OBJECTIVE: Intravenous indomethacin is the conventional treatment for patent ductus arteriosus (PDA) in preterm infants; however its use is associated with various side effects such as oliguria, gastrointestinal bleeding and reduction of cerebral perfusion. Intravenous ibuprofen has recently been used to treat PDA in preterm infants without reducing cerebral blood flow or affecting intestinal or renal hemodynamics. Intravenous forms of indomethacin and ibuprofen are not available in Iran. This study aimed to examine and compare the efficacy and safety of oral ibuprofen and oral indomethacin for the treatment of PDA in preterm infants. METHODS: Thirty-six infants (gestational age less than 34 weeks) who had echocardiographically confirmed PDA were enrolled in this study. The patients were randomly administered with three oral doses of either indomethacin (0.2 mg/kg, at an interval of 24 hrs) or ibuprofen (a first dose of 10 mg/kg, followed at an interval of 24 hrs by two doses of 5 mg/kg each) (n=18 each group). The rate of ductal closure, side effects, complications, and the infants’ clinical course were recorded. RESULTS: The ductus was closed in all of 18 patients (100%) in the ibuprofen group and in 15 (83.3%) patients in the indomethacin group (P> 0.05). There were no significant differences in the levels of serum blood urea nitrogen and creatinine between the two groups before and after treatment. Necrotizing enterocolitis (NEC) occurred in 3 patients in the indomethacin group and none in the ibuprofen group (P< 0.05). The survival rate at 1 month after treatment was 94% (17/18) in both groups. One infant in the ibuprofen group died from sepsis and one in the indomethacin group died as a result of NEC. CONCLUSIONS: Oral ibuprofen is as effective as oral indomethacin for the treatment of PDA in preterm infants. Oral ibuprofen therapy is associated with a lower incidence of NEC.

OBJECTIVE: Two hundred forty cases of childhood gynecomastia were studied retrospectively. There were 13 cases aged 3 to 10 years and 227 cases aged 11 to 15 years. Of the 240 cases of gynecomastia, 160 presented with bilateral breast enlargement, 50, left breast enlargement, and 30, right breast enlargement. The etiology of gynecomastia of the 240 patients included adolescent breast hyperplasia (n=219), drug ingestion (n=2), and secondary causes (n=5). Fourteen patients did not show identifiable causes and were diagnosed as idiopathic gynecomastia. The 8 patients with identifiable causes received specific treatment. After 1-3 months of treatment, the breasts of the patients improved. The 219 cases of adolescent breast hyperplasia and 14 cases of idiopathic gynecomastia were not given any medication. They were followed up regularly. Most of the patients recovered well within a 27-month follow-up.

OBJECTIVE: To understand the clinical characteristics of hypoxic-ischemic encephalopathy (HIE) in full-term infants and to explore the value of magnetic resonance imaging (MRI) for the early prediction of HIE prognosis. METHODS: The medical data, including histories, clinical manifestations, MRI findings and follow-up outcomes, of 348 full-term infants with HIE between January 2001 and December 2005 were retrospectively reviewed. RESULTS: HIE patients (348 cases) accounted for 8.25% of in-patients (4220 cases) over the five years. The etiology of HIE mainly attributed to birth asphyxia (76.2%), consisting of mild asphyxia (59.2%) and severe asphyxia (40.8%). A poor outcome was confirmed in 10.1% of these patients, including 27.3% in severe HIE, 10.0% in moderate HIE and 1.5% in mild HIE cases. All of patients whose MRI showed diffusion intraparenchymal hemorrhages and cerebral infarctions had poor outcomes. Fourteen (87.5%) out of the 16 cases with basal ganglia and thalamic or internal capsule injury and 9 (81.8%) out of the 11 cases with cytotoxic brain edema diagnosed by diffusion weighted imaging had poor outcomes. CONCLUSIONS: HIE is one of common diseases in newborn infants. The etiology of neonatal HIE mainly attributed to birth asphyxia, mild asphyxia accounting for a greater proportion. MRI findings can be helpful for the early prediction of HIE prognosis.

