OBJECTIVE: The precise mechanism of glucocorticoid-induced apoptosis has not yet been elucidated. Survivin, a member of the inhibitors of apoptosis protein family, correlates with inhibition of apoptosis, proliferation, angiogenesis and multiple drugs resistance. This study aimed to investigate the variation of the survivin gene expression in apoptosis induced by dexamethasone (Dex) in the human T-lineage acute lymphoblastic leukemia (ALL) cell line, CEM-WT cells. METHODS: The logarithmically growing CEM cells cultured in vitro (cell density 2×105/mL) were exposed to 0.1, 0.5, 1, 5, and 10 μM Dex, then were collected 24, 48 and 72 hrs later. Untreated CEM cells were used as Controls. The cell viability was determined by trypan blue dye exclusion. Apoptosis was evaluated by morphology and flow cytometry. Survivin protein and gene were analyzed by Western Blot and RT-PCR. RESULTS: CEM cells growth was obviously inhibited by 0.1, 0.5, 1, 5, and 10 μM Dex from 48 hrs. The inhibition effect was dose-and time-dependent. CEM cells treated with Dex (≥5 μM) exhibited typical apoptotic features. The apoptosis increased after 5 μM Dex treatment in a time-dependent manner, with the apoptosis percentage increasing from 14.9% (12 hrs) to 46.2% (48 hrs). Compared with that of the Control group, the expression of survivin protein was down-regulated, with the expression rate of 54.6%, 45.5%, 15.8% and 9.7% respectively at 12, 24, 48 and 72 hrs after 5 μM Dex treatment. 5 μM Dex treatment also resulted in a decrease of survivin mRNA expression. The survivin mRNA expression was 76.4%, 67.3%, 55.0%, 49.9%, 38.3% and 18.3% of the Control respectively at 6, 12, 24, 48 and 72 hrs after Dex treatment. CONCLUSONS: Apoptosis induced by Dex in CEM cells is associated with downregulation of the survivin expression.
OBJECTIVE: Overseas research has shown the value of brain natriuretic peptide (BNP) in the diagnosis and treatment of heart failure in children. However, a reference range of BNP values is lacking, limiting its clinical application. This study was designed to determine a reference range for children aged 1 to 16 years. METHODS: Plasma BNP (BNP32, NT-proBNP) concentrations were measured in 190 healthy children (95 boys and 95 girls) using an enzyme immunoassay. Their age ranged from 1 to 16 years (mean=10.6±4.2 years). RESULTS: The mean plasma concentration of BNP32 in 190 children was 51.89±48.36 pg/mL, with the 10th and the 90th percentile rank of 27.00 pg/mL and 75.00 pg/mL respectively. The mean plasma concentration of BNP32 in girls was 60.33±62.91 pg/mL, and 44.22± 27.14 pg/mL in boys, but no statistical differences were found. The mean plasma concentration of NT-proBNP in 190 children was 246.04±67.27 fmol/mL. The girls had slightly higher plasma NT-proBNP levels than the boys, but there were no statistical differences between them. Neither plasma BNP32 concentration nor NT-proBNP concentration was related to age. CONCLUSIONS: This study first reported a reference range of BNP values for healthy Chinese children aged 1-16 years. Both age and gender are not related to BNP values.
