Remission of Proteinuria May Protect against Progression to Chronic Kidney Disease in Pediatric-Onset IgA Nephropathy.

Immunoglobulin A nephropathy (IgAN) is one of the most common primary glomerulopathies diagnosed in children and adolescents. This study aimed to evaluate the clinical features in and outcomes of pediatric IgAN over the last 30 years. Patients who were diagnosed before age of 18 at 20 centers in Korea were evaluated retrospectively. Of the 1154 patients (768 males, 386 females) with a median follow-up of 5 years, 5.6% (n = 65) progressed to stage 3-5 chronic kidney disease (CKD). The 10- and 20-year CKD-free survival rates were 91.2% and 75.6%, respectively. Outcomes did not differ when comparing those in Korea who were diagnosed prior to versus after the year 2000. On multivariate analysis, combined asymptomatic hematuria and proteinuria as presenting symptoms and decreased renal function at the time of biopsy were associated with progression to CKD, while remission of proteinuria was negatively associated with this outcome. Patients who presented with gross hematuria or nephrotic syndrome tended toward positive outcomes, especially if they ultimately achieved remission. While remission of proteinuria might imply that the disease is inherently less aggressive, it also can be achieved by management. Therefore, more aggressive management might be required for pediatric-onset IgAN.

Mesenchymal stem cells attenuate adriamycin-induced nephropathy by diminishing oxidative stress and inflammation via downregulation of the NF-kB.

AIM: This study aimed to evaluate the molecular mechanism mitigating progress of chronic nephropathy by mesenchymal stem cells (MSCs). METHODS: Rats were divided into normal control (Normal), adriamycin (ADR)+vehicle (CON), and ADR+MSC (MSC) groups. Nephropathy was induced by ADR (4 mg/kg) and MSCs (2 × 106 ) were injected. Rats were euthanized 1 or 6 weeks after ADR injection. NF-kB, MAPKs, inflammation, oxidative stress, profibrotic molecules, and nephrin expression were evaluated. Electron and light microscopy were used for structural analysis. MSCs were co-cultured with renal tubular epithelial cells or splenocytes to evaluate relation with oxidative stress and inflammatory molecules RESULTS: Adriamycin treatment upregulated inflammation, oxidative stress, and profibrotic molecules; this was mitigated by MSCs. Glomerulosclerosis and interstitial fibrosis were observed in ADR-treated groups, and were more prominent in the CON group than in the MSC group. Fusion of foot processes and loss of slit diaphragms were also more prominent in the CON group than in the MSC group. In vitro, MSCs reduced oxidative stress related molecules, inflammatory cytokines, and NF-kB transcription. MSC- or ADR-induced regulation of NF-kB transcriptional activity was confirmed by a luciferase reporter assay. CONCLUSIONS: Mesenchymal stem cells attenuate ADR-induced nephropathy by diminishing oxidative stress and inflammation via downregulation of NF-kB.

Long-term renal outcome in children with OCRL mutations: retrospective analysis of a large international cohort.

Background: Lowe syndrome (LS) and Dent-2 disease (DD2) are disorders associated with mutations in the OCRL gene and characterized by progressive chronic kidney disease (CKD). Here, we aimed to investigate the long-term renal outcome and identify potential determinants of CKD and its progression in children with these tubulopathies. Methods: Retrospective analyses were conducted of clinical and genetic data in a cohort of 106 boys (LS: 88 and DD2: 18). For genotype-phenotype analysis, we grouped mutations according to their type and localization. To investigate progression of CKD we used survival analysis by Kaplan-Meier method using stage 3 CKD as the end-point. Results: Median estimated glomerular filtration rate (eGFR) was lower in the LS group compared with DD2 (58.8 versus 87.4 mL/min/1.73 m2, P < 0.01). CKD stage II-V was found in 82% of patients, of these 58% and 28% had moderate-to-severe CKD in LS and DD2, respectively. Three patients (3%), all with LS, developed stage 5 of CKD. Survival analysis showed that LS was also associated with a faster CKD progression than DD2 (P < 0.01). On multivariate analysis, eGFR was dependent only on age (b = -0.46, P < 0.001). Localization, but not type of mutations, tended to correlate with eGFR. There was also no significant association between presence of nephrocalcinosis, hypercalciuria, proteinuria and number of adverse clinical events and CKD. Conclusions: CKD is commonly found in children with OCRL mutations. CKD progression was strongly related to the underlying diagnosis but did not associate with clinical parameters, such as nephrocalcinosis or proteinuria.

