Jyh-Gang Leu

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

UNLABELLED 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.

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.

L-165,041, troglitazone and their combination treatment to attenuate high glucose-induced receptor for advanced glycation end products (RAGE) expression.

Diabetic nephropathy is the leading cause of end-stage renal disease in the most developed countries of the world. Hyperglycemia-induced advanced glycation end products (AGEs) and receptor for AGEs (RAGE) production, pro-inflammatory cytokine secretion, and oxidative stress activation play major roles in kidney cell injury and apoptosis. Peroxisome proliferator-activated receptor-gamma (PPARγ) agonists are used clinically as insulin sensitizers. This study evaluated the renoprotective effect of PPARγ (troglitazone) and PPARδ (L-165,041) agonists on human embryonic kidney 293 (HEK) and mesangial cells. Troglitazone (10 μM) and L-165,041 (1 μM) significantly inhibited high glucose (25mM)-induced interleukin-6 and TNF-α production, RAGE expression and NF-κB translocation in HEK cells. Furthermore, Troglitazone (10 μM) and L-165,041(1 μM) significantly increased SOD expression and attenuated apoptosis in HEK and mesangial cells. The inhibitory effect between 1 μM L-165,041 and 10 μM troglitazone showed no difference. Furthermore L-165,041 and troglitazone together did not increase the effects. These results provide important information for future application of PPAR agonists in diabetic nephropathy treatment.

Hypokalemic Paralysis Complicated by Concurrent Hyperthyroidism and Hyperaldosternoism: A Case Report

Patient: Female, 38 Final Diagnosis: Primary hyperaldosteronism Symptoms: Paralysis Medication: — Clinical Procedure: — Specialty: Nephrology Objective: Challenging differential diagnosis Background: Thyrotoxic periodic paralysis (TPP) is commonly observed in patients with acute paralysis and hyperthyroidism. However, there is a possibility of secondary causes of hypokalemia in such a setting. Case Report: Herein, we present the case of a 38-year-old woman with untreated hypertension and hyperthyroidism. She presented with muscle weakness, nausea, vomiting, and diarrhea since one week. The initial diagnosis was TPP. However, biochemistry tests showed hypokalemia with metabolic alkalosis and renal potassium wasting. Moreover, a suppressed plasma renin level and a high plasma aldosterone level were noted, which was suggestive of primary aldosteronism. Abdominal computed tomography confirmed this diagnosis. Conclusions: Therefore, it is imperative to consider other causes of hypokalemia (apart from TPP) in a patient with hyper-thyroidism but with renal potassium wasting and metabolic alkalosis. This can help avoid delay in diagnosis of the underlying disease.

Adenine accelerated the diabetic wound healing by PPAR delta and angiogenic regulation

Abstract Wound healing is one of the major complications of diabetes, and problems with wound healing in diabetics often lead to amputation and even death. AMP‐activated protein kinase (AMPK) is a protein involved in intracellular metabolism. Activated AMPK can reduce visceral fat and cholesterol synthesis and even inhibit hepatic gluconeogenesis. Activation of AMPK has been widely used in the treatment of type II diabetes. We applied an AMPK activator (Adenine) to human fibroblasts and to the wounds of streptozotocin‐induced diabetic mice. We applied Adenine ointment to the wounds on 7 consecutive days and observed the healing status as well as activation of AMPK and angiogenic factors. Based on the appearance of the wounds, the results showed that after 7 days of treatment the wound area was smaller in the Adenine‐treated group relative to the control group. The results for tissue protein expression showed that, compared to the control group, angiogenic related protein, PPAR&dgr; were increased and receptor for advanced glycation endproducts (RAGE) was decreased in the Adenine‐treated group. Our studies indicate that Adenine has the potential to become a useful drug in the treatment of diabetic wound healing.

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.

Association of vascular access flow with short-term and long-term mortality in chronic haemodialysis patients: a retrospective cohort study

Objectives To investigate the impact of vascular access flow (Qa) on vascular and all-cause mortality in chronic haemodialysis (HD) patients. Design Observational cohort study. Setting Single centre. Participants Adult chronic HD patients at the HD unit of Shin Kong Wu Ho-Su Memorial Hospital between 1 January 2003 and 31 December 2003 were recruited. Patients were excluded if they had arteriovenous fistula or arteriovenous graft failure within 3 months before the date of Qa measurement, were aged <18 years and had Qa levels of ≥2000mL/min. A total of 378 adult chronic HD patients were eventually enrolled for the study. Interventions The selected patients were evaluated with Qa and cardiac index (CI). They were divided into four groups according to three Qa cut-off points (500, 1000 and 1500 mL/min). Primary and secondary outcome measures Short-term and long-term vascular (cardiovascular or cerebrovascular) and all-cause mortality. Results Qa was positively correlated with CI (r=0.48, p<0.001). A Qa level of <1000 mL/min was independently associated with 1-year all-cause mortality (adjusted OR, 6.04; 95% CI 1.64 to 22.16; p=0.007). Kaplan-Meier analysis revealed that the cumulative incidence rates of all-cause and vascular mortality were significantly higher in the patients with a Qa level of <1000 mL/min (log-rank test; all p<0.01). Furthermore, a Qa level of <1000 mL/min was independently associated with long-term all-cause mortality (adjusted HR, 1.62; 95% CI 1.11 to 2.37; p=0.013); however, the risk of vascular mortality did not significantly increase after adjustment for confounders. Conclusions Qa is moderately correlated with cardiac function, and a Qa level of <1000 mL/min is an independent risk factor for both short-term and long-term all-cause mortality in chronic HD patients.