Mucopolysaccharidosis type I (MPS-I) is an inborn error of metabolism with progressive multisystem involvement. Hurler syndrome is the most severe form of MPS-I that causes progressive deterioration of the central nervous system with ensuing death. This study reported the therapeutic effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on Hurler syndrome in one case. The patient was a 25-month-old boy. He underwent allo-HSCT. The donor was his elder sister whose HLA-B locus was not matching. The reduced-intensity of BuCy conditioning regimen in allo-HSCT for this patient was as follows: busulfan 3.7 mg/kg daily at 9 to 6 days before transplantation, cyclophosphamide 42.8 mg/kg daily at 5 to 2 days before transplantation, and rabbit antithymocyte globulin 3.5 mg/kg daily at 1, 3, 5, and 7 days before transplantation. Human granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (CD34+ cells 12.8×106/kg ) were infused and cyclosporine (CSA), short-course methotrexate, daclizumab and mycophenolate mofetil (MMF) were administered to prevent graft-versus-host reaction disease (GVHD). Complete donor-type engraftment was confirmed by Short Tandem Repeat-Polymerase Chain Reaction (STR-PCR) on day 14 after transplantation. Neutrophil and platelet engraftment occurred on days 11 and 19 after transplantation respectively. Only grade I regimen-related toxicity of live and gastrointestinal tract occurred. GVHD and graft failure were not observed. After transplantation, the clinical symptoms and the neurocognitive function were greatly improved in this patient. It was concluded that allo-HSCT was effective for the treatment of MPS-I. The reduced-intensity conditioning regimen was helpful to decrease the regimen-related toxicity. Sufficient immunosuppressive therapy and adequate hematopoietic stem cells infusion may be beneficial to the donor cell engraftment and reducing the incidence of graft failure and GVHD.
OBJECTIVE: To investigate the renal function in newborns with birth asphyxia or intrauterine distress in the first week of life. METHODS: Sixty full-term newborns born between June 2002 and February 2003 were assigned into three groups: Control group (healthy newborns), Intrauterine distress group (Apgar score > 7), and Birth asphyxia group without intrauterine distress (12 mild asphyxia and 8 severe asphyxia) (n=20 each). Urinary levels of α_1-microglobulin (α_ 1 -MG), β_ 2 -microglobulin (β_ 2 -MG) and albumin (Alb) were detected by radioimmunoassay at 0-2, 3-4 and 6-7 days after birth. RESULTS: The urinary levels of α_1-MG, β_2-MG and Alb in the Asphyxia group were significantly higher than those in the Control group at all time points (P<0.05), peaking at 3-4 days after birth. Statistically significant differences were found between the severely and mildly asphyxiated newborns for the urinary levels of α_ 1 -MG, β_ 2 -MG and Alb at all time points (P<0.05). There were no significant differences in the urinary levels of α_ 1 -MG, β_ 2 -MG and Alb between the Intrauterine distress and the Control groups at each time point. CONCLUSIONS: Birth asphyxia may lead to renal glomerular and tubular impairments and it is speculated that the most serious impairment occurs at the 3rd and 4th days of life. The severity of renal impairments is associated with the degree of asphyxia. The renal function of the newborn appears to be normal following intrauterine distress.
OBJECTIVE: Many studies have demonstrated that low levels of insulin-like growth factor-I (IGF-I) may be associated with the hypoxic-ischemic brain damage (HIBD) and that IGF-I has a neuroprotective effect. The role of IGF-II, a structurally and functurally homologous polypepties with IGF-I, is unclear in HIBD. This study was designed to observe the changes of serum and cerebrospinal fluid (CSF) IGF-II levels in neonates with hypoxic-ischemic encephalopathy (HIE) and to investigate its effects on HIE. METHODS: Serum and CSF IGF-II levels in 41 neonates with HIE were measured by radioimmunoassay in the acute phase (postnatal age 12-24 hrs) and the convalescence phase (postnatal age 10-12 days). The 41 HIE neonates included 10 cases of mild, 12 moderate, and 19 severe HIE. Serum samples of 10 normal neonates were used as controls. RESULTS: In the acute phase, serum IGF-II levels in the Mild HIE group (203.28±40.09 ng/mL) and the Moderate HIE group (192.33±39.66 ng/mL) were not significantly reduced, but were obviously reduced in the Severe HIE group (116.72±39.50 ng/mL) compared with normal controls (229.38±43.39 ng/mL) (P<0.01). During the convalescence phase, serum IGF-II levels in the Mild HIE group (285.53± 49.44 ng/mL ) and in the Moderate HIE group (278.69±51.34 ng/mL) increased significantly (P<0.01); CSF IGF-II levels increased in the Mild HIE group from 27.23±7.82 ng/mL (acute phase) to 81.58±9.77 ng/mL (convalescence phase) (P<0.01) and also increased in the Moderate HIE group from 23.43±7.79 ng/mL (acute phase) to 78.48±10.44 ng/mL (convalescence phase) (P<0.01). The patients from the severe HIE group whose neurological symptoms or signs were improved in the convalescence showed higher serum and CSF IGF-II levels than in the acute phase (254.08±48.50 ng/mL vs 122.21±46.26 ng/mL; 69.42±10.20 ng/mL vs 15.05±7.03 ng/mL; P<0.01 ). A positive correlation was found between the serum and CSF IGF-II levels in the HIE group (r=0.69, P<0.01 ). CONCLUSIONS: IGF-II levels in serum and CSF are associated with the pathogenesis and the prognosis of neonatal HIE.
