Hyperkalemia in a patient with myasthenia gravis: case presentation.

BACKGROUND: Myasthenia gravis (MG) is the most common disorder of neuromuscular transmission, and it is typified by fluctuating degrees and variable combinations of weakness in the ocular, bulbar, limb, and respiratory muscles. Under rare circumstances, MG can be accompanied by Addison's disease. CASE PRESENTATION: Here, we reported the case of a 57-year-old Chinese woman with MG. She experienced progressive muscle weakness for 1 week. MG with acute exacerbation was initially suspected. However, further biochemistry tests found mild hyperkalemia (5.6 mEq/L) and a lower renal potassium excretion rate. Consequently, low aldosterone action was highly suspected. Further findings included a suppressed cortisol level, a higher adrenocorticotropic hormone concentration, and 21-hydroxylase antibody positivity, supporting a diagnosis of primary adrenal insufficiency due to autoimmune adrenalitis. CONCLUSION: We successfully demonstrated that adrenal insufficiency could be diagnosed, due to the presence of hyperkalemia. This case suggested a need for clinicians to consider the possible coincidence of adrenal insufficiency in a patient with MG and hyperkalemia. Early hormone supplementation should be begun.

Higher Intra-Dialysis Serum Phosphorus Reduction Ratio as a Predictor of Mortality in Patients on Long-Term Hemodialysis.

BACKGROUND Rapid shifting between extracellular and intracellular phosphorus can occur during dialysis sessions, which can cause aberrant intracellular signaling in long-term hemodialysis (LTHD) patients. However, the effect of these intra-dialysis fluctuations of phosphorus on clinical outcomes has not been examined. Therefore, we investigated the relationship between intradialysis serum phosphorus reduction ratio (IDSPRR) and mortality in LTHD patients. MATERIAL AND METHODS This was a retrospective, observational cohort study to assess the predictive power of IDSPRR (>0.63 vs. ≤0.63) on mortality in a total of 805 LTHD patients. All these fatal events were analyzed using the Cox proportional hazards regression model. RESULTS After multivariable analysis, baseline IDSPRR higher than 0.63 was significantly predictive of all-cause mortality (hazard ratio [HR]: 1.58; 95% confidence interval [CI]: 1.10-2.26), but not for cardiovascular (CV) mortality (HR: 1.41; 95% CI: 0.91-2.18). However, when time-varied IDSPRRs were applied, a value greater than 0.63 was not only significantly predictive of all-cause mortality (HR: 1.74, 95% CI: 1.16-2.63), but also CV mortality (HR: 2.04, 95% CI: 1.23-3.40). CONCLUSIONS High IDSPRR (>0.63) is independently associated with increased all-cause and CV mortality, which shows the negative effect of rapid intracellular phosphorus-shifting on LTHD patients.

An atypical presentation of high potassium renal secretion rate in a patient with thyrotoxic periodic paralysis: a case report.

BACKGROUND: Hypokalemia is one of the most common clinical electrolyte imbalance problems, and thyrotoxic periodic paralysis (TPP) is a leading cause of presentation to the emergency department. Low renal potassium secretion rates, a normal acid-base balance in the blood, and hyperthyroidism are the hallmarks of suspected TPP. CASE PRESENTATION: Here we report the case of a 36-year-old man who presented to the emergency department with a sudden onset of acute muscle weakness at 5 h prior to admission. Biochemistry tests revealed hypokalemia with hyperthyroidism and renal potassium wasting. TPP was initially not favored due to the presence of renal potassium wasting. However, his serum potassium level rebounded rapidly within several hours after potassium supplementation, indicating that the intracellular shifting of potassium ions was the main etiology for his hypokalemia. The early stage of TPP development may have contributed to this paradox. CONCLUSION: Therefore, it is premature to rule out TPP based on the presentation of high renal potassium secretion rates alone. This finding may result in an incorrect impression being made in the early stage of TTP and may consequently lead to an inappropriate potassium supplementation policy.

Endothelial Progenitor Cells Predict Long-Term Mortality in Hemodialysis Patients.