Recombinant Human Erythropoietin Therapy for a Jehovah's Witness Child With Severe Anemia due to Hemolytic-Uremic Syndrome.

Patients with hemolytic-uremic syndrome (HUS) can rapidly develop profound anemia as the disease progresses, as a consequence of red blood cell (RBC) hemolysis and inadequate erythropoietin synthesis. Therefore, RBC transfusion should be considered in HUS patients with severe anemia to avoid cardiac or pulmonary complications. Most patients who are Jehovah's Witnesses refuse blood transfusion, even in the face of life-threatening medical conditions due to their religious convictions. These patients require management alternatives to blood transfusions. Erythropoietin is a glycopeptide that enhances endogenous erythropoiesis in the bone marrow. With the availability of recombinant human erythropoietin (rHuEPO), several authors have reported its successful use in patients refusing blood transfusion. However, the optimal dose and duration of treatment with rHuEPO are not established. We report a case of a 2-year-old boy with diarrhea-associated HUS whose family members are Jehovah's Witnesses. He had severe anemia with acute kidney injury. His lowest hemoglobin level was 3.6 g/dL, but his parents refused treatment with packed RBC transfusion due to their religious beliefs. Therefore, we treated him with high-dose rHuEPO (300 IU/kg/day) as well as folic acid, vitamin B12, and intravenous iron. The hemoglobin level increased steadily to 7.4 g/dL after 10 days of treatment and his renal function improved without any complications. To our knowledge, this is the first case of successful rHuEPO treatment in a Jehovah's Witness child with severe anemia due to HUS.

Does the use of bedside ultrasonography reduce emergency department length of stay for patients with renal colic?: a pilot study.

OBJECTIVE: The aim of this study was to evaluate the effect of adding bedside ultrasonography to the diagnostic algorithm for nephrolithiasis on emergency department (ED) length of stay. METHODS: A prospective, randomized, controlled pilot study was conducted from October 2014 to December 2014 with patients with acute flank pain. In the non-ultrasonography group (NUSG), non-contrast computed tomography was selected based on clinical features and hematuria in the urinalysis. In the ultrasonography group (USG), non-contrast computed tomography was selected based on clinical features and hydronephrosis on bedside ultrasonography. The primary outcome was ED length of stay. The secondary outcomes were radiation exposure, amount of analgesics, proportion of patients with diseases other than ureteral calculus, and proportion of patients with unexpected ED revisits within 7 days from the index visit. RESULTS: A total of 103 patients were enrolled (NUSG, 51; USG, 52). The ED length of stay for the USG (89.0 minutes) was significantly shorter than that for the NUSG (163.0 minutes, P<0.001). There were no significant differences between the two groups in the radiation exposure dose (5.29 and 5.08 mSv, respectively; P=0.392), amount of analgesics (P=0.341), proportion of patients with diseases other than ureteral calculus (13.0% and 6.8%, respectively; P=0.486), and proportion of patients with unexpected ED revisits within 7 days from the index visit (7.8% and 9.6%, respectively; P=1.000). CONCLUSION: The use of early bedside ultrasonography for patients with acute flank pain could reduce the ED length of stay without increasing unexpected ED revisits.

Atypical hemolytic uremic syndrome: Korean pediatric series.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare disease with a genetic predisposition. Few studies have evaluated the disease in the Asian population. We studied a Korean pediatric cohort to delineate the clinical characteristics and genotypes. METHODS: A multicenter cohort of 51 Korean children with aHUS was screened for mutations using targeted exome sequencing covering 46 complement related genes. Anti-complement-factor-H autoantibody (anti-CFH) titers were measured. Multiplex ligation-dependent probe amplification assay was performed to detect deletions in the complement factor-H related protein genes (CFHR) in the patients as well as in 100 healthy Korean controls. We grouped the patients according to etiology and compared the clinical features using Mann-Whitney U-test and chi-squared test. RESULTS: Fifteen patients (group A, 29.7%) had anti-CFH, and mutations were detected in 11 (group B, 21.6%), including one with combined mutations. The remaining 25 (group C, 49.0%) were negative for both. The prevalence of anti-CFH was higher than the worldwide level. Group A had a higher onset age than group B, although the difference was not significant. Group B had the worst renal outcome. Gene frequencies of homozygous CFHR1 deletion were 73.3%, 2.7% and 1% in group A, group B + C and the control, respectively. CONCLUSIONS: The incidence of anti-CFH in the present Korean aHUS cohort was high. Clinical outcomes largely conformed to the previous reports. Although the sample size was limited, this cohort provides a reassessment of clinicogenetic features of aHUS in Korean children.