OBJECTIVE: This study examined the changes of regional cerebral oxygen saturation (rSO_ 2 ) by noninvasive near infrared spectrophotometry in neonates with meconium aspiration syndrome (MAS). METHODS: Seventy-three full neonates with MAS were divided into three groups by respiratory symptoms: asymptomatic group (group 1, n=38), common group (group 2, n=28) and severe group (group 3, n=7). Near infrared spectrophotometry was used to measure the cerebral rSO_ 2 on days 1, 3, 5 and 7 after birth. Thirty healthy full-term newborns served as the Control group. RESULTS: The cerebral rSO_ 2 of group 1 decreased significantly compared with that of the Control group between days 1 and 3 (P<0.05). The cerebral rSO_ 2 of group 2 or group 3 was significantly lower than that of group 1 and the Control group on days 1, 3 and 5 (P<0.05). The MAS patients with mild hypoxic-ischemic encephalopathy (HIE) had significantly higher brain rSO_ 2 levels than those with medium or severe HIE on days 2, 3 and 5 (P<0.05). CONCLUSIONS: The cerebral rSO_ 2 decreased in neonates with MAS. The values for rSO_ 2 correlate with the severity of HIE in MAS patients.
OBJECTIVE: To investigate the role of cerebral computed tomography (CT) in the evaluation of the severity of brain injury following hypoxia in neonates. METHODS: A total of 114 full-term newborns who had perinatal hypoxia, including 25 cases of hyoxic-ischemic encephaloathy (HIE), 36 cases of neonatal asphyxia and 53 cases of simple intrauterine fetal distress, were enrolled in this study. Twenty normal newborns served as the Control group. All had cerebral CT scan at 2-7 days of age. Neonatal behavior neurological assessment (NBNA) was performed at 5 days of age. RESULTS: The average NBNA scores were significantly lower and the abnormality rate of NBNA was significantly higher in the HIE group than in the other three groups (P<0.05). The Asphyxia and the Distress groups had also lower NBNA scores and higher abnormality rate of NBNA than the Control group (P<0.05). Twenty-two patients were found to have cerebral CT abnormality in the HIE group, but there was only 1 case in the Control group (P<0.01). The abnormality rate of cerebral CT in the Asphyxia and the Distress groups was not statistically different from that of the Control group. Twenty-five cases of HIE were divided into mild (n=15), medium (n=6) and severe (n=4) by clinical grading but were divided into normal (n=3), mild (n=10), medium (n=7) and severe (n=5) by CT grading. CT and clinical grading on HIE was not consistent. The sensitivity of CT in the diagnosis of mild, moderate and severe HIE was 47%, 33% and 50% respectively, the specificity was 70%, 74% and 86% respectively and the accuracy was 48%, 64% and 80% respectively. CONCLUSIONS: CT evaluation on mild brain injury induced by asphyxia or intrauterine fetal distress is not of any value and the role of CT evaluation on the HIE grade is uncertain and doubtful.