BACKGROUND: The endothelial progenitor cells (EPCs) dysfunction is a critical event in the initiation of atherosclerotic plaque development and the level of circulating EPCs can be considered a biomarker of cardiovascular events. The level and functional change in EPCs has been investigated in hemodialysis patients, but the effect of absolute number of EPCs on risk of death has not yet been explored. We hypothesized that the number of EPCs predicted death from cardiovascular and all-cause mortality in hemodialysis patients. METHODS: We evaluate the association between endothelial progenitor cells and clinical outcome in 154 patients on maintenance hemodialysis. The blood sample was drawn at the time of patient enrollment and EPCs were identified by flow cytometry using triple staining for CD34/CD133/KDR. RESULTS: The median duration of follow-up was 4.19 years. There were 79 (51.3%) deaths during the follow-up period, 41 of whom died due to a confirmed cardiovascular cause. The cumulative survival was greater in the high-EPC group than the low-EPC group for all-cause and cardiovascular mortality. Decreased EPCs levels were associated with a significant increase in the risk of cardiovascular and all-cause mortality after adjusting for age, gender, current smokers, diabetes mellitus, and hypertension. CONCLUSIONS: The level of circulating EPCs independently predicts the clinical outcome in patients on maintenance hemodialysis. Thus, the EPCs levels may be a useful predictive tool for evaluating the risk of death in maintenance hemodialysis patients.

Simultaneous occurrence of fibrillary glomerulonephritis and renal lesions in nonmalignant monoclonal IgM gammopathy.

BACKGROUND: Fibrillary glomerulonephritis (FGN) is a rare primary glomerular disease that seldom coexists with other diseases. Membranoproliferative glomerulonephritis is a pathologic finding of renal lesions associated with IgM-secreting monoclonal proliferations. We present a case study of a patient with unusual simultaneous FGN and IgM-related renal disorder in nonmalignant monoclonal IgM gammopathy. CASE PRESENTATION: A 63-year-old male presented with nephrotic syndrome and elevated serum creatinine levels. Laboratory examination revealed elevated levels of serum IgM and low C3 levels. Serum and urine immunofixation electrophoresis showed a monoclonal IgM with a kappa light chain. A bone marrow biopsy revealed less than 5 % bone marrow infiltration by lymphoplasmacytic lymphoma, and a renal biopsy revealed mesangiocapillary glomerulonephritis on light microscopy. Immunofluorescent and immunohistochemical staining indicated granular deposits of immunoglobulin G in the mesangium and granular deposits of immunoglobulin M and κ light chains along the capillary wall. Electron microscopy revealed randomly arranged nonbranching fibrils of approximately 15 nm in diameter in the glomerular mesangium and subendothelial electron-dense deposits. According to these results, we confirmed FGN and membranoproliferative glomerulonephritis, which were attributed to monoclonal IgM deposits. CONCLUSION: To the best of our knowledge, this is the first report of simultaneous FGN and membranoproliferative glomerulonephritis in nonmalignant IgM monoclonal gammopathy.

Association of interleg difference of ankle brachial index with overall and cardiovascular mortality in chronic hemodialysis patients.

BACKGROUND: The ankle-brachial index (ABI) is associated with peripheral vascular atherosclerosis, adverse cardiovascular outcomes, and all-cause mortality. However, there were limited data available on studying the effect of interleg ABI difference. METHODS: We investigated the association of the interleg ABI difference with overall and cardiovascular mortality in chronic hemodialysis in a retrospective observational cohort of 369 Taiwanese patients undergoing chronic hemodialysis. RESULTS: An interleg ABI difference of ≥0.15 in hemodialysis patients had significant predictive power for all-cause and cardiovascular mortality in crude analysis. The hazard ratio (HR) for all-cause mortality was 3.00 [95% confidence interval (CI), 1.91-4.71]; the HR for cardiovascular mortality was 3.13 (95% CI, 1.82-5.38). After adjustment for confounding variables, this difference continued to have significant predictive power for all-cause mortality but lost its predictive power for fatal cardiac outcome. ABI <0.9 and high brachial-ankle pulse wave velocity were independently associated with an interleg ABI difference of ≥0.15 in hemodialysis patients. Moreover, in the subgroup analysis, we found that this difference was an independent factor for overall and cardiovascular mortality, particularly in elder patients, female patients, or those with ABI <0.9. CONCLUSION: Detection of an interleg ABI difference of ≥0.15 was an independent risk factor for overall mortality in hemodialysis patients but it may affect cardiovascular mortality through the effect of peripheral vascular disease.

