Mutations in NPHS2 in familial steroid-resistant nephrotic syndrome in Southern Chinese Han ethnic group / 中华儿科杂志

<p><b>OBJECTIVE</b>Mutations in NPHS2 mapped to 1q25-q31 and encoding podocin, which is exclusively expressed in glomerular podocytes, are responsible for autosomal recessive familial steroid-resistant nephrotic syndrome (SRNS) with minor glomerular abnormalities or focal segmental glomerulosclerosis. Different groups from European and North American countries have screened NPHS2 mutations in familial SRNS with recessive inheritance, documenting a mutation detection rate of 45% - 55% in families. This study aimed to examine mutations in the NPHS2 gene in Southern Chinese Han ethnic group patients with familial SRNS.</p><p><b>METHODS</b>Genomic DNA from 3 probands from Southern Chinese Han families with autosomal recessive SRNS, and their siblings and parents was isolated and analyzed for all eight exons, exon-intron boundaries and promoter of NPHS2 using the polymerase chain reaction and direct sequencing.</p><p><b>RESULTS</b>No mutation of NPHS2 in all eight exons and exon-intron boundaries was identified in the 3 probands. However, a polymorphism of 954T > C in exon 8 was detected in all the 3 probands and some controls, and 5 variants of NPHS2 promoter, -1709G > A, -1000A > T, -670C > T, -116C > T and -51G > T, were identified in some patients and controls, indicating that these variants are polymorphisms. One heterozygous variant of NPHS2 promoter, -1715A > G, was also identified in one proband and her mother whose urinalyses were normal, whereas it was not found in any of the 50 controls. There was no significant difference in the allelic frequencies of -1709G > A, -1000A > T, -670C > T, -116C > T and -51G > T polymorphisms between the patients and controls.</p><p><b>CONCLUSION</b>NPHS2 mutations are not a major cause of familial steroid-resistant nephrotic syndrome in Southern Chinese Han ethnic group included in the study.</p>

Neuroprotective effects of topiramate and folic acid on young rats with kindling-induced epilepsy / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the neuroprotective effects of topiramate (TPM) alone or together with folic acid (FA) on young rats with kindling-induced epilepsy.</p><p><b>METHODS</b>Rat models of epilepsy were prepared by pentylenetetrazol (PTZ)-induced kindling. Seventy-two 3-week-old male Wistar rats were randomly divided into 6 groups: four TPM-treated epilepsy groups (TPM 20, 40 or 80 mg/kg/d and TPM 40 mg/kg/d + FA 5 mg/kg/d), a positive control group (untreated epilepsy group) and a negative control group (normal control group). After two months of administration, behaviors of the rats were recorded; serum levels of neuron-specific enolase (NSE) were measured using ELISA; pathological changes in the hippocampus were observed.</p><p><b>RESULTS</b>The frequency of convulsion seizures in the 20, 40 and 80 mg TPM treatment and TPM+FA groups was 44.7 +/- 2.9, 44.3 +/- 3.1, 42.7 +/- 3.2, and 40.8 +/- 3.7 respectively, which were significantly lower than that in the positive control group (48.4 +/- 3.7) (P <0.01). Twenty, forty and eighty mg TPM treatment and TPM+FA treatment significantly reduced NSE levels from 35.71 +/- 5.97 microg/L of the control group to 27.40+/- 6.40, 24.79 +/- 6.22, 21.47 +/- 6.87 and 22.55 +/- 7.02 microg/L respectively (P <0.05). Neuronal apoptosis in the CA3 and CA1 regions were alleviated in the four TPM treatment groups compared with positive control. The number of necrotic neurons was progressively reduced with the increased dose of TPM. The 40 mg TPM+FA treatment group showed less necrotic neurons in the CA3 and CA1 regions than the 40 mg TPM alone treatment group.</p><p><b>CONCLUSIONS</b>TPM has protective effects against epilepsy-induced neuronal damage. The effect is dose-dependent. A combination of TPM and FA can produce a synergistic effect.</p>