OBJECTIVE: This study investigated the serum levels of interleukin-5 (IL-5), leukotriene B_4 (LTB_4) and C-reactive protein (CRP) in children with Henoch-Schonlein purpura (HSP) at different phases to explore the role of IL-5 , LTB_4 and CRP in the pathogenesis of HSP. METHODS: Serum levels of IL-5, LTB_4 and CRP in 27 normal children and 31 children with HSP at the acute phase and the early recovery phase were detected using ELISA. RESULTS: The serum levels of IL-5, LTB_4 and CRP in children with HSP were 53.8±4.2 pg/mL, 95.3±12.0 pg/mL and 36.10± 11.78 mg/L , respectively at the acute phase. The values were significantly decreased at the early recovery phase (37.8± 3.9 pg/mL , 45.7±10.1 pg/mL, 18.35±6.43 mg/L; P<0.01), but remained higher than those in normal controls (12.7± 3.2 pg/mL , 17.6±5.7 pg/mL, 4.75±2.85 mg/L; P<0.01). The serum levels of IL-5 and LTB_4 positively correlated to the CRP level. CONCLUSIONS: The serum levels of IL-5 and LTB_4 in children with HSP increased during the acute phase and decreased at the early recovery phase, suggesting that IL-5 and LTB_4 may be involved in the pathogenesis of HSP.
OBJECTIVE: Some research has shown that B-type brain natriuretic peptide (BNF) is helpful in differentiating cardiac from pulmonary etiologies of dyspnea in adults. This study was designed to investigate whether BNP concentration could be similarly applied in children presenting with dyspnea. METHODS: Blood samples were collected from 65 children presenting with dyspnea, due to congestive heart failure (CHF, n=24), pneumonia (n=23) or pneumonia together with CHF (n=18). The samples from 15 healthy children were used as the controls. There were no significant differences in age among the four groups. Serum BNP levels were measured using ELISA. RESULTS: Serum BNP levels in the CHF group (141.55±75.99 pg/mL) were significantly higher than those in the Pneumonia group (26.00± 14.57 pg/mL ; P<0.01), and the Pneumonia together with CHF group (113.73±87.05 pg/mL; P<0.05), as well as the Control group (19.31±10.30 pg/mL; P<0.01). The patients with pneumonia together with CHF had significantly higher serum BNP levels than those of the Pneumonia and the Control groups (P<0.01). There were no significant differences in BNP levels between the Pneumonia and the Control groups. The area under the receive operator characteristic (ROC) curve, which demonstrated the diagnostic utility of BNP in differentiating CHF from pneumonia, was 0.978 ( P<0.01 ). At a cut-off of 49 pg/mL, BNP had a sensitivity of 87.5% and a specificity of 95.8% for differentiating CHF from pneumonia. In the 18 patients who were diagnosed with pneumonia together with CHF, 11 had BNP levels above 49 pg/mL . The mean levels of BNP of the 11 patients were significantly higher than those of the patients with pneumonia (172.08± 56.47 pg/mL vs 25.00±14.57 pg/mL; P<0.01) but were significantly decreased after treatment (26.12±15.71 pg/mL; P<0.01 ). CONCLUSIONS: BNP level is of value in differentiating cardiac from pulmonary causes of dyspnea in children. BNP level is also helpful in assessing whether or not severe pneumonia couples with heart failure in children.