The immediate and one-year outcomes of dialysis patients with refractory angina treated by enhanced external counterpulsation.

Adult dialysis patients with angina pectoris refractory to medical treatment or revascularization are not uncommon. Enhanced external counterpulsation (EECP) has been proven to be effective in reducing myocardial ischemia and refractory angina. The objective of this study was to assess the immediate and 1-year effects of EECP treatment in dialysis patients with refractory angina. Thirty-six consecutive dialysis patients were treated with EECP, and a follow-up was conducted after 1 year. The Canadian Cardiovascular Society (CCS) Angina Grading Scale was used to measure angina severity. Medications were recorded before EECP treatment, at the end of treatment, and at 1-year follow-up. Adverse events and risk factors of cardiovascular disease were recorded and analyzed. At 1-year follow-up, data from patients improving by at least one CCS class after treatment were compared with data from patients showing no improvement. The improvement rates in CCS class were 85% immediately after EECP and 66% at 1-year follow-up. Thallium-201 myocardial perfusion imaging demonstrated a reversible resolution of 40% and improvement of 25% immediately after EECP treatment. Diabetes mellitus and high serum phosphate levels were risk factors affecting whether the beneficial effects of EECP treatment could be sustained (p < 0.05). Major adverse events were rare. EECP shows potential for refractory angina in dialysis patients. The beneficial effects were sustained for more than 1 year in 66% patients. Diabetes mellitus and high serum phosphate levels were major factors impacting the sustained effectiveness of EECP treatment. Nonetheless, adequately powered future studies are necessary to assess safety and efficacy of this procedure.

Tinzaparin provides lower lipid profiles in maintenance hemodialysis patients: a cross-sectional observational study.

As a low-molecular-weight heparin, tinzaparin has effectively been used as an anticoagulant during hemodialysis sessions. However, the impact of different heparin types on dyslipidemia is still controversial. In our study, 434 chronic hemodialysis patients were evaluated. The mean age was 65 ± 13. Forty-eight patients (11%) and 386 patients (89%) were in the tinzaparin and unfractionated heparin (UFH) groups, respectively. Triglyceride had significant difference between the two groups (P = 0.001) but total cholesterol, HDL, or LDL did not. In the univariate analysis, the triglyceride level was significantly associated with tinzaparin use [ß: -39.9, 95% confidence interval (CI): -76.7 to -3.0], and this association remained following the multivariate analysis (ß: -40.8, 95% CI: -75.1 to -6.5). The difference in serum total cholesterol level between tinzaparin and UFH became significant (ß: -13, 95% CI: -24.5 to -1.56) after adjustment in the multivariate analysis. Moreover, in a subgroup analysis, male diabetic patients showed lower serum triglyceride levels with the use of tinzaparin, while older, nondiabetic, male patients showed significant advantages in total cholesterol levels with the use of tinzaparin. Based on our findings, tinzaparin shows a significant association with a lower lipid profile in patients with chronic hemodialysis when compared to UFH.

Epigallocatechin-3-gallate combined with alpha lipoic acid attenuates high glucose-induced receptor for advanced glycation end products (RAGE) expression in human embryonic kidney cells.

The anti-oxidant effects of epigallocatechin gallate (EGCG) and alpha lipoic acid (ALA) have been demonstrated in previous studies. The kidney protection effects of EGCG and ALA in patients with kidney injury are still under investigation. The purpose of this study is to investigate the anti-inflammatory and anti-oxidant effects of EGCG and ALA on high glucose-induced human kidney cell damage. EGCG inhibited high glucose(HG)-induced TNF-α and IL-6 production in human embryonic kidney (HEK) cells. Both EGCG and ALA decreased HG-induced receptor of advanced glycation end products (RAGE) mRNA and protein expressions in HEK cells. EGCG and ALA also recovered HG-inhibited superoxide dismutase production and decreased ROS expressions in HEK cells. The synergism of EGCG and ALA was also studied. The effect of EGCG combined with ALA is greater than the effect of EGCG alone in all anti-inflammation and anti-oxidant experiments. Our studies provide a potential therapeutic application of EGCG and ALA in preventing progression of diabetic nephropathy.