Relationship between brain-derived neurotrophic factor and birth weight in neonates / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Recent research has shown that brain-derived neurotrophic factor (BDNF) can improve obesity. This study aimed to explore the relationship between BDNF and birth weight by measuring BDNF levels in the umbilical cord blood of neonates.</p><p><b>METHODS</b>Based on birth weight, 51 first-born full-term healthy neonates were classified into 3 groups: small for gestational age (SGA, n=8), appropriate for gestational age (AGA, n=31) and large for gestational age (LGA, n=12). Height and birth weight as well as umbilical concentrations of BDNF, leptin, insulin, total cholesterol and triglyceride were determined.</p><p><b>RESULTS</b>BDNF level in the SGA group (19980.00 +/- 5470.54 pg/mL) was significantly higher than that in the AGA (10598.00 +/- 6295.71 pg/mL) and LGA (7508.57 +/- 3767.81 pg/mL) groups (P <0.05). There was no significant difference in the BDNF level between the AGA and LGA groups. Stepwise regression analysis showed that the value of BDNF was negatively correlated with birth weight and BMI of neonates, but had no correlation with leptin and insulin levels. Leptin levels showed positive correlations with birth weight and BMI of neonates. There were no significant differences in total cholesterol and triglyceride levels among the three groups.</p><p><b>CONCLUSIONS</b>BDNF is closely correlated to birth weight but not correlated with leptin and insulin in neonates.</p>

An experimental study on hepatotoxicity of topiramate in young rats / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Topiramate (TPM) has an evident efficacy in the treatment of childhood epilepsy for multiple pharmacologic properties. However it was reported that it may cause adverse effects such as liver failure and hepatitis, which arouses the attention of the medical field. This study aimed to investigate the hepatotoxicity of low-dosage, high-dosage TPM or TPM along with valproate sodium (VPA) in aspects of biochemistry indexes, oxidative stress indexes and liver pathomorphology in young rats.</p><p><b>METHODS</b>Sixty 3-week-old male Wistar rats were randomly assigned into five groups of 12 rats (Groups A-E). The rats in the experimental groups (Groups A-C) were administered intragastrically with TPM 40 mg/(kg.d), 80 mg/(kg.d) and TPM 40 mg/(kg.d) plus VPA 300 mg/(kg.d) respectively. The rats in the negative control group (Group D) were administered with the same volume of distilled water. The ones in the positive control group (Group E) were treated by injection of 10% carbon tetrachloride dissolved in olive oil subcutaneously at a dose of 5 mL/kg twice a week. After 3-month administration, the changes of body weight and liver pathomorphology were observed; biochemical markers in serum and indexes of oxidative stress in liver homogenate associated with hepatotoxicity were examined.</p><p><b>RESULTS</b>The body weights of rats in the experimental groups were significantly lower than that of rats in the negative control group. The levels of serum alanine aminotransferase, alkaline phosphatase and the content of malondialdehyde, and the activity of superoxide dismutase in liver tissues did not change significantly in the experimental groups. The contents of glutathion in the high dosage of TPM group (29.85 +/- 1.62 mg/g prot) or in the TPM plus VPA group (29.63 +/- 4.47 mg/g prot) were significantly reduced compared with those of the negative control group (33.09 +/- 1.69 mg/g prot) and that of the low dosage of TPM group (32.43 +/- 2.11 mg/g prot) (both P < 0.05). In the histopathological examination, extensive steatosis and diffuse punctate necrosis of hepatocytes distributed in the portal area were found by microscopy in the positive control group. There were granular degeneration of some hepatocytes near the central veins of hepatic lobules in the low dosage of TPM group and punctate necrosis of some hepatocytes in the high dosage of TPM group. In the TPM plus VPA group, histological examination showed granular degeneration and fatty degeneration of partial liver cells and punctate necrosis of some hepatocytes.</p><p><b>CONCLUSIONS</b>Long-term use of TPM can decrease antioxidant capacity of organism, resulting in slight pathological changes of liver tissues. High dosage of TPM or TPM along with VPA administration enhances the risk of the side effects.</p>