OBJECTIVE: This study was designed to investigate the prevalence, clinical characteristics and outcome of upper respiratory infection (URI) caused by Mycoplasma pneumoniae (MP) in children. METHODS: Pharyngeal cultures for MP antibody were performed in 960 children with acute URI. The samples were randomly collected from the outpatient room or emergency room (Observed group). Of the Observed group, there were 232 cases under 1 year of age, and the remainder, were between 1-12 years old. The samples from 100 healthy children aged from 6 months to 12 years were used as the Control group. The prevalence of MP infection between the two groups was compared. The clinical manifestations and the outcome between the patients with MP positive and negative were compared. RESULTS: MP antibody was positive in 31.7% (304/960) of the Observed group but only 9.0% (9/100) in the Control group (P<0.05). The URI patients under 1 year of age had a lower positive rate of MP than those over 1 year old (P<0.05). Coughs and tonsillitis were more common (P<0.05) , but catarrh, gastroenteritic symptoms, herpes, and tetter were rare (P<0.01) in URI patients with MP positive compared with those with MP negative. Pneumonia developed in 14.8% of the patients with MP positive but only 7.0% in those with MP negative (P<0.01). CONCLUSIONS: MP is one of the main pathogens of acute URI in children. Acute pharyngotonsillitis symptoms are predominately presented in children with MP infection. MP infection was commonly seen in children over 1 year old and they are prone to develop pneumonia.
OBJECTIVE: Immunovasculitis is a pathologic process of Kawasaki disease (KD) in the early stage and it is more likely to be resulted from abnormal immunoactivation. It is thus speculated that the serum levels of some cytokines have changed before immunovasculitis occurs, suggesting the cytokines may be useful markers for the early diagnosis of KD. In this study, we measured the serum levels of soluble interleukin-2 receptors (sIL-2R), interleukin-6 (IL-6) and high-sensitive C-reactive protein (hs-CRP) in patients with KD to evaluate the significance of these cytokines in the early diagnosis of KD. METHODS: Serum levels of sIL-2R and IL-6 were measured by rapid one-step sandwich enzyme immunoassay and the serum hs-CRP level was measured by Dade Behring BN ProSpec in 32 KD patients before and after intravenous immunoglobulin (IVIG) therapy. Twenty healthy children were used as the controls. RESULTS: Before IVIG therapy serum levels of sIL-2R (9253.41±2568.38 pg/mL vs 2161.53±696.92 pg/mL; P<0.05), IL-6 (57.19±45.78 ng/mL vs 7.04±1.69 ng/mL; P<0.05) and hs-CRP (117.69 ±42.05 mg/L vs 1.15±0.54 mg/L; P<0.05) in KD patients were significantly higher than those in healthy controls. After IVIG therapy in KD patients serum IL-6 levels returned to normal and sIL-2R and hs-CRP levels decreased significantly but remained significantly higher than controls( P<0.05 ). There was a positive correlation between sIL-2R and hs-CRP levels (r=0.60, P<0.01). IL-6 levels positively correlated with hs-CRP levels in KD patients before IVIG therapy (r=0.68, P<0.01). CONCLUSIONS: sIL-2R, IL-6 and hs-CRP are activated in the development of KD, and they may be of important value in the early diagnosis of KD.
Cerebral venous sinus thrombosis (CVST) rarely occurs in children but has a mortality rate as high as 20%-78%. Because the clinical manifestation of this disease has no specificity it is easy to be misdiagnosed. This paper reported a case of CVST and reviewed the relevant literatures regarding to the pathogenesis, clinical and pathological features, diagnosis and treatment. The patient (male, 8 months old) was referred to the Beijing Children's Hospital with paroxysm headache and after vomiting for 50 days and having double visions for 2 days. He was definitely diagnosed with CVST by magnetic resonance imaging (MRI) and magnetic resonance venography (MRV). His neurological symptoms were improved after receiving intravenous urokinase and hormonal therapy for three weeks followed by oral anticoagulation. It is concluded that headache and papilledema are the most frequent symptoms in CVST and that MRI and MRV may be primal methods for the diagnosis of CVST.
