ABSTRACT
PURPOSE: Immaure brain is more resistant to seizure-induced neuronal damage than the adult brain in animal study. Immediate early genes such as c-jun play a critical role in neuronal damage. Therefore, we hypothesized that the difference of constitutive and electrically stimulated c-Jun expression would explain the difference in neuronal damage from seizures between immature and mature explant culture. METHODS: Seven and 14 days-in-vitro(DIV) hippocampal explant cultures derived from 8-day-old rat pups were used. Extracellular field recording was done in cultures. A 1-sec stimulus train(60 Hz, 0.1 msec rectangular pulses) was applied to the Schaffer collaterals, and the afterdischarge was recorded in CA1 pyramidal layer. Cultures were returned to the incubator and observed serially. Intensity of propidium iodide fluorescence indicative of neuronal damage was quantitated as percent of total damage induced by 2 mM NMDA. Proteins extracted from individual cultures were analyzed by Western blot. RESULTS: Constitutive c-Jun protein expression at 7 DIV was higher than that at 14 DIV. There was not a significant difference of c-Jun expression between the 7 DIV and 14 DIV cultures after electrical stimulation. Neuronal damage after electrical stimulation in the hippocampus at 7 DIV was significantly lower than at 14 DIV. CONCLUSION: The results show reduced neuronal injury from seizures in more immature culture. However, constitutive expression of c-Jun protein was higher. Higher constitutive expression may inhibit further induction of c-Jun from seizures and thus result in less severe neuronal injury.
Subject(s)
Adult , Animals , Humans , Rats , Blotting, Western , Brain , Electric Stimulation , Fluorescence , Genes, Immediate-Early , Hippocampus , Incubators , N-Methylaspartate , Neurons , Propidium , SeizuresABSTRACT
PURPOSE: Considering that renal biopsy is not routinely indicated in nephrotic syndrome in children and the risk of the procedure, we studied that it is possible to predict steroid responsiveness in nephrotic syndrome and the difference in responsivenss is related with the histopathologic type using urinary beta2-microglobulin and N-Acetyl-beta-D-Glucosaminidase activity as a safe and noninvasive method. METHODS: We measured serum creatinine, albumin, cholesterol and urinary creatinine, protein, B2M, NAG at the time of admission and after 2 weeks of treatment in 37 cases of primary nephrotic syndrome in children who were admitted to the Pediatric department of Chung-Ang Medical Center between March 1, 1994 and June 30, 1996. RESULTS: The results were as follows : 1) When urinary B2M value of less than 1000microgram/g creatinine was used as the cut-off value, the test identified steroid responsiveness with a sensitivity of 100%, a specificity of 80%. When urinary NAG activity of less than 100U/hr/mg creatinine was used as the cut-off value, the test identified steroid responsiveness with a sensitivity of 100%, a specificity of 81.8%. 2) Pretreatment urinary B2M levels in Good-response and Poor-response group were 559.8+/-718.5microgram/g creatinine, 3599.1+/-4956.7microgram/g creatinine, respectively. There was statistical significance between the two groups (P<0.05). 3) Pretreatment urinary NAG activity in Good-response and Poor-response group were 42.6+/-23.6U/hr/mg creatinine, 79.6+/-80.1U/hr/mg creatinine, respectively. There was statistical significance between the two groups (P<0.05). CONCLUSIONS: In conclusion, measurement of urinary B2M level and NAG activity for early detection of renal tubular damage is helpful in prediction of steroid responsiveness of primary nephrotic syndrome. If the urinary B2M level and NAG activity are elevated, the patient is suspected to steroid resistance. Therefore, prolonged steroid therapy should be avoided in such patients because of their greater chance of not responding. This approach would reduce the many serious side effects of prolonged treatment in patients who are unlikely to benefit.