Atypical retinopathy in patients with nephronophthisis type 1: an uncommon ophthalmological finding.

BACKGROUND: Progressive retinal degeneration without retinal pigmentation has been repeatedly observed in Korean nephronophthisis (NPHP) type 1 patients with a total homozygous deletion of NPHP1. DESIGN: Retrospective case series. PARTICIPANTS: Patients with clinical diagnosis of NPHP and genetic diagnosis of total deletion of NPHP1 (n = 5) were included in this study. METHODS: Patients with clinical diagnosis of NPHP (n = 57) were screened for total deletion of NPHP1 by polymerase chain reaction (PCR) for the 20 exons of NPHP1. The clinical and ophthalmological findings of NPHP type 1 patients were reviewed. Additionally, four exons of MALL, a gene adjacent to NPHP1, were amplified using PCR, and amplification failure was considered a homozygous deletion encompassing the corresponding exons. MAIN OUTCOME MEASURE: Ophthalmological findings in NPHP type 1 patients. RESULTS: Five of 57 patients with clinical diagnosis of NPHP were diagnosed as having NPHP type 1 by genetic analysis. Chronic renal failure was diagnosed in these five patients at 7.9-15.4 years of age. All the patients with NPHP type 1 had progressive decline in visual acuity with various ages of onset (2-17 years). Ophthalmological examinations revealed unexpected findings of retinopathy with large or small flecks, which was compatible with Stargardt-like retinopathy or albipunctatus retinopathy in majority of them (four of five). The genetic study revealed an additional deletion of exon 1 of the adjacent gene MALL. CONCLUSIONS: We report the unexpectedly common retinal involvement of NPHP type 1 with an additional MALL deletion in a Korean cohort.

Human adipose-derived stem cells attenuate inflammatory bowel disease in IL-10 knockout mice.

Inflammatory bowel disease (IBD) is a complex immunological disorder characterized by chronic inflammation caused mainly by unknown factors. The interleukin-10 knockout (IL-10 KO) mouse is a well-established murine model of IBD which develops spontaneous intestinal inflammation that resembles Crohn's disease. In the present study, human adipose-derived mesenchymal stem cells (hAMSCs) were administrated to IL-10 KO mice to evaluate the anti-inflammatory effects of hAMSCs that may attenuate the progress of or treat IBD. After IBD was induced by feeding the IL-10 KO mouse a 125-250 ppm piroxicam mixed diet for 1 week, 2×10(6) hAMSCs were injected into the peritoneum and the mice were switched to a normal diet. After 1 week, the mice were sacrificed and tissue samples were harvested. Tissue scores for inflammation and inflammation-related genes expression were determined. The hAMSC-treated group showed significantly reduced inflammatory changes in histological analysis. Reverse transcription-PCR analysis showed that RANTES, Toll-like receptor 9, and IL-4 expression levels were not significantly different between the groups while IL-12, INF-γ, and TNF-α levels were significantly decreased in the hAMSC treated group. hAMSC attenuated IBD in the IL-10 KO mice by suppressing inflammatory cytokine expression, was mediated by the type 1 helper T cell pathway. Even though only a single injection of hAMSCs was delivered, the effect influenced chronic events associated with inflammatory changes and demonstrated that hAMSCs are a powerful candidate for IBD therapy.

Refractory acute suppurative thyroiditis secondary to pyriform sinus fistula.

Acute suppurative thyroiditis is a rare disease because the thyroid gland is remarkably resistant to infection. We present a 2-year-old girl with refractory acute suppurative thyroiditis due to a pyriform sinus fistula (PSF). She complained of fever and painful anterior neck swelling. Her condition did not completely improved by multiple parenteral antibiotics along with incision and drainage. Barium esophagogram to detect PSF demonstrated no specific finding. Computed tomography scan showed air bubble superior to the left thyroid gland which indicated a possible fistula connected to the pyriform sinus. An intraoperative laryngoscopy revealed a 2-mm-sized fistula opening. The fistula was successfully treated by chemocauterization with trichloroacetic acid.

Muscle involvement in Dent disease 2.