OBJECTIVE: The application and therapeutic effect of hyperbaric oxygen (HBO) in hypoxic-ischemic brain damage (HIBD) remains controversial. Previous studies have focused on the early pathological and biochemical outcomes and there is a lack of long-term functional evaluation. This study was designed to evaluate the long-term pathological and behavioral changes of early HBO therapy on neonatal rats with HIBD. METHODS: Postnatal 7 days (PD7) rat pups were randomly assigned into Control (n=18), HIBD (n=17) and HBO treatment groups (n=17). HIBD was induced by ligating the left common carotid, followed by 2 hrs hypoxia exposure in the HIBD and HBO treatment groups. The Control group was sham-operated and was not subjected to hypoxia exposure. The HBO therapy with 2 atmosphere absolutes began 0.5-1 hr after HIBD in the HIBD treatment group, once daily for 2 days. The spatial learning and memory ability were evaluated by the Morris water maze test at PD37 to PD41. The morphological and histological changes of the brain, including brain weight, survival neurons, AchE positive unit and NOS positive neurons in hippocampal CA1 region, were detected at PD42. RESULTS: The rats in the HIBD group displayed significant morphological and histological deficits, as well as severe spatial learning and memory disability. In the Morris water maze test, the mean escape latency were longer (56.35±22.37 s vs 23.07±16.28 s; P<0.05) and the probe time and probe length were shorter in the HIBD group (29.29±6.06 s vs 51.21±4.59 s and 548±92 cm vs 989±101 cm; both P<0.05) compared with the Control group. The left brain weight in the HIBD group was lighter than that in the Control group (0.601±0.59 g vs 0.984±0.18 g; P<0.05 ). The survival neurons in the hippocampal CA1 region were less (100±27/mm vs 183±8/mm; P<0.05), as well as the AchE-positive unit and NOS-positive neurons (18.50±2.24% vs 27.50±2.18% and 19.25±4.33 vs 33.75±5.57 respectively; P<0.05) after HIBD. Early HBO treatment improved the abilities of spatial learning and alleviated the morphological and histological damage. The mean escape latency (39.17±21.20 s) was shortened, the probe time (36.84±4.36 s) and the probe length (686±76 cm) were longer, and the brain weight (0.768±0.85 g), the survival neurons (133±25/mm) and the AchE-positive unit (21.94±2.73%) increased significantly compared with those of the HIBD group (P<0.05). CONCLUSIONS: Early HBO treatment resulted in a protective effect against HIBD-induced long-term brain morphological and histological deficits and spatial learning and memory disability.
OBJECTIVE: Previous research suggests that dexamethasone (Dex) pretreatment protects neonatal rats against hypoxic-ischemic brain damage (HIBD). Some of the pharmacological effects of baicalin (a traditional Chinese medicine extracted from Scutellaria baicalensis Georgi) are similar to Dex. This study was designed to explore the effect of baicalin on the neuronal apoptosis following HIBD in neonatal rats. METHODS: Six-day-old Sprague-Dawley rats were randomly assigned into Control (without HI), HIBD, Dex-pretreatment and post-treatment, Baicalin-pretreatment and-post-treatment groups. HIBD was induced by ligating the left common carotid artery, followed by exposure to hypoxia. In the pretreatment groups either baicalin (16 mg/kg) or Dex (0.1 mg/kg) was administered to the rats 24 hrs before HIBD; in the post-treatment groups baicalin or Dex was given 30 minutes after HIBD. The rat pups were sacrificed on postnatal day 10, and brain tissues were harvested. Brain water content was determined, morphological changes were observed under a light microscope, and neuronal apoptosis was measured by terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labeling (TUNEL) staining. RESULTS: The brain water content and the number of apoptotic cells were significantly higher in the HIBD group than those of the Control group (P<0.05). Both baicalin and Dex pretreatment decreased the brain water content from 88.9±1.7 % (HIBD group) to 87.4±0.7% (baicalin) or 87.3±0.6% (Dex) (P<0.05) and the number of apoptotic cells were reduced from 251 ± 28 (HIBD group) to 102 ± 47 (baicalin) or 75 ± 26 (Dex) (P<0.05). Baicalin and Dex post-treatment had no effects on the brain water content and the number of apoptotic cells. Loss and degeneration of neurons could be observed in the HIBD group. Baicalin and Dex pretreatment significantly alleviated neuronal injury, but post-treatment did not. CONCLUSIONS: Pretreatment with baicalin, as with Dex, has a protective effect against HIBD in neonatal rats, but baicalin or Dex post-treatment do not reverse the neuronal injuries.