OBJECTIVE: Asthma is considered as a typical psychosomatic disease. This study aimed to investigate the temperament of asthmatic children and risk factors for asthma. METHODS: Temperamental type and dimensionality were investigated by Carry Temperament Scale in 106 children with asthma. Logistic regression analysis was used to study the risk factors for the development of asthma. One hundred and six age and sex-matched normal children served as controls. RESULTS: There were significant differences in the adaptability, mood value and attention persistence of temperament between asthmatic patients and normal controls. Higher proportion of inter-high difficult temperamental type (17.0% vs 5.7%) and lower proportion of easy temperamental type (16.0% vs 29.2%) were found in children with asthma when compared with controls (P< 0.01). Logistic regression analysis showed that the frequency of cold between 3 and 7 years old, allergic history, idiosyncratic physique, parental history of asthma, house decoration and mood value and attention persistence of temperament were risk factors for the development of asthma. CONCLUSIONS: There were differences in the temperamental type and dimensionality between asthmatic children and normal controls. Children with inter-high difficult temperament and suffered from the above risk factors showed a higher risk for developing asthma.

OBJECTIVE: Impulse oscillometry (IOS) is a novel technique for the evaluation of pulmonary function. Soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) are definitive indicators for the severity of asthma. This study aimed to explore the relationship of IOS pulmonary function with sICAM-1 and sVCAM-1, and their values in childhood asthma. METHODS: IOS via Master Screen System for pulmonary function was performed in 40 children with acute asthma and 25 healthy children. Twenty-three of 40 children with acute asthma were re-tested for IOS pulmonary function at remission. sICAM-1 and sVCAM-1 levels were measured in 23 children with acute asthma, 20 asthmatic children at remission and 16 healthy children. RESULTS: The parameters of IOS pulmonary function, R5, R20, R5-R20, X5, Fres and Zrs in children with acute asthma were significantly higher than in asthmatic children at remission and in normal controls (q= 2.91-15.61, P< 0.01 or 0.05). There were significant differences in R5, R5-R20, Fres and Zrs between the asthmatic children at remission and normal controls (q= 3.08- 9.19, P< 0.01 or 0.05). sICAM-1 and sVCAM-1 levels in children with acute asthma were significantly higher than in asthmatic children at remission and in normal controls (q= 6.23-26.15, P< 0.01). The asthmatic children at remission had higher levels of sICAM-1 and sVCAM-1 than the normal controls (q=16.86, 12.46, P< 0.01). R5-R20 positively correlated with sICAM-1 and sVCAM-1 in children with acute asthma (r=0.45, 0.57, P<0.05). CONCLUSIONS: IOS for pulmonary function and sICAM-1 and sVCAM-1 may be used to evaluate the severity and therapeutic effects of childhood asthma. A correlation exists between IOS pulmonary function and sICAM-1 and sVCAM-1.

OBJECTIVE: To establish reference values of peak expiratory flow (PEF) for children in Xinjiang. METHODS: A total of 3520 healthy children (1705 males and 1815 females) aged from 7 to 16 years were enrolled in this study. PEF was measured using MicroPeak Peak Flow Meter. Children's age, sex, height and weight were recorded. Impact factors for PEF were investigated by multiple stepwise regression analysis. RESULTS: PEF values increased with the increase of age, height and weight and correlated significantly with age, height, weight and sex. The regression equation between sex and height and PEF was obtained, i.e, PEF (y)=-342.98+3.94 x Height (x1) + 26.30 x Sex (x2). CONCLUSIONS: PEF values can be calculated according to children's height and sex.

