ABSTRACT
PURPOSE: This study aimed to evaluate the clinical findings in pediatric rhabdomyolysis and the predictive factors for acute kidney injury (AKI) in Korean children. METHODS: Medical records of 39 Korean children, who were newly diagnosed with rhabdomyolysis from January 2008 to December 2015, were retrospectively analyzed. The diagnosis was made from the medical history, elevated serum creatinine kinase level >1,000 IU/L, and plasma myoglobin level >150 ng/mL. Patients with muscular dystrophy and myocardial infarction were excluded. RESULTS: The median patient age at diagnosis was 14.0 years (range, 3–18 years), and the male to female ratio was 2.5. The most common presenting symptom was myalgia (n=25, 64.1%), and 14 patients (35.9%) had rhabdomyolysis-induced AKI. Eighteen patients (46.2%) had underlying diseases, such as epilepsy and psychotic disorders. Ten of these patients showed rhabdomyolysis-induced AKI. The common causes of rhabdomyolysis were infection (n=12, 30.7%), exercise (n=9, 23.1%), and trauma (n=8, 20.5%). There was no difference in the distribution of etiology between AKI and non-AKI groups. Five patients in the AKI group showed complete recovery of renal function after stopping renal replacement therapy. The median length of hospitalization was 7.0 days, and no mortality was reported. Compared with the non-AKI group, the AKI group showed higher levels of peak creatinine kinase and myoglobin, without statistical significance. CONCLUSION: The clinical characteristics of pediatric rhabdomyolysis differ from those observed in adult patients. Children with underlying diseases are more vulnerable to rhabdomyolysis-induced AKI. AKI more likely develops in the presence of a high degree of albuminuria.
Subject(s)
Adult , Child , Female , Humans , Male , Acute Kidney Injury , Albuminuria , Creatinine , Diagnosis , Epilepsy , Hospitalization , Medical Records , Mortality , Muscular Dystrophies , Myalgia , Myocardial Infarction , Myoglobin , Phosphotransferases , Plasma , Psychotic Disorders , Renal Replacement Therapy , Retrospective Studies , RhabdomyolysisABSTRACT
Subject(s)
Humans , Basal Cell Nevus Syndrome , Carcinoma, Basal Cell , Hypertelorism , Mass Screening , Odontogenic Cysts , PenetranceABSTRACT
In vivo electroporation has emerged as a leading technology for developing nonviral gene therapies, and the various technical parameters governing electroporation efficiency have been optimized by both theoretical and experimental analysis. However, most electroporation parameters focused on the electric conditions and the preferred vehicle for plasmid DNA injections has been normal saline. We hypothesized that salts in vehicle for plasmid DNA must affect the efficiency of DNA transfer because cations would alter ionic atmosphere, ionic strength, and conductivity of their medium. Here, we show that half saline (71 mM) is an optimal vehicle for in vivo electroporation of naked DNA in skeletal muscle. With various salt concentrations, two reporter genes, luciferase and beta-galactosidase were injected intramuscularly under our optimal electric condition (125 V/cm, 4 pulses x 2 times, 50 ms, 1 Hz). Exact salt concentrations of DNA vehicle were measured by the inductively coupled plasma-atomic emission spectrometer (ICP-AES) and the conductivity change in the tissue induced by the salt in the medium was measured by Low-Frequency (LF) Impedance Analyzer. Luciferase expression in-creased as cation concentration of vehicle dec-reased and this result can be visualized by X-Gal staining. However, at lower salt concentration, transfection efficiency was diminished because the hypoosmotic stress and electrical injury by low conductivity induced myofiber damage. At optimal salt concentration (71 mM), we observed a 3-fold average increase in luciferase expression in comparison with the normal saline condition (p < 0.01). These results provide a valuable experimental parameter for in vivo gene therapy mediated by electroporation.