BACKGROUND: Dent disease, an X-linked recessive renal tubulopathy, is caused by mutations in either CLCN5 (Dent disease 1) or OCRL (Dent disease 2). OCRL mutations can also cause Lowe syndrome. In some cases it is difficult to differentiate Dent disease 1 and 2 on the basis of clinical features only without genetic tests. Several studies have shown differences in serum levels of muscle enzymes between these diseases. The aim of our study was to test the validity of these findings. METHODS: In total, 23 patients with Dent disease 1 (Group A), five patients with Dent disease 2 (Group B) and 19 patients with Lowe syndrome (Group C) were enrolled in our study. The serum levels of three muscle enzymes [creatine phosphokinase (CPK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST)], were measured. The levels of a hepatic enzyme, alanine aminotransferase (ALT), were also measured as a control. RESULTS: One patient in Group B had muscle hypoplasia of both upper extremities. The serum levels of all three muscle enzymes assayed were higher in Group B or C patients than in Group A patients. Serum ALT levels were normal in all three groups of patients. CONCLUSIONS: The serum levels of muscle enzymes in patients with Dent disease can be used as a biomarker to predict genotypes, even though the patients do not have clinical symptoms of muscle involvement.

CST recovery in pediatric hemiplegic patients: Diffusion tensor tractography study.

Many diffusion tensor imaging (DTI) studies have reported an association between corticospinal tract (CST) injury and motor dysfunction. In this study, we investigated CST recovery in 29 pediatric patients with clinical hemiplegia using DTI. We measured the fractional anisotropy (FA), apparent diffusion coefficient (ADC), and asymmetric anisotropy (AA) of both CSTs. The patients were classified into three groups according to severity of CST disruption of the more affected hemisphere. DTI was followed up for 9.34 ± 2.07 months after initial evaluation. The FA value of the more affected CST showed a significant decrease compared to the opposite side at initial and follow up evaluation, respectively (p<0.05). The FA value of both CSTs showed a significant increase at follow up compared to the initial evaluation, while more changes were observed on the more affected side, compared with the less affected side (p<0.05). AA showed a significant decrease at follow up, and showed significant correlation with interval change of FA value of the more affected side, not with that of the less affected side (r=0.543, p<0.05). 19 patients showed change of CST integrity. In the current study, the results of DTI showed recovery of the CST and provided radiologic evidence for a scientific basis of brain plasticity in pediatric patients.

A nationwide epidemiological study of nocturnal enuresis in Korean adolescents and adults: population based cross sectional study.

We performed a nationwide epidemiological study to evaluate the prevalence and characteristics of nocturnal enuresis (NE) in Korean adolescents and adults. A questionnaire was sent via e-mail to 51,073 people aged 16-40 yr by stratified sampling according to age, sex, and region among a 200,000 internet survey panel pool. The questionnaire included following information; presence or absence of NE, frequency of NE, possible risk factors for NE, self-esteem scale score and depression score results, and measures for the treatment of NE. Among the 2,117 responders, 54 (2.6%) had NE (≥1 enuretic episode within 6 months). Of 54 bedwetters, 9.3% wet ≥1 night per week and 20.5% wet ≥1 per month. The prevalence rates remained relatively stable with no apparent trend of reduction with age. The presence of sleep disturbance, family history, urgency, or urge incontinence increased the probability of NE episode significantly. The self-esteem score was lower (P=0.053) and the depression scale score was higher (P=0.003) in bedwetters compared with non-bedwetters. Overall 2.6% of Korean aged 16-40 yr have NE. The higher rate of urgency and urge incontinence in adolescent and adult enuretics suggests that bladder function has an important role in adolescent and adult NE.

Clinical characteristics of Kawasaki disease with sterile pyuria.

PURPOSE: Kawasaki disease (KD) is a systemic vasculitis and affects many organ systems. It often presents sterile pyuria, microscopic hematuria, and proteinuria due to renal involvement. The aims of this study were to define clinical characteristics of acute KD patients with pyuria and to analyze meaning of pyuria in KD. METHODS: The medical records and laboratory findings including serum and urine test of 133 patients with KD admitted to Yeungnam University Hospital from March 2006 to December 2010 were reviewed retrospectively. RESULTS: Forty patients had sterile pyuria and their clinical characteristics including age, gender and body weight were not significantly different with those who did not have pyuria. Fever duration after treatment was significantly longer in KD patients with pyuria. Erythrocyte sedimentation rate, C-reactive protein and serum concentration of alanine aminotransferase were significantly higher in patients with pyuria. Hyponatremia and coronary artery lesion were seen more often in patients with pyuria but there was no significant difference. Also serum blood urea nitrogen was significantly higher in KD patients with pyuria. Urine ß(2)-microglobulin was elevated in both patients groups and showed no difference between two groups. CONCLUSION: We found more severe inflammatory reaction in KD patients with pyuria. We also found elevation of some useful parameters like ß(2)-microglobulin that indicate renal involvement of KD through the urine test. Careful management and follow up will need for KD patients with pyuria and it is necessary in the future to study the specific parameters for renal involvement of KD.