OBJECTIVE: To evaluate the value of Doppler echocardiography in the diagnosis of pulmonary artery hypertension (PAH) and the effect of PAH on left ventricular remodelling and diastolic function using Doppler echocardiography in children with congenital heart disease (CHD). METHODS: Doppler echocardiography was performed on 45 CHD children with PAH (PAH group) and the results were compared with those of 22 CHD children with normal pulmonary artery pressure (control group). RESULTS: Doppler echocardiography showed that the diameter of end-diastolic left ventricular (18.24±1.71 mm vs 16.28±0.52 mm), the diameter of right ventricular (12.23±2.14 mm vs 8.14±0.73 mm), and the pulmonary artery diameter (11.20±1.35 mm vs 7.92±0.21 mm ) increased significantly in the PAH group compared with those in the control group (P< 0.05). The PAH group had higher velocity of tricuspid valve regurgitation (2.56±0.46 m/s) and higher pulmonary artery pressure (40.23±4.56 mmHg) than the control group (P< 0.05). The PAH group had also higher mitral peak A velocity (AV, 94.56±31.45 m/s vs 51.17±26.67 m/s), higher mitral AV velocity-time intergrate (10.89±2.73 s vs 4.94±1.85 s), higher ratio of mitral AV to mitral peak E velocity (EV) (1.79±0.32 vs 0.59±0.19) and higher ratio of mitral velocity-time intergrate of AV/EV (1.61±0.49 vs 0.45±0.21) than the control group. The left ventricular isovolumetric relaxation time (119.86±54.62 s vs 52.31±28.06 s) was prolonged in the PAH group (P< 0.05). In the PAH group, there was a positive correlation between the increased pulmonary artery pressure and the ratio of mitral AV/EV (r=0.4456, P< 0.01). CONCLUSIONS: Doppler echocardiography is not only an important non-invasive diagnostic technique for PAH in children with CHD, but also a tool which can indicate the left ventricular remodelling and diastolic dysfunction induced by PAH. It is useful to evaluate the severity and the prognosis of PAH secondary to CHD.

OBJECTIVE: Severe asphyxia during peripartum may lead to some sequela of the nervous system. Currently the neurologic outcome of asphyxiated neonates is assessed by using imaging techniques such as cranial ultrasound, CT and MRI except for evaluating perinatal abnormal factors and routine physical examinations of nervous system. These assessment approaches are based on the changes of anatomic structures of neonates. Electroencephalography (EEG) can show early abnormal cerebral functions. This study examined the EEG background activity and investigated the parameters associated with the prognostic assessment in full-term neonates with asphyxia. METHODS: A standard EEG was recorded in 49 asphyxiated full-term neonates aged from 24 hrs to 8 days. Of the 49 neonates, 14 had concurrent mild, 5 had moderate and 9 had severe hypoxic-ischemic encephalopathy (HIE). Thirty-one aged-matched full-term neonates without asphyxia severed as the control group. Forty-three of 49 asphyxiated neonates were followed-up for neurological development for 6-12 months. Important parameters associated with neurological prognosis were evaluated by the principle of data statistics. RESULTS: The mean interburst intervals was prolonged, the amplitude of brain electrical activity during all the states were lower, and the incidence of brief burst and sleep-wake cycle disturbance was higher in the asphyxiated group when compared with the control group (P< 0.05). In the follow-up, 4 infants had poor fine motor function and 7 showed retarded psychomotor development in the asphyxiated group. Gestational age, birth weight, amplitude of brain electrical activity, severity of HIE, occurrence of sleep-wake cycle disturbance and imaging abnormality were shown as important parameters for predicting neurological outcomes in asphyxiated neonates. The infants who EEG showed isoelectric tracings or isoelectric tracings accompanied with much abnormal discharge had very poor prognosis. CONCLUSIONS: EEG background pattern is valuable in predicting neurological outcomes for term neonates with asphyxia. EEG in combination with clinic data such as gestational age, birth weight, imaging examination, and severity of HIE may provide an accurate evaluation of neurological outcome.