Subject(s)
Animals , Female , Mice , Comparative Study , DNA/administration & dosage , Drug Delivery Systems , Electric Conductivity , Electroporation/methods , Escherichia coli/genetics , Genetic Therapy/methods , Gene Transfer Techniques , Genes, Reporter , Injections, Intramuscular , Luciferases/metabolism , Mice, Inbred BALB C , Muscle, Skeletal/drug effects , Osmolar Concentration , Plasmids/genetics , Sodium Chloride/pharmacology , Transfection , Pharmaceutical Vehicles/administration & dosage , beta-Galactosidase/metabolismABSTRACT
In vivo electroporation has emerged as a leading technology for developing nonviral gene therapies, and the various technical parameters governing electroporation efficiency have been optimized by both theoretical and experimental analysis. However, most electroporation parameters focused on the electric conditions and the preferred vehicle for plasmid DNA injections has been normal saline. We hypothesized that salts in vehicle for plasmid DNA must affect the efficiency of DNA transfer because cations would alter ionic atmosphere, ionic strength, and conductivity of their medium. Here, we show that half saline (71 mM) is an optimal vehicle for in vivo electroporation of naked DNA in skeletal muscle. With various salt concentrations, two reporter genes, luciferase and beta-galactosidase were injected intramuscularly under our optimal electric condition (125 V/cm, 4 pulses x 2 times, 50 ms, 1 Hz). Exact salt concentrations of DNA vehicle were measured by the inductively coupled plasma-atomic emission spectrometer (ICP-AES) and the conductivity change in the tissue induced by the salt in the medium was measured by Low-Frequency (LF) Impedance Analyzer. Luciferase expression in-creased as cation concentration of vehicle dec-reased and this result can be visualized by X-Gal staining. However, at lower salt concentration, transfection efficiency was diminished because the hypoosmotic stress and electrical injury by low conductivity induced myofiber damage. At optimal salt concentration (71 mM), we observed a 3-fold average increase in luciferase expression in comparison with the normal saline condition (p < 0.01). These results provide a valuable experimental parameter for in vivo gene therapy mediated by electroporation.
Subject(s)
Animals , Female , Mice , Comparative Study , DNA/administration & dosage , Drug Delivery Systems , Electric Conductivity , Electroporation/methods , Escherichia coli/genetics , Genetic Therapy/methods , Gene Transfer Techniques , Genes, Reporter , Injections, Intramuscular , Luciferases/metabolism , Mice, Inbred BALB C , Muscle, Skeletal/drug effects , Osmolar Concentration , Plasmids/genetics , Sodium Chloride/pharmacology , Transfection , Pharmaceutical Vehicles/administration & dosage , beta-Galactosidase/metabolismABSTRACT
Direct injection of the vascular endothelial growth factor (VEGF) gene plasmid DNA into the myocardium was shown to induce development of new blood vessels to increase the circulation in the heart of patients with coronary artery diseases. However, such angiogenic gene therapy (via naked DNA) was limited by low level of gene expression. Furthermore, the temporal and spatial characteristics of VEGF gene transfer in the heart are not known. In this study, we demonstrated that a plasmid vector, containing the human cytomegalovirus immediate early (HCMV IE) promoter and enhancer, induces greater expression of gene in the rat heart monitored by gene fused to the chloramphenicol acetyl transferase (CAT) reporter, than four different viral and cellular promoters. Interestingly, expression of VEGF121 protein showed an earlier peak, a shorter duration, and a wider distribution than that of CAT only. Therefore, a plasmid vector with an HCMV IE promoter/enhancer provides clear advantages over other previously developed plasmids. Furthermore, expression profile of VEGF121 gene may provide useful information in the design of angiogenic gene therapy in the heart
Subject(s)
Animals , Male , Rats , Chloramphenicol O-Acetyltransferase/analysis , Comparative Study , Cytomegalovirus/genetics , DNA, Viral/administration & dosage , Endothelial Growth Factors/analysis , Enhancer Elements, Genetic , Gene Expression Regulation, Viral , Gene Fusion , Gene Transfer Techniques , Genes, Viral , Genetic Vectors , Intercellular Signaling Peptides and Proteins/analysis , Lymphokines/analysis , Myocardium/metabolism , Plasmids/genetics , Promoter Regions, Genetic , Rats, Sprague-Dawley , Time Factors , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth FactorsABSTRACT
Direct injection of the vascular endothelial growth factor (VEGF) gene plasmid DNA into the myocardium was shown to induce development of new blood vessels to increase the circulation in the heart of patients with coronary artery diseases. However, such angiogenic gene therapy (via naked DNA) was limited by low level of gene expression. Furthermore, the temporal and spatial characteristics of VEGF gene transfer in the heart are not known. In this study, we demonstrated that a plasmid vector, containing the human cytomegalovirus immediate early (HCMV IE) promoter and enhancer, induces greater expression of gene in the rat heart monitored by gene fused to the chloramphenicol acetyl transferase (CAT) reporter, than four different viral and cellular promoters. Interestingly, expression of VEGF121 protein showed an earlier peak, a shorter duration, and a wider distribution than that of CAT only. Therefore, a plasmid vector with an HCMV IE promoter/enhancer provides clear advantages over other previously developed plasmids. Furthermore, expression profile of VEGF121 gene may provide useful information in the design of angiogenic gene therapy in the heart