Significance of electron dense deposits in patients with minimal change nephrotic syndrome.

BACKGROUND: Minimal change nephritic syndrome (MCNS) is characterized by a lack of obvious abnormalities on light microscopy, but its electron microscopic findings include the negative immunofluorescence findings and the diffuse effacement of the epithelial cell foot processes. Rarely the presence of electron dense deposits (EDDs) has been reported, but its clinical significance remains obscure. METHODS: Eleven patients with MCNS who had the EDD deposited were enrolled in the current study. We compared the clinical characteristics, laboratory results and response to steroid treatment between the two group: the EDD group (n=11; the male-to-female ratio, 8:3) and the non-EDD group (n=13, 8:5). RESULTS: There were no significant differences in most of the laboratory results or response to steroid treatment between the two groups. The frequency of relapses per year was significantly higher in the EDD group (1.1±0.7 times vs. 0.5±0.6 times; p=0.023). These EDDs were found in the mesangium or paramesangium. With no respect to the characteristics of EDDs, our results showed that they did not cause poor treatment outcomes except for the annual frequency of relapse. CONCLUSIONS: Further large-scale studies are warrented to determine the immunologic and prognostic significance of EDDs in patients with MCNS.

Dense deposit disease in Korean children: a multicenter clinicopathologic study.

The purpose of this study was to investigate the clinical, laboratory, and pathologic characteristics of dense deposit disease (DDD) in Korean children and to determine whether these characteristics differ between Korean and American children with DDD. In 2010, we sent a structured protocol about DDD to pediatric nephrologists throughout Korea. The data collected were compared with previously published data on 14 American children with DDD. Korean children had lower 24-hr urine protein excretion and higher serum albumin levels than American children. The light microscopic findings revealed that a higher percentage of Korean children had membranoproliferative glomerulonephritis patterns (Korean, 77.8%; American, 28.6%, P = 0.036), whereas a higher percentage of American children had crescents (Korean, 0%; American, 78.6%, P < 0.001). The findings from the electron microscopy revealed that Korean children were more likely to have segmental electron dense deposits in the lamina densa of the glomerular basement membrane (Korean, 100%; American, 28.6%, P = 0.002); mesangial deposit was more frequent in American children (Korean, 66.7%; American, 100%, P = 0.047). The histological findings revealed that Korean children with DDD were more likely to show membranoproliferative glomerulonephritis patterns than American children. The degree of proteinuria and hypoalbuminemia was milder in Korean children than American children.

A case of tacrolimus-induced encephalopathy after kidney transplantation.

We present a case of tacrolimus-induced encephalopathy after successful kidney transplantation. An 11-year-old girl presented with sudden onset of neurologic symptoms, hypertension, and psychiatric symptoms, with normal kidney function, after kidney transplantation. The symptoms improved after cessation of tacrolimus. Magnetic resonance imaging (MRI) showed acute infarction of the middle cerebral artery (MCA) territory in the right frontal lobe. Three days later, she had normal mental function and maintained normal blood pressure with left hemiparesis. Follow-up MRI was performed on D19, showing new infarct lesions at both cerebral hemispheres. Ten days later, MRI showed further improvement, but brain single photon emission computed tomography (SPECT) showed mild reduction of uptake in both the anterior cingulate gyrus and the left thalamus. One month after onset of symptoms, angiography showed complete resolution of stenosis. However, presenting as a mild fine motor disability of both hands and mild dysarthria, what had been atrophy at both centrum semiovale at 4 months now showed progression to encephalomalacia. There are two points of interest in this case. First, encephalopathy occurred after administration of tacrolimus and improved after discontinuation of the drug. Second, the development of right-side hemiplegia could not be explained by conventional MRI; but through diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) of white matter tract, visualization was possible.

Inhibition of beta-amyloid(1-40) Peptide Aggregation and Neurotoxicity by Citrate.