OBJECTIVE: To determine the therapeutic effectiveness and safety of polyethylene glycol 4000 (forlax) in the treatment of constipation in children over 8 years old. METHODS: This study was designed as a randomized, positive medicine (lactulose) controlled multicenter trial. A total of 216 children with constipation from 8-18 years old from 7 hospitals across China who were matched with a uniform entry criteria were enrolled in this study. The 216 patients were randomized to receive either oral forlax (20 g/d, n=105) or lactulose (15 mL/d, n=111) for 2 weeks. The therapeutic effects, including bowel movement frequency, stool consistency, clinical complete remission rate of constipation and abdominal symptoms, and the safety of forlax and lactulose were evaluated at 1 and 2 weeks of treatment. RESULTS: The median weekly frequency of bowel movement in the forlax group increased by 4 and 5 times respectively after 1 and 2 weeks of treatment, and increased by 3 and 4 times in the lactulose group (P< 0.05). The stool consistency of the two groups was both improved significantly after treatment. The Bristol score of stool consistency of the forlax and lactulose groups were 3.41±1.11 and 3.64±1.33 respectively (P< 0.05) after 1 week of treatment, and were 4.26±0.89 and 3.63±1.33 respectively (P< 0.05) after 2 weeks of treatment. The clinical complete remission rate of constipation in the forlax and lactulose groups was 70% and 40% respectively (P< 0.05) by week 1 of treatment, and that was 72% and 41% respectively (P< 0.05) by week 2 of treatment. Abdominal pain disappeared in 75% of patients in the forlax group but in only 57% in the lactulose group by week 2 of treatment (P< 0.05). No serious adverse events happened and no abnormalities were found in laboratory tests and physical examinations in the two groups after medication. CONCLUSIONS: Forlax is safe and effective in the treatment of constipation in children over 8 years old.

OBJECTIVE: Some research has shown that there may be memory/caution (M/C) defects in children with primary nocturnal enuresis (PNE). This study aimed to investigate whether the defects affect the intelligence level and the intelligence structure in PNE children.METHODS:Intelligence tests were performed by means of Wechsler Young Children Scales of Intelligence (C-WISC) in 40 children with PNE and 40 age-matched normal children. RESULTS: The full intelligence quotient (FIQ), verbal IQ (VIQ) and performances IQ (PIQ) in the PNE group were in a normal range and did not different from the control group. There were significant differences in the scores for digit extent, decipher, knowledge and arithmetics between the PNE and the control groups (P< 0.05). M/C factor in the PNE group was statistically lower than in the control group (93.44±11.27 vs 100.03±11.79; P< 0.05). CONCLUSIONS: The total intelligence level of children with PNE was normal, but the M/C factor in the intelligence structure had some defects, suggesting that PNE may be related to the abnormity of executive function in the frontal lobe.［Chin J Contemp Pediatr, 2007, 9 (5):433-435］

OBJECTIVE: To investigate the clinical phenotypes and hereditary patterns of the generalized epilepsy with febrile seizures plus (GEFS+). METHODS: Detailed family trees were constructed by inquire and physical examinations for the probands of the 15 pedigrees of GEFS+. Some patients received electroencephalography, cranial CT or MRI examination. The seizures and epilepsy syndromes were classified according to the 2001 Seizure International Classification. The clinical data of GEFS+ were reviewed. RESULTS: The 15 families consisted of 196 individuals. Seventy-five individuals were confirmed with epilepsy. The phenotypes of 64 out of the 75 patients with epilepsy conformed to GEFS+. The 64 patients included 38 males and 26 females (1 deceased) and there was no gender difference in the morbility of GEFS+. The age at onset was all in childhood. GEFS+ had a diversity of phenotypes. Febrile seizures (FS) were confirmed in 44 patients, FS and myoclonic seizure in 1, febrile seizures plus (FS+) in 13, FS+ and absence seizure in 2, FS+ and myoclonic seizure in 1, and FS+ and focal seizure in 3. CONCLUSIONS: The heterogeneity of phenotypes and genetics may be the hallmarks of GEFS+. FS and FS+ are common phenotypes while FS+ and absence seizure, FS+ and myoclonic seizure, and FS+ and focal seizure are rare. If one of the parents is affected in a GEFS+ family, the susceptibility of their children to GEFS+ is the same no matter what gender of their children is. It is speculated that the hereditary pattern of GEFS+ conforms to autosomal dominant inheritance.