Image Quality of 256-Slice Computed Tomography for Coronary Angiography.

PURPOSE: To assess the image quality of 256-slice computed tomographic angiography (CTA) and to identify possible impact factors associated with image quality. METHODS: From November 2009 to January 2010, 506 patients underwent 256-slice CTA at our institute. A total of 451 patients were enrolled in our study, after 55 patients were excluded because of prior bypass surgery and stenting. CTA image quality was graded by two observers using a 4-point scale: excellent (score 1), good (score 2), moderate (score 3), poor and non-diagnostic (score 4). The coronary arteries were divided into 15 segments. Image quality was correlated to the subjects' age, gender, body mass index, heart rate, and calcium scores. RESULTS: We evaluated 6650 coronary segments from CTA images of our enrolled 451 patients. The mean image quality score of all coronary segments was 1.14. Most coronary segments (99.7%) were assessable, and only 21 segments (0.3%) were non-diagnostic. A total of 5824 coronary segments were classified as having excellent image quality. Forty-two patients (9.3%) required control of heart rate with beta-blockers before CTA could be performed. Male patients had better image quality than female patients. Heart rate and severity of calcification were impact factors associated with image quality. CONCLUSIONS: Examination with 256-slice CTA provides good image quality and can effectively evaluate most coronary segments. KEY WORDS: Coronary angiography; Heart rate; Image quality; Multi-slice computed tomography.

Glucagon-like peptide-1 receptor regulates receptor of advanced glycation end products in high glucose-treated rat mesangial cells.

BACKGROUND: Hyperglycemia-induced advanced glycation end products (AGEs) and receptor for AGEs (RAGEs) play major roles in diabetic nephropathy progression. In previous study, both glucagon-like peptide-1 (GLP-1) and peroxisome proliferator-activated receptors delta (PPARδ) agonists were shown to have anti-inflammatory effect on AGE-treated rat mesangial cells (RMCs). The interaction among PPARδ agonists, GLP-1, and AGE-RAGE axis is, however, still unclear. METHODS: In this study, the individual and synergic effect of PPARδ agonist (L-165 041) and siRNA of GLP-1 receptor (GLP-1R) on the expression of GLP-1, GLP-1R, RAGE, and cell viability in AGE-treated RMCs were investigated. RESULTS: L-165 041 enhanced GLP-1R mRNA and protein expression only in the presence of AGE. The expression of RAGE mRNA and protein was enhanced by AGE, attenuated by L-165 041, and siRNA of GLP-1R reversed L-165 041-induced inhibition. Cell viability was also inhibited by AGE. L-165 041 attenuated AGE-induced inhibition and siRNA GLP-1R diminished L-165 041 effect. CONCLUSION: PPARδ agonists increase GLP-1R expression on RMC in the presence of AGE. PPARδ agonists also attenuate AGE-induced upregulated RAGE expression and downregulated cell viability. The effect of PPARδ agonists needs the cooperation of GLP-1R activation.

The effects of gold nanoparticles in wound healing with antioxidant epigallocatechin gallate and α-lipoic acid.

Topical applications of antioxidant agents in cutaneous wounds have attracted much attention. Gold nanoparticles (AuNPs), epigallocatechin gallate (EGCG), and α-lipoic acid (ALA) were shown to have antioxidative effects and could be helpful in wound healing. Their effects in Hs68 and HaCaT cell proliferation and in mouse cutaneous wound healing were studied. Both the mixture of EGCG + ALA (EA) and AuNPs + EGCG + ALA (AuEA) significantly increased Hs68 and HaCaT proliferation and migration. Topical AuEA application accelerated wound healing on mouse skin. Immunoblotting of wound tissue showed significant increase of vascular endothelial cell growth factor and angiopoietin-1 protein expression, but no change of angiopoietin-2 or CD31 after 7 days. After AuEA treatment, CD68 protein expression decreased and Cu/Zn superoxide dismutase increased significantly in the wound area. In conclusion, AuEA significantly accelerated mouse cutaneous wound healing through anti-inflammatory and antioxidation effects. This study may support future studies using other antioxidant agents in the treatment of cutaneous wounds. FROM THE CLINICAL EDITOR: In this study, topically applied gold nanoparticles with epigallocatechin gallate and alpha-lipoic acid were studied regarding their effects in wound healing in cell cultures. Significant acceleration was demonstrated in wound healing in a murine model.