The accumulation of beta-amyloid (Abeta) aggregates is a characteristic of Alzheimer's disease (AD). Furthermore, these aggregates have neurotoxic effects on cells, and thus, molecules that inhibit Abeta aggregate formation could be valuable therapeutics for AD. It is well known that aggregation of Abeta depends on its hydrophobicity, and thus, in order to increase the hydrophilicity of Abeta, we considered using citrate, an anionic surfactant with three carboxylic acid groups. We hypothesized that citrate could reduce hydrophobicity and increase hydrophilicity of Abeta(1-40) molecules via hydrophilic/electrostatic interactions. We found that citrate significantly inhibited Abeta(1-40) aggregation and significantly protected SH-SY5Y cell line against Abeta(1-40) aggregates-induced neurotoxicity. In details, we examined the effects of citrate on Abeta(1-40) aggregation and on Abeta(1-40) aggregates-induced cytotoxicity, cell viability, and apoptosis. Th-T assays showed that citrate significantly inhibited Abeta(1-40) aggregation in a concentration-dependent manner (Th-T intensity: from 91.3% in 0.01 mM citrate to 82.1% in 1.0 mM citrate vs. 100.0% in Abeta(1-40) alone). In cytotoxicity and viability assays, citrate reduced the toxicity of Abeta(1-40) in a concentration-dependent manner, in which the cytotoxicity decreased from 107.5 to 102.3% as compared with Abeta(1-40) aggregates alone treated cells (127.3%) and the cell viability increased from 84.6 to 93.8% as compared with the Abeta(1-40) aggregates alone treated cells (65.3%). Furthermore, Hoechst 33342 staining showed that citrate (1.0 mM) suppressed Abeta(1-40) aggregates-induced apoptosis in the cells. This study suggests that citrate can inhibit Abeta(1-40) aggregation and protect neurons from the apoptotic effects of Abeta(1-40) aggregates. Accordingly, our findings suggest that citrate administration should be viewed as a novel neuroprotective strategy for AD.

Clinico-genetic study of nail-patella syndrome.

Nail-patella syndrome (NPS) is an autosomal dominant disease that typically involves the nails, knees, elbows and the presence of iliac horns. In addition, some patients develop glomerulopathy or adult-onset glaucoma. NPS is caused by loss-of-function mutations in the LMX1B gene. In this study, phenotype-genotype correlation was analyzed in 9 unrelated Korean children with NPS and their affected family members. The probands included 5 boy and 4 girls who were confirmed to have NPS, as well as 6 of their affected parents. All of the patients (100%) had dysplastic nails, while 13 patients (86.7%) had patellar anomalies, 8 (53.3%) had iliac horns, 6 (40.0%) had elbow contracture, and 4 (26.7%) had nephropathy including one patient who developed end-stage renal disease at age 4.2. The genetic study revealed 8 different LMX1B mutations (5 missense mutations, 1 frame-shifting deletion and 2 abnormal splicing mutations), 6 of which were novel. Genotype-phenotype correlation was not identified, but inter- and intrafamilial phenotypic variability was observed. Overall, these findings are similar to the results of previously conducted studies, and the mechanism underlying the phenotypic variations and predisposing factors of the development and progression of nephropathy in NPS patients are still unknown.

Poria cocos water extract (PCW) protects PC12 neuronal cells from beta-amyloid-induced cell death through antioxidant and antiapoptotic functions.

Beta-amyloid (Abeta)-induced neurotoxicity is considered to be mediated through the formation of reactive oxygen species (ROS). In this study, the protective effects of Poria cocos water extract (PCW) against Abeta1-42-induced cell death were investigated using rat pheochromocytoma (PC12) cells. Exposure of PC12 cells to the Abeta1-42 (20 microM) for 48h resulted in neuronal cell death, whereas pretreatment with PCW at the concentration range of 5-125 microg/ml reduced Abeta1-42-induced cell death. In addition, PC12 cells treated with Abeta1-42 exhibited increased accumulation of intracellular oxidative damages and underwent apoptotic death as determined by characteristic morphological alterations and positive in situ terminal end-labeling (TUNEL staining). However, PCW attenuated Abeta1-42-induced cytotoxicity, apoptotic features, and accumulation of intracellular oxidative damage. Moreover, PCW (5 to 125 microg/ml) decreased expression of apoptotic protein Bax and activity of caspase-3, but enhanced expression of anti-apoptotic protein Bcl-2. These results suggest that PCW may protect cells through suppressing the oxidative stress and the apoptosis induced by Abeta1-42, implying that PCW may be potential natural agents for Alzheimer's diseases.