Effects of Angiotensin II on ZO-1 in Glomerular Epithelial Cells / 대한신장학회지

PURPOSE: Angiotensin II plays a potent role in renal injury not only by vasoconstrictive effects but also by biochemical effects. We investigated the effect of angiotensin II on ZO-1 (zonular occludens-1), a component of the slit diaphragm domain connecting slit diaphragm structure and actin cytoskeleton, in the glomerular epithelial cells (podocytes) for the glomerular damage. We tried to find that this effect could be prevented by losartan, an angiotensin II type 1 receptor blocker. METHODS: Glomerular epithelial cells were treated with various concentrations of angiotensin II and losartan. The distribution of ZO-1 was observed by confocal microscope and the change of ZO-1 expression was measured by Western blotting and RT-PCR. RESULTS: The intensities of fluorescences and bands of ZO-1 protein were decreased by angiotensin II in a dose-dependent manner by confocal microscopy and Western blot analysis, respectively. ZO-1 also moved from peripheral to inner cytoplasm and lost its linear pattern. These distributional changes of ZO-1 protein by angiotensin II were reversed by losartan in a dose-dependent manner. Angiotensin II reduced the amount and mRNA expresssion of ZO-1 which were also reversed by losartan. CONCLUSION: Angiotensin II decreases the amount of ZO-1 protein and changes its localization through angiotensin II type 1 receptor. These findings suggest that angiotensin II-added condition induces the cytoplasmic translocation and suppresses the production of ZO-1 in podocytes at transcriptional level, and could be prevented by angiotensin receptor antagonists.

High Glucose and Advanced Glycosylation Endproducts(AGE) Modulate the P-cadherin Expression in Glomerular Epithelial Cells(GEpC)

PURPOSE: Podocytes are critical in maintaining the filtration barrier of the glomerulus and are dependent on the integrity of slit diaphragm(SD) proteins including nephrin, P-cadherin, and others. Diabetic proteinuric condition demonstrates defects in SD molecules as well as ultrastructural changes in podocytes. We examined the molecular basis for this alteration of SD molecules especially on P-cadherin as a candidate regulating the modulation of pathogenic changes in the barrier to protein filtration. METHODS: To investigate whether high glucose and AGE induce changes in SD, we cultured rat GEpC under normal(5 mM) or high glucose(30 mM) and AGE- or BSA-added conditions and measured the change of P-cadherin expression by Western blotting and RT- PCR. RESULTS: We found that administration of high glucose decreased the P-cadherin production significantly in the presence or absence of AGE by Western blotting. In RT-PCR high glucose with or without AGE also significantly decreased the expression of P-cadherin mRNA compared to those of controls. Such changes were not seen in the osmotic control. CONCLUSION: We suggest that high glucose with or without AGE suppresses the production of P-cadherin at the transcriptional level and that these changes may explain the functional changes of SD in diabetic conditions.

A Clinical Study of Childhood Henoch-Schonlein Purpura

PURPOSE: Henoch-Schonlein purpura(HSP) is a systemic vasculitis, characterized by cutaneous purpura, abdominal pain, arthralgia and renal involvement. The clinical features of HSP have been reasonably well documented but there are still many gaps in our understanding of HSP. The aim of this study was to present the clinical features of 125 children with HSP and compare them with previous reports, placing particular emphasis on clinical information. METHODS: We collected the clinical data of 125 patients with acute HSP who visited Chungbuk National University Hospital from March 1992 to April 2002. Data were expressed as the mean or mean +/-SD and statistical analysis was performed using Chi-square approximation. P<0.05 was considered as significant. RESULTS: The patient population consisted of 87 boys and 38 girls ranging in age from one to 14 years. HSP occurs throughout the year, but this study shows seasonal skewing, with most patients presenting from fall through spring and a paucity of cases in summer. All patients had non-throm bocytopenic purpura concentrated on the buttocks and lower extremities. Purpuric lesions were also scattered on the arms and occaisionally on the face and ears, but the trunk was largely spared. A recurrence of purpura was defined as the reappearance of a rash or other symptoms following resolution of disease for at least two weeks. The mean number of recurrences was 0.51. Eighty eight patients(70.4%), 18 patients(14.4%) and 67 patients(53.6%) complained of abdomianl pain, gastroin testinal bleeding and arthralgia, respectively. Nephritis occurred in 48(38.4%) patients. Fifteen boys (17.2%) developed epididymitis. Neurologic features occurred in 13(10.4%) and two(15%) of these were seizures. CONCLUSION: HSP all showing purpura as defined is characterized by various clinical features, including abdominal pain, arthralgia, epididymitis and nephritis which could occur before the appearance of purpura. Therefore, we suggest that the possibility of HSP should be considered in children before invasive procedures, even if the above symptoms and signs present without purpura.