Factors affecting arteriovenous access patency after percutaneous transluminal angioplasty in chronic haemodialysis patients under vascular access monitoring and surveillance: a single-centre observational study.

OBJECTIVES: Maintenance of vascular access (VA) patency after percutaneous transluminal angioplasty (PTA) is important and remains a challenge despite VA monitoring and surveillance. The aim of this study was to examine factors affecting the post-PTA arteriovenous access (AVA) patency in patients who have been on close VA monitoring and surveillance for access flow. DESIGN: Retrospective cohort study. SETTING: A single medical centre in Taiwan. PARTICIPANTS: Records of patients who received chronic haemodialysis between 1 January 2017 and 31 December 2018 were retrospectively reviewed. Patients were divided into two groups (without or with PTA intervention on AVA). PRIMARY AND SECONDARY OUTCOME: Patients were followed until reintervention PTA, termination or abandoned VA or end of study. In addition to routine monitoring, VA flow surveillance was performed every 3 months for detection of VA dysfunction adhering to Kidney Disease Outcomes Quality Initiative guidelines. RESULTS: A total of 508 patients were selected for study inclusion (with PTA, n=231; without PTA, n=277). At baseline, variables that differed between groups included malignancy and levels of albumin, uric acid, potassium, phosphorous, high-density lipoprotein, total bilirubin and ferritin (all p<0.05). Significant between-group differences were observed for ß-adrenergic blocking agents (with PTA, 49.8%; without PTA, 37.5%; p, 0.007) and ADP inhibitors (with PTA, 23.8%; without PTA, 11.2%; p<0.001). Among patients with PTA, those with acute myocardial infarction, high ferritin level or arteriovenous graft (AVG) had a significantly higher risk of reintervention post-PTA (p<0.05). Dipeptidyl peptidase-4 inhibitors, thiazolidinediones, ADP inhibitors, and warfarin use were predictors of post-PTA patency (p<0.05). CONCLUSIONS: AVG access type, acute myocardial infarction, and high ferritin levels are risk factors for re-intervention post-PTA. These findings may be useful in the development of prophylactic strategies for monitoring VA function and tailoring surveillance programs for these dialysis patients.

Serotonin receptor subtype-2B signaling is associated with interleukin-18-induced cardiomyoblast hypertrophy in vitro.

Background: In patients with heart failure, interleukin-18 (IL-18) levels increase in the circulatory system and injured myocardial tissue. Serotonin (5-hydroxytryptamine) receptors subtype 2B (HTR2B) play an essential role in cardiac function and development, and their overexpression in rats leads to myocardial hypertrophy. Epigallocatechin gallate (EGCG) is cardioprotective in myocardial ischemia-reperfusion injury in rats and can prevent pressure overload-mediated cardiac hypertrophy in vivo. Mice deficient in peroxisome proliferator-activated receptor delta (PPARδ) can have cardiac dysfunction, myocardial hypertrophy, and heart failure. Matrix metalloproteinases (MMPs) are possibly involved in cardiac remodeling. However, the relationship between IL-18 signaling, cardiac hypertrophy, and the molecular mechanisms involved remain to be fully elucidated. Objectives: To elucidate the relationship between HTR2B and IL-18-induced myocardial hypertrophy and examine the antihypertrophic effects of EGCG and PPARδ. Methods: We induced H9c2 cardiomyoblast hypertrophy with IL-18 in vitro and investigated the downstream signaling by real-time polymerase chain reaction (PCR) and western blotting. Hypertrophy was assessed by flow cytometry. We determined the effects of EGCG and PPARδ on IL-18-induced hypertrophic signaling via HTR2B-dependent mechanisms. Results: IL-18-induced H9c2 hypertrophy upregulated brain natriuretic peptide (BNP) protein and mRNA expression by inducing the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and the hypertrophy was attenuated by pretreatment with EGCG (20 µM) and L-165,041 (2 µM), a PPARδ agonist. IL-18 upregulated the expression of HTR2B, which was inhibited by pretreatment with EGCG and L-165,041. SB215505 (0.1 µM), a HTR2B antagonist and siRNA for HTR2B, attenuated H9c2 hypertrophy significantly. Inhibition of HTR2B also downregulated the expression of MMP-3 and MMP-9. Conclusions: IL-18 and HTR2B play critical roles in cardiomyoblast hypertrophy. EGCG and L-165,041 inhibit the expression of HTR2B and augment remodeling of H9c2 cardiomyoblasts, possibly mediated by MMP-3 and MMP-9.