Peroxisome Proliferator-Activated Receptor Delta Agonists and AMP-Activated Protein Kinase Activators Reverse Interleukin 6-Inhibited Erythropoietin Receptor Expression

BACKGROUND: Interleukin-6 (IL-6) was shown to inhibit erythropoietin receptor (EpoR) expression in erythroid progenitor cells. The anti-inflammatory effects of peroxisome proliferator-activated receptor (PPAR) agonists and AMP-activated protein kinase (AMPK) activators have been proven in previous studies. This study is going to evaluate the effects of PPAR agonists and AMPK activators on IL-6- induced inhibition of EpoR expression and possible mechanisms. METHODS: Human erythroleukemia cells (K562) were incubated with IL-6 (5 ng/mL) for 18 hours in the presence and then absence of an AMPK activator HybriMore (200 μM) and peroxisome proliferatoractivated receptor δ (PPARδ) agonists L-165,041 (1 μM). The expression of EpoR and two downstream substances of AMPK, phosphorylated acetyl-CoA carboxylase (ACC), and glycogen synthase kinase (GSK) in K562 cells was measured. RESULTS: IL-6 significantly inhibited EpoR expression in K562 cells. HybriMore (200 μM) and L-165,041 (1 μM) significantly reversed IL-6 induced inhibition of EpoR expression with similar potency. IL-6 also significantly inhibited phosphorylated glycogen synthase kinase 3 (GSK3) and ACC expression. HybriMore showed no effect on IL-6-induced inhibition of phosphorylated GSK3 and ACC. L-165,041, however, reversed the inhibition of ACC, but had no effect on GSK3. CONCLUSION: Both PPAR agonists and AMPK activators significantly reverse IL-6-inhibited EpoR expression in K562 cells. The effect of AMPK activators may have no relationship with ACC or GSK3.

Corrosion‐like oesophagitis in a patient with polycystic kidneys and uraemia

Bromide-containing analgesic was discontinued from that day. Several weeks after discontinuation of bromidecontaining analgesic, she became quite well and her serum chloride level returned to the normal range. Severe forms of bromide intoxication are related to acute and chronic neurological symptoms: loss of consciousness, forgetfulness, ataxia, depression, mania, and hallucination etc. Fortunately, our patient did not develop neurological symptoms. Saline infusion is a standard treatment because bromide is cleared by the kidneys. The diagnosis should be confirmed by measuring serum bromide level. However, not all medical facilities routinely measure serum bromide concentration, and it usually takes several days to get the results from outsourcing companies. In this regard, it is important to diagnose tentatively by judging from serum chloride value and medical history, and treat patients depending on their clinical symptoms and discontinue the suspected drug immediately.

Proinflammatory Cytokines Inhibit Expression of Erythropoietin Receptor Messenger Ribonucleic Acid

BACKGROUND: Higher serum cytokine levels were shown to be accompanied with anemia in patients with chronic inflammatory diseases. The influence of proinflammatory cytokines on erythropoietin receptor (EpoR) messenger ribonucleic acid (mRNA) expression was investigated in this study.METHODS: Human erythroleukemia cells, TF-1 (5 x 10^6 cells/mL), were incubated with serial dilutions of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). The expression of EpoR mRNA in TF-1 cells was measured.RESULTS: EpoR mRNA transcripts in TF-1 cells were inhibited by all three cytokines in a concentration-dependent manner. The percentage of inhibition increased with treatment duration; with the maximal inhibition appearing after 16 hours of treatment. EpoR mRNA transcripts in TF-1 cells were inhibited by 44.2 ± 1.7% with IL-6 and 49.1 ± 3.8% with TNF-α after 16-hour incubation with 200 units/mL of individual cytokine.CONCLUSION: The obtained results showed that proinflammatory cytokine-induced decrease of EpoR in erythroid progenitor cells may be one of the major causes of anemia in patients with chronic kidney and inflammatory diseases.