Treatment of hemolytic uremic syndrome after acute stage / 中华儿科杂志

<p><b>OBJECTIVE</b>Hemolytic uremic syndrome (HUS) is a common primary disease that can cause acute renal failure in childhood. Renal disease is the most important long-term complication in patients who survived the acute stage of HUS. Use of angiotensin-converting enzyme inhibitors (ACEI) and a restricted protein intake may be beneficial to the patients. However, it is not established whether such patients should be treated with steroids and immunosuppressors. The present study aimed to probe into the benefit of using steroid and immunosuppressor in patients after acute stage of HUS.</p><p><b>METHODS</b>The subjects included 17 patients (aged 9 months to 15 years, 12 males, 5 females) with HUS. Thirteen patients recovered from the acute stage of HUS, and underwent continuative treatment and follow-up. All the patients were treated with ACEI and early restriction of protein intake. Additionally, 2 children manifested as glomerulonephritis, one was treated with triperygium glycosides. Other 11 children who manifested as nephrotic syndrome were treated with prednisone, among them 5 children had no response or had incomplete response to prednisone, for these children short-term high dose cyclophosphamide or methylprednisolone pulse treatment were added; in 3 of the children short-term high dose methylprednisolone treatment was applied additionally for membranoproliferative glomerulonephritis and/or focal segmental glomerulosclerosis and crescentic glomerulonephritis.</p><p><b>RESULTS</b>After follow-up for 2 months to 8 years, 4 patients with milder disease recovered, their blood pressure, renal function and urinalysis became normal, but 1 patient had recurrence. Among 9 patients with severe disease, 6 maintained normal blood pressure, recovered renal function and urinalysis, the other 3 patients failed to comply with treatment protocol and died during the 3rd, 9th and 13th month. The remainder (4 cases) gave up therapy and died on the 27th to 48th days of the course.</p><p><b>CONCLUSION</b>The treatment applied in this study could improve the prognosis of patients after acute phase of HUS evidently by using the steroid and immuno suppressor according to clinical classification and pathological findings. It is recommended that triperygium glycosides is beneficial to children with glomerulonephritis, proteinuria and hematuria after acute stage of HUS. Adjustment of therapeutic schedule based on pathological findings after renal biopsy is helpful. To the patients with progressive renal failure who have no response to the steroid and immunosuppressors, steroid and immunosuppressor should be discontinued and dialysis treatment should be applied. Protocol compliance is also an important factor.</p>

Protective Effect of Topiramate and Folic Acid on Mitochondrial Damage in Hippocampal Neurons during Pentylenetetrazol-Induced Kindling in Immature Rats / 实用儿科临床杂志

Objective To explore protective effect of topiramate (TPM) and folic acid (FA) on mitochondrial damage in hippocampal CA3 neurons during pentylenetetrazol- induced kindling in immature rats.Methods Pentylenetetrazol (PTZ) - induced kindling in rats was used to establish rat models of epilepsy.Forty-eight 3-week-old male Wistar rats were randomly divided into 4 groups: two therapy groups with TPM 40 mg/(kg?d) or TPM 40 mg/(kg?d) and FA 5 mg/(kg?d) administration, 2 control groups (positive control group and negative control group) with the equal amount of distilled water administration. The seizure behaviors of rats were evaluated. Two months later, the rats were killed and the brain sections were made. The mitochondrial ultrastructures of neurons in hippocampal CA3 region were observed with transmission electron microscope.Results In the positive control group, the frequency of seizure was (48.4 ? 3.7)times, while in TPM group (44.3 ? 3.1)times and in TPM and FA group(40.8 ? 3 .7)times.The differences were significant among three groups (Pa