OBJECTIVE: To investigate the protective effects of 15-methy-lipoxin A_4 (LXA_4 ) on mesangioproliferative nephritis in rats and the possible mechanisms. METHODS: Mesangioproliferative nephritis was induced by a single intravenous injection of the mouse monoclonal anti-Thy1.1 antibodies (ER_4) in 20 rats. Ten nephritic rats were injected with 15-methy-LXA_ 4 at 10 minutes before ER_4 antibody injection and then 8-hourly until the rats were sacrificed on day 4 after nephritis induction. The nephritis was evidenced by presence of proteinuria, histologic examination with light microscopy, infiltrating leukocyte assessed by immunofluorescence microscopy, and mesangial cell proliferation assessed by proliferation scoring and by immunohistochemical staining of proliferating cell nuclear antigen (PCNA). Expressions of interleukin (IL)-1β and IL-6 protein or mRNA in glomeruli were determined by radioimmunoassay or RT-PCR, respectively. Phosphorylated phosphoinositide 3-kinase (PI3-K), Akt_1 and p27 kip1 in glomeruli were analyzed by Western Blot. Activities of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT_3) in glomeruli were assessed by electrophroretic mobility shift assay (EMSA). Results: There were increases in glomerular infiltration of leukocyte, expressions of IL-1β and IL-6 protein and mRNA, and activities of NF-κB in nephritic rats between days 1 and 4 after nephritis induction. The enhanced proteinuria, score of mesangial proliferation, glomerular PCNA positive cells, activities of phosphorylated PI3-K, Akt_1 and STAT_3, and reduced p27 kip1 expression were found on day 4 after nephritis induction. 15-methy-LXA_ 4 treatment significantly reduced the proteinuria, glomerular infiltration of leukocyte, expressions of IL-1β and IL-6 protein and mRNA, score of mesangial proliferation, glomerular PCNA positive cells, activities of phosphorylated PI3-K, Akt_1, NF-κB and STAT_3, and increased the p27 kip1 expression. Conclusions: 15-methy-LXA_ 4 can markedly inhibit the proteinuria, glomerular inflammation, and mesangial cell proliferation induced by anti-Thy1.1 antibodies. The inhibition effects are related to PI3-K/Akt_1/p27 kip1 /cyclin pathway, STAT_3 and NF-κB pathway-dependent signal transduction.
OBJECTIVE: Febrile seizure (FS) is the most common type of seizure disorders in children. Recurrent FS can cause hippocampal neurons injury. At the same time heme oxygenase/ carbon monoxide (HO/CO) system and nitric oxide sythase/ nitric oxide (NOS/NO) system were up-regulated and interacted each other. This study examined the effects of the two systems on the apoptosis of hippocampal neurons in rats with recurrent FS. METHODS: FS was induced in rats by exposure to warm water bath (45.2 ℃), once every 2 days, 10 times in all. Sprague-Dawley (SD) rats aged 21 days were randomly assigned into four groups: Control (37 ℃ water bath exposure), FS, FS + ZnPP-Ⅸ (HO inhibitor) and FS+ L-NAME (NOS inhibitor) groups. The apoptosis of hippocampal CA1 neurons was detected by TUNEL. RESULTS: After recurrent FS, the apoptotic cells in the hippocampal CA1 neurons increased by 225% compared with those in the Control group (P<0.01). The apoptotic cells in the FS+ZnPP-Ⅸ group increased by 62% and 425% compared with those in the FS and the Control groups (both P <0.01). The apoptotic cells in the FS+L-NAME group decreased by 38% compared with those in the FS group (P<0.01) and increased by 100% compared with those in the Control group ( P<0.05 ). CONCLUSIONS: onclusions In recurrent FS, exogenous administration of HO inhibitor ZnPP-Ⅸ may induce an increase of apoptotic cells in hippocampal neurons, while NOS inhibitor L-NAME may decrease the apoptotic cells. The results suggest that the HO/CO system might alleviate neuronal damage, while NOS/NO system might augment neuronal damage.