Topical Application of Antrodia cinnamomea Ointment in Diabetic Wound Healing.

The number of diagnosed diabetic patients is increasing worldwide. Many people with diabetes develop wounds that are slow to, or never, heal, which can lead to serious health issues. Diabetes causes long-term excessive blood glucose buildup in human body, which leads to an over-reactive inflammatory response and excessive oxidative stress. As a result, varied wound healing effects were observed according to different circumstances and stage of healing. We used two diabetic wound animal models to analyze the wound healing effect of Antrodia cinnamomea ointment in either topical application and/or oral administration, and explored its mechanism by Western blot analysis. The results showed that topical Antrodia cinnamomea treatment can significantly promote wound healing. The increased expressions of angiopoietin 1 and angiopoietin 2 protein and reduction of CD68 expression were found around wound area. Simultaneous treatment of oral and topical Antrodia cinnamomea ointment did not show an accelerated healing effect in our animal model. This study is the first report to demonstrate the effect of topical application of Antrodia cinnamomea ointment on diabetic wounds healing, and its relationship with angiogenesis. This may also open a new field for future development and application of Taiwan Antrodia cinnamomea.

Long-term safety and efficacy of ferric citrate in phosphate-lowering and iron-repletion effects among patients with on hemodialysis: A multicenter, open-label, Phase IV trial.

BACKGROUND: We explored the long-term safety and efficacy of ferric citrate in hemodialysis patients in Taiwan, and further evaluated the iron repletion effect and change of iron parameters by different baseline groups. METHODS: This was a 12-month, Phase IV, multicenter, open-label study. The initial dose of ferric citrate was administered by patients' clinical condition and further adjusted to maintain serum phosphorus at 3.5-5.5 mg/dL. The primary endpoint was to assess the safety profiles of ferric citrate. The secondary endpoints were to evaluate the efficacy by the time-course changes and the number of subjects who achieved the target range of serum phosphorus. RESULTS: A total of 202 patients were enrolled. No apparent or unexpected safety concerns were observed. The most common treatment-emergent adverse events were gastrointestinal-related with discolored feces (41.6%). Serum phosphorus was well controlled, with a mean dose of 3.35±1.49 g/day, ranging from 1.5 to 6.0 g/day. Iron parameters were significantly improved. The change from baseline of ferritin and TSAT were 227.17 ng/mL and 7.53%, respectively (p-trend<0.001), and the increase started to slow down after 3-6 months of treatment. In addition, the increase trend was found only in patients with lower baseline level of ferritin (≤500 ng/mL) and TSAT (<30%). CONCLUSIONS: Ferric citrate is an effective phosphate binder with favorable safety profile in ESRD patients. The iron-repletion by ferric citrate is effective, and the increase is limited in patients with a higher baseline. In addition to controlling hyperphosphatemia, ferric citrate also shows additional benefits in the treatment of renal anemia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03256838; 12/04/2017.

Hydralazine attenuates renal inflammation in diabetic rats with ischemia/reperfusion acute kidney injury.