Effect of glutamine on small intestinal repair in weanling rats after chronic diarrhea / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the nutrient effect of glutamine on small intestinal repair in weanling rats after chronic diarrhea.</p><p><b>METHODS</b>Forty 21-day-old wistar rats were randomly divided into five groups (8 in each). Animal model of chronic diarrhea was induced by a lactose enriched diet in the weanling Wistar rat, normal control group was fed with a standard semipurified diet, and after 14 days the rats in both groups were killed to test the establishment of the model. After the establishment of the model, the other groups were fed with the standard semipurified diet to recover for 7 days, and were randomly divided into three groups: non-intervention group, glutamine (Gln)-intervention group and control group. Glutamine concentrations in blood was detected by high-performance liquid chromatography (HPLC). Morphological changes including villus height and villus surface area of the jejunum were measured under a light microscope and electron microscope, expression of proliferating cell nuclear antigen (PCNA) as an index of cell proliferation was observed using immunohistochemical staining and image analysis.</p><p><b>RESULTS</b>The diarrhea rate in model group was 100 percent, average diarrhea index was 1.16 +/- 0.06, but both diarrhea rate and average diarrhea index in control group were 0 (P < 0.01), which affirmed establishment of the model. There was significant decrease of body weight, plasma Gln concentration, villus height, villus surface area and expression of PCNA in non-intervened group compared with the control group (P < 0.01). There was still significant decrease of body weight, villus height and villus surface area in Gln-intervened group compared with control group (P < 0.01), but plasma Gln concentration and expression of PCNA in Gln-intervened group had recovered to normal (P > 0.05). And compared with non-intervened group, except for body weight (P > 0.05), plasma glutamine, villus height, villus surface area and expression of PCNA were all significantly increased in Gln-intervened group.</p><p><b>CONCLUSION</b>Chronic diarrhea can induce malnutrition and reduce the villus height, villus surface area, expression of PCNA and plasm glutamine concentration. Oral glutamine could improve the proliferation of crypt cell and promote repair of intestinal mucosa after chronic diarrhea.</p>

Renal transplantation in children, report of 21 cases / 中华儿科杂志

<p><b>OBJECTIVE</b>The survival rate of cadaveric renal transplant in children has been improved following the development of transplantation technology and the application of immunosuppressive agents. In this study, the prognosis of renal transplantation, operative procedure and immunosuppressive agents administration in 21 children with end-stage renal disease (ESRD) were analyzed.</p><p><b>METHODS</b>From January 1985 to December 2001, 21 patients (9 males and 12 females with a mean age of 14 +/- 2 yr, mean body weight of 33.4 kg and mean height of 136.5 cm) received renal transplantation because of ESRD were enrolled in the study. The patients with an average GFR of 8.28 ml/min were managed with dialysis for 13.4 months in average pro-transplantation. All cadaveric kidneys were from adults, which included 1 donor with one HLA mismatch, 3 with two mismatches, 5 with three mismatches and 4 with four mismatches. All transplantations were performed with anastomoses of the adults' renal artery and vein to the children's iliac externa artery and iliac externa vein. Biological inducement therapy was given in 4 cases. At the first 3 - 5 days post-transplantation, methylprednisolone was administered [7 mg/(kg.d)]. All patients received baseline diploid or triple immunosuppression therapy of cyclosporin A [6 - 8 mg/(kg.d)] or FK506 [0.18 - 0.25 mg/(kg.d)], mycophenolate mofetil [MMF 10 - 15 mg/(kg.d)] or azathioprine [1 - 3 mg/(kg.d)] and prednisone [0.4 - 0.6 mg/(kg.d)]. High-dose methylprednisolone [10 mg/(kg.d)] was administered to control the acute rejection.</p><p><b>RESULTS</b>The renal function of patients was restored 5.6 days in average after transplantations. The 1st, 3rd and 5th year survival rates of recipient/graft were 95.2%/95.2%, 86.7%/73.3% and 72.7%/63.6%, respectively. One case had super-acute renal rejection, 5 cases had acute rejection, 3 cases had delayed graft function and 3 patients died. The longest survival time was 12 years. The major complications included hypertension (47.6%), diabetes (19.4%), infection (19.4%) and drug-induced hepatic injury (14.2%). Catch-up growth was seen in most of the pediatric recipients.</p><p><b>CONCLUSION</b>Renal transplantation is the most ideal method to treat children with ESRD, and the growth of the pediatric patients will be improved after transplantation. Adult donor kidneys adapt to the school age patient. And the protocol of immunosuppressive therapy (prednisone plus MMF and FK506) should be applied.</p>