Glycerol kinase deficiency (GKD), a rare X-linked recessive disorder, is classified into two types: isolated and complex. Complex GKD is an Xp21 contiguous gene deletion involving the glycerol kinase locus together with the adrenal hypoplasia congenita (AHC) or Duchenne muscular dystrophy (DMD) loci or both. Its clinical features depend on the involved loci. GKD can be confirmed by an elevated urinary glycerol concentration tested by gas chromatography mass spectrometry (GC/MS). The three cases reported here were all male, presenting symptoms from neonatal period. The predominant clinical profile was characterized by hypoadrenocorticism, glyceroluria and Duchenne muscular dystrophy. After receiving a low fat diet and glucocorticoid replacement, they improved with relieved symptoms of hypoadrenocorticism. But they had significant developmental delays and myasthenia. In the follow-up two of them died of adrenal crisis.

OBJECTIVE: This study examined the NgR expression in oligodendrocyte precursor cells (OLPs) and its changes after oxygen & glucose deprivation (OGD) in order to explore the role of NgR expression in the regeneration of OLPs after OGD in neonatal rats. METHODS: The OLPs from 2-day-old neonatal rats were separated by improved separation and purification through agitation and then cultured in chemically defined medium. OLPs OGD model was prepared using the medium consisting of Na2S2O4 and Earle's fluid in vitro. Immunofluorescence assay was applied to identify the OLPs with its specific antibodies such as A2B5, O4 and O1. Western blot was used to detect the NgR expression in OLPs 10 and 30 minutes after OGD. The livability rate of cells was detected by MTT. RESULTS: NgR expression was found in both the cell body and the prominence of purified OLPs. NgR expression in OLPs increased significantly 10 and 30 minutes after OGD compared with that in OLPs without OGD (controls, P< 0.05). MTT showed that the livability rate of OLPs at 30 minutes following OGD was significantly lower than that of controls (65.97±3.69% vs 97.17±6.88%, P< 0.05). CONCLUSIONS: NgR is expressed in both the cell body and the prominence of OLPs. NgR expression increases while cell livability decreases following OGD, suggesting that NgR may play a role in the inhibition of regeneration of OLPs.

OBJECTIVE: To investigate the role of connective tissue growth factor (CTGF) in pulmonary fibrosis in rats with hyperoxia-induced chronic lung disease (CLD). METHODS: Eighty premature rats were randomly exposed to hyperxia (FiO2=0.90) or room air (control group) (n=40 each). CLD was induced by hyperoxia exposure. The expression of CTGF mRNA and transforming growth factor-β 1 (TGF-β 1), the levels of type I collagen and the proliferating cell nuclear antigen (PCNA) index were assayed with enzyme linked immunoadsorbent (ELISA), immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) on days 1, 3, 7, 14 and 21 after exposure. RESULTS: There were no differences in the levels of type I collagen, PCNA index, TGF-β 1 protein and CTGF mRNA between the CLD and the control groups within 3 days after exposure. In the CLD group, the expression of TGF-β 1 protein increased on the 7th day, remained at a higher level on the 14th and 21st day after exposure; the higher levels of type I collagen, PCNA index and CTGF mRNA were detected on the 14th day and peaked on the 21st day after exposure when comparing the control group. CTGF mRNA expression was positively correlated with type I collagen levels in the CLD group (r=0.89, P< 0.01). CONCLUSIONS: The expression of CTGF in lung tissues is associated with pulmonary fibrosis in CLD rats.

