% concentration induced the cytoxicity, a significantly higher expression of growth factor genes was observed after 3 and 9 h following the 0.5% TCA application in comparison to other groups. DNA microarray analysis in 0.5% TCA group showed 417 genes with a significant 1.5-fold differential expression, involving pathways of cell cycle, FoxO signaling, p53 signaling, ubiquitin mediated proteolysis and cAMP signaling. In vivo results showed a faster reepithelialization of TCA-treated wounds as compared to spontaneous healingCONCLUSION: TCA promoted the healing and regeneration of oral soft tissue wound defects by up-regulating the cell cycle progression, cell growth, and cell viability, particularly at a concentration of 0.5%.

Regulation of human gingival fibroblast gene expression on microgrooves: A DNA microarray study / 대한치과보철학회지

PURPOSE: We aimed to investigate the gene expression of human gingival fibroblasts on microgroove surface using DNA microarray. MATERIALS AND METHODS: Microgrooves were applied on grade II titanium discs to have 0/0 µm (NE0, control group), 60/10 µm (E60/10, experimental group) of respective width/depth by photolithography. The entire surface of the microgrooved Ti substrata was further acid etched and used as the two experimental groups in this study. Human gingival fibroblasts were cultured in the experimental group and the control group, and total RNA was extracted. The oligonucleotide microarray was performed to confirm the changes of various gene expression levels between experimental group and control group. Changes of gene expression level were determined at the pathway level by mapping the expression results of DNA chips, using the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis. RESULTS: Gene expression levels on E60/10 and NE0 were analyzed, there were 123 genes showing significant differences in expression more than 1.5 times on E60/10 microgrooved surface compared to NE0 surface, and 19 genes showing significant differences in expression more than 2 times. The KEGG pathway analysis confirmed the changes in gene expression levels under experimental conditions. Cell signaling, proliferation, and activity among the various gene expression results were identified. CONCLUSION: Microgrooved surfaces induce gene expression changes and related cell signaling. According to the results of this study, microgrooves can be used as the surface of various biomaterials which need to improve cell activity through gene expression changes and activation of cell signaling.

Endoscopic Findings of Enteropathy-Associated T-Cell Lymphoma Type II: A Case Series

Enteropathy-associated T-cell lymphoma (EATL) is a rare extranodal T-cell lymphoma arising from the intestine. Two types of EATL have been reported. In contrast to the classic EATL type I, EATL type II occurs sporadically, is unrelated to celiac disease, and comprises 10% to 20% of all EATL cases. A total of five cases of EATL type II were diagnosed at our clinic from January 2009 to September 2012. Four of the five patients were diagnosed with the help of endoscopy. Among the four patients, two of the cases involved both the small and large intestines, whereas in the other two patients, EATL was limited to the small intestine. Common endoscopic findings included innumerable fine granularities (also called mosaic mucosal patterns) and diffuse thickening of the mucosa with a semicircular shallow ulceration in the lesions of the small bowel. In contrast, the endoscopic findings of the colon were nonspecific and could not distinguish EATL type II from other diseases. There are only few published reports regarding the representative endoscopic findings of EATL. Here, we present the clinical and endoscopic findings of four cases of EATL type II diagnosed by endoscopy.

Delayed Perforation Occurring after Endoscopic Submucosal Dissection for Early Gastric Cancer

Delayed perforation is a very rare complication of endoscopic submucosal dissection (ESD), with a reported incidence of 0.1% to 0.45%. Few reports exist on the clinical features and outcomes of delayed perforation after ESD, and it is unclear whether the optimal management strategy is emergency surgery or endoscopic closure with conservative treatment. Here, we report two cases of delayed perforation occurring after ESD for early gastric cancer. In both cases, lesions were located in the antrum, and tumor depths were confined to the mucosal layer. Total procedure times for ESD were 25 and 45 minutes, respectively. Because delayed perforation may be associated with excessive thermal damage and necrosis of the muscle layer, treatment with emergency surgery should be used instead of conservative management in cases of delayed perforation after ESD.

Aggravation of Hepatopulmonary Syndrome after Sildenafil Treatment in a Patient with Coexisting Portopulmonary Hypertension

Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPHTN) are complications of portal hypertension and cirrhosis. Their pathophysiological mechanisms clearly differ. HPS is characterized by a defect in arterial oxygenation induced by pulmonary vascular dilatation. In contrast, PPHTN is predominantly due to excessive pulmonary vasoconstriction and vascular remodeling, but is rarely associated with hypoxia. We report a case of a patient who had both HPS and PPHTN at the time of presentation. HPS was aggravated after sildenafil administration for the treatment of PPHTN. We demonstrated increased amount of intrapulmonay shunt after sildenafil challenge by using agitated saline contrast transthoracic echocardiography.