Acute kidney injury (AKI) is one of the major complications with increased oxidative stress and inflammation in diabetic patients. Hyperglycemia stimulates the formation of advanced glycation end products (AGEs). However, hyperglycemia directly triggers the interaction between AGEs and transmembrane AGEs receptors (RAGE), which enhances oxidative stress and increases the production of inflammatory substances. Therefore, diabetes plays a pivotal role in kidney injury. Hydralazine, a vasodilator and antihypertensive drug, was found to have the ability to reduce ROS, oxidative stress, and inflammation. We applied Hydralazine co-culture with AGEs in rat mesangial cells (RMC) and to renal ischemia/reperfusion(I/R) injury models in streptozotocin-induced diabetic rats. Hydralazine significantly decreased AGEs-induced RAGE, iNOS, and COX-2 expressions in RMC. Compared to the diabetic with AKI group, hydralazine decreased inflammation-related protein, and JAK2, STAT3 signaling in rat kidney tissue. Our studies indicate that Hydralazine has the potential to become a beneficial drug in the treatment of diabetic acute kidney injury.

The Cell Protective Effect of Adenine on Hypoxia-Reoxygenation Injury through PPAR Delta Activation.

Ischemia followed by blood supply reperfusion in cardiomyocytes leads to an overproduction of free radicals and a rapid decrease of adenosine triphosphate concentration. The cardioprotective effect of a potential drug, adenine, was evaluated using H9c2 rat cardiomyoblasts. After hypoxia-reoxygenation (HR) treatment consisting of hypoxia for 21 h followed by reoxygenation for 6 h, it was revealed that pretreatment with 200 µM adenine for 2 h effectively prevented HR-induced cell death. Adenine also significantly decreased the production of reactive oxygen species and reduced cell apoptosis after HR injury. The antioxidant effect of adenine was also revealed in this study. Adenine pretreatment significantly reduced the expression of activating transcription factor 4 (ATF4) and glucose-regulated protein 78 (GRP78) proteins, and protein disulfide isomerase induced a protective effect on mitochondria after HR stimulation. Intracellular adenosine monophosphate-activated protein kinase, peroxisome proliferator-activated receptor delta (PPARδ), and perilipin levels were increased by adenine after HR stimulation. Adenine had a protective effect in HR-damaged H9c2 cells. It may be used in multiple preventive medicines in the future.

Advanced glycation end products-induced apoptosis attenuated by PPARdelta activation and epigallocatechin gallate through NF-kappaB pathway in human embryonic kidney cells and human mesangial cells.

BACKGROUND: Diabetic nephropathy has attracted many researchers' attention. Because of the emerging evidence about the effects of advanced glycation end products (AGEs) and receptor of AGE (RAGE) on the progression of diabetic nephropathy, a number of different therapies to inhibit AGE or RAGE are under investigation. The purpose of the present study was to examine whether peroxisome proliferator-activated receptor delta (PPARdelta) agonist (L-165041) or epigallocatechin gallate (EGCG) alters AGE-induced pro-inflammatory gene expression and apoptosis in human embryonic kidney cells (HEK293) and human mesangial cells (HMCs). METHODS: The HEK cells and HMC were separated into the following groups: 100 microg/mL AGE alone for 18 h; AGE treated with 1 microM L-165041 or 10 microM EGCG, and untreated cells. Inflammatory cytokines, nuclear factor-kappaB pathway, RAGE expression, superoxide dismutase and cell apoptosis were determined. RESULTS: AGE significantly increased tumour necrosis factor-alpha (TNF-alpha), a major pro-inflammatory cytokine. The mRNA and protein expression of RAGE were up-regulated. These effects were significantly attenuated by pre-treatment with L-165041 or EGCG. AGE-induced nuclear factor-kappaB pathway activation and both cells apoptosis were also inhibited by L-165041 or EGCG. Furthermore, both L-165041 and EGCG increased superoxide dismutase levels in AGE-treated HEK cells and HMC. CONCLUSIONS: This study demonstrated that PPARdelta agonist and EGCG decreased the AGE-induced kidney cell inflammation and apoptosis. This study provides important insights into the molecular mechanisms of EGCG and PPARdelta agonist in attenuation of kidney cell inflammation and may serve as a therapeutic modality to treat patients with diabetic nephropathy.