OBJECTIVE: Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease. It is characterized by selective loss of spinal cord motor neurons leading to muscle atrophy and is the result of mutation or deletion of the survival motor neuron (SMN) gene. Currently, there are no effective therapies for this disease. Stem cell therapy is a new prospect for SMA patients. This study aimed to investigate whether mesenchymal stem cells (MSCs) can be differentiated into neuron-like cells (NLCs) in SMA patients in order to provide a basis for stem cell therapy for SMA. METHODS: SMA was definitively diagnosed using polymerase chain reaction-restriction fragment length polymerphhism (PCR-RFLP). Two children without SMN1 gene deletion were used as controls. MSCs were isolated and purified from SMA patients and controls, and induced into NLCs by bFGF and baicalin. The NLCs were identified by immunofluourescence staining with NSE and NF monoclonal antibodies. RESULTS: SMA patients showed the deletion of SMN1 exon 7. The morphous and proliferative speed of MSCs between SMA patients and controls were similar. After 6-day induction, MSCs of the two groups displayed similar morphology to that of neurons, with long processes forming extensive networks. NSE and NF, the neuronal markers, were detected in the differentiated NLCs of the two groups. CONCLUSIONS: SMN1 deletion appears not to affect the proliferation and differentiation of MSCs. MSCs of SMA patients can be differentiated into NLCs.

OBJECTIVE: Spinal muscular atrophy (SMA) is one of common autosomal recessive diseases and is characterized by degeneration of the anterior horn cells of the spinal cord. The reported prevalence is 1/10000 live births with a carrier rate of one in 50. It is important in genetic counseling to identify the carriers with one copy deletion for the survival motor neuron (SMN1) gene. However, the duplication of the SMA locus makes the detection of SMA carriers difficult. This study aimed to determine the potential of the quantitative PCR analysis in the identification of SMA carriers. METHODS: The SMN1 gene copy number was detected by real-time PCR with TaqMan technology in 109 SMA parents of affected children and 40 normal controls. RESULTS: The average copy numbers of SMN1 in the individuals with known one copy of the SMN1 gene and with the two copies were 0.777±0.035 (CV=4.5%) and 2.064±0.120 (CV= 5.8%) respectively. The average copy number of SMN1 in all of the parents with affected individuals was 0.798±0.108 (CV=13.5%), and that of normal controls was 2.106±0.18 (CV=8.5%). About 98% of SMA patients' parents carried 1 copy SMN1, and 95% of normal controls carried 2 copies. CONCLUSIONS: The gene copy numbers for SMN1 were one and two for SMA carriers and non-carriers, respectively. Our results suggested that the quantitative PCR analysis can distinguish the SMN1 deletion carriers from non-carriers.

OBJECTIVE: To study the expression of signal transducer and activator of transcription 3 (Stat3), hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in Wilms' tumor and their roles in the development of Wilms' tumor. METHODS: The expression of Stat3, HIF-1α and VEGF were detected by the immunohistochemical staining in 52 specimens from Wilms' tumor tissues, 47 from adjacent kidney tissues and 8 from normal kidney tissues. The expression intensity was analyzed by computer image processing. RESULTS:The expression of Stat3, HIF-1 and VEGF were significantly up-regulated in Wilms' tumor tissues compared to those in adjacent tissues and normal kidney tissues (P< 0.05). Stat3 and VEGF proteins in Wilms' tumor tissues of stage III-IV and high risk histopathology were significantly higher than those of stage I-II and low risk histopathology. The higher expression of HIF-1 in Wilms' tumor tissues was shown in tumors with high risk histopathology and tumor size ≥ 6 cm. CONCLUSIONS: Increased expression of Stat3, HIF-1 and VEGF were found in Wilms' tumor tissues, and may be related to the development and angiogenesis of Wilms' tumor. Stat3 may regulate the expression of HIF-1 and VEGF, so it could be an effective target for inhibiting VEGF expression and angiogenesis of Wilms' tumor.

OBJECTIVE: Gap junctions, the clusters of intercellular channels, play an important role in synchronizing electrical activity. This study investigated the effect of gap junction blocker carbenoxolone (CBX) on epileptic activity in pentylenetetrazo (PTZ)-kindled rats. METHODS: Thirty adult male SD rats were randomly divided into three groups: control, PTZ-kindled and CBX-treated groups (n=10 each). The rats from the PTZ-kindled and the CBX-treated groups were intraperitoneally injected with PTZ (35 mg/kg.d) to induce epilepsy. After epilepsy kindling, they were intraperitoneally injected for 3 days with CBX (10 mg/kg) (CBX-treated group) or with normal saline (PTZ-kindled group). The control group received