The Analysis of Renal Risk Factors in Henoch-Schonlein Purpura / 대한신장학회잡지

PURPOSE: Henoch-Schonlein purpura (HSP) is a multisystem disorder affecting predominantly skin, gastrointestinal tract, joint and kidneys, as well as the central nervous, cardiopulmonary and musculoskeletal system. Most patients with renal involvement have a good prognosis. However, some patients develop end-stage renal disease. Therefore, severity of renal involvement is considered to contribute to the outcome. The aim of this study was to evaluate the clinical renal risk and prognostic factors of HSP. METHODS: We had collected the clinical and laboratory data of 125 patients with acute HSP who visited Chungbuk National University Hospital from March 1992 to April 2002. Data were expressed as the mean+/-SD and statistical analysis was performed using Wilcoxon rank sum test, Mantel-Haenszel test, Fisher's Exact test, Student t-test. p<0.05 was considered as significant. RESULTS: The patient population consisted of 87 boys and 38 girls ranging from 1 to 14 years in age. Recurrance number of purpura in the HSP patients with renal involvement were significantly higher than those without renal involvement (p<0.01). 24-hour urine protein/creatinine ratio in the HSP patients with renal involvement were significantly higher than those without renal involvement (p< 0.01). But serum C3, C4, CH50, anti-streptolysin titers and so forth had no correlation with renal involvement. In the HSN patients, 24-hour creatinine and creatinine clearance have no correlation with renal involvement. Fifteen of 87 boys (17.2%) in this study developed scrotal involvement, which showed no significantly difference in patients with or without renal involvement. CONCLUSION: It is important that 24-hour urine protein/creatinine ratio at acute stage shows a significant relation with renal involvement. Results suggest that recurrence number of purpura are important to renal involvement in HSP. Based on these findings, futher prospective and/or controlled studies among more patients are thus necessary in order to prevent renal involvement in HSP.

A Case of Chronic Tubulointerstitial Nephritis in Methylmalonic Acidemia / 대한신장학회잡지

Methylmalonic acidemia (MMA) is a heterogeneous inborn error of propionate metabolism and its management frequently includes a low-protein diet to minimize precursors of methylmalonic acid and reduce its concentration in body tissues. In the long- term follow-up, renal dysfunction in these patients has been increasingly recognized. Tubulointerstitial nephritis is the most frequent renal complications and has been reported in the small number of renal biopsy specimens from young children previously by others. We report a case of a 18-year-old girl with MMA and renal dysfunction in whom renal biopsy demonstrated chronic tubulointerstitial nephritis.

Clinical Study of the Correlation of Tumor Necrosis Factor alpha and the Proteinuria of Henoch-Schonlein Nephritis and Idiopathic Nephrotic Syndrome

PURPOSE: It is not clear that the development of glomerular injury and aggravation by tumor necrosis factor alpha (TNF-alpha) is related to intrarenal or serum concentration of TNF-alpha. So, we studied the relationship between the concentration of TNF-alpha and aggravation of glomerular damage in the Henoch-Schonlein nephritis(HSN) and idiopathic nephrotic syndrome(INS). METHODS: We collected the sera and urines of 21 patients with Henoch-Schonlein purpura(HSP) and 22 patients with INS visited Chungbuk National University hospital from March 1998 to March 2001. The concentration of TNF-alpha in the sera and urines were measured by sandwich ELISA. RESULTS: Serum TNF-alpha levels in the HSP patients with renal involvement were significantly higher than those without renal involvement(P=0.009). But urine TNF-alpha levels have no correlation with renal involvement(P=0.088). In the HSN patients, proteinuria have a significant correlation with serum TNF-alpha levels(P=0.004) but less correlation with urine TNF-alpha levels(P=0.053). Otherwise, proteinuria have no correlation with serum TNF-alpha levels(P=0.763) but have a significant correlation with urine TNF-alpha levels(P=0.007) in INS. CONCLUSION: These result suggest that the serum concentration of TNF-alpha would be important to glomerular involvement in HSP. And, it is interesting that proteinuria shows a significant relation with serum TNF-alpha levels in the HSN, but with urine TNF-alpha levels in the INS. This means the major production of TNF-alpha may be originated by extrarenal inflammation in the HSN and by intrarenal tubulo-interstitial damage due to proteinuria in the INS.

A Case of Status Epilepticus Caused by a Venous Angioma of Brain / 대한소아신경학회지

Venous malformations has been shown to be the most common intracranial vascular malformation autopsy and clinical series. Cerebral venous malformation is associated with different frequnecies of epileptic seizures. Only in about 25% of cases are venous malformation diagnosed because of the occurrence of epileptic seizures. We report a case of 4 year-old female patient with status epilepticus caused by venous angioma in the right temporal lobe of the brain.

Two Cases of Acute Encephalopathy with Thalamotegmental Involvement and Remained Motor Dysfunction in Infants / 대한소아신경학회지

Acute encephalopathy with thalamotegmental involvement occurs in infants and young children and is thought to be a postviral or postinfectious brain disease. This disease is preceded for several days by fever and symptoms of upper respiratory infection. The symptoms are followed by the rapid evolution of stupor and coma, associated with generalized seizures and decerebrate rigidity. In this disease, the computed tomography (CT) or brain magnetic resonance imaging demonstrate symmetrical focal lesions in the thalami and brainstem tegmentum. We report two cases of acute encephalopathy with thalamotegmental involvement and remaining motor dysfunction in infants.