OBJECTIVE: Basic fibral growth factor (bFGF) might have a role in the restoration and regeneration of injured neurons following hypoxic-ischemic brain damage (HIBD), but its mechanism has not been fully elucidated. Nestin is an intermediate filament protein expressed in dividing cells during the early stages of CNS development, but it can be reinduced in adults during regeneration of injured neurons after CNS injury. This study investigated the effect of exogenous bFGF on nestin expression in neonatal rats following hypoxia-ischemia (HI) and to explore the possible mechanism. METHODS: Eighty-four 7-day-old SD rats were randomly assigned into a Sham-operation group, a HIBD group and a bFGF intervention group (n=28 each). HIBD was induced by ligation of the left carotid artery along with 8% oxygen exposure in neonatal rats from the latter two groups. The Sham-operation group was not subjected to HI. The bFGF intervention group received an intraperitoneal injection of bFGF daily (4 000 U/kg). Each group was randomly subdivided into groups sacrificed immediately, at 3, 12 and 24 hrs and 3, 7 and 14 days after HI (n=4). The expression of nestin in the cerebral cortex, hippocampus and extraventricular zone was examined with immunohistochemical staining and image quantitative analysis. RESULTS: Nestin was weakly expressed in the hippocampus and extraventricular zone and not expressed in the cortex in the Sham-operation group. The nestin in the cortex, hippocampus and extraventricular zone was significantly increased after HIBD, peaking at 7 days. bFGF treatment increased the nestin expression in the cortex, hippocampus and extraventricular zone and statistical differences were observed from 1 to 14 days after HI when compared with the untreated HIBD group. CONCLUSIONS: Exgeonous bFGF can up-regulate the nestin expression in neonatal rats following HIBD. The effects of restoration and regeneration of bFGF on injured neurons may be associated with increased nestin expression in neonatal rats.
OBJECTIVE: Trichosanthin (TCS), a ribosome-inactivating protein extracted from the root tuber of Chinese medicinal herb Trichosanthes kirilowii maximowicz, has various pharmacological properties including abortifacient, anti-tumor and anti-virus. This study aimed to evaluate the effects of TCS on infectious brain injury induced by Herpes simplex virus-1 (HSV-1) in mice. METHODS: Ninety mice were randomly assigned into three groups: Normal control group (n=30) , Model group (n=30) and TCS-treated group (n=30). Viral encephalitis was induced by intracranial inoculation of HSV-1 in the latter two groups. The TCS-treated group was injected with TCS 30 minutes before HSV-1 inoculation. The water content of brain tissue was measured at 1, 12, 24 and 48 hrs, and at 4 and 7 days after HSV-1 inoculation. The viral titer of brain tissue and brain histopathological changes were detected at 7 days after HSV-1 inoculation. The neurological deficient scores were determined daily. RESULTS: The water content of brain tissue in the TCS-treated group between 48 hrs and 7 days after HSV-1 inoculation was significantly lower than that in the Model group (P<0.05), although it was significantly higher than that in the Normal control group (P<0.05). The viral titer of brain tissue in the TCS-treated group was markedly lower than that in the Model group (1.16±0.45 vs 2.89±0.44; P<0.05) 7 days after HSV-1 inoculation. The neurological deficient scores of the TCS-treated group after 24 hrs of HSV-1 inoculation were significantly lower than that in the Model group but were higher than those of the Normal control group. TCS treatment resulted in alleviated pathological changes of brain tissue compared with the Model group 7 days after HSV-1 inoculation. CONCLUSIONS: TCS has protective effects against infectious brain injury induced by HSV-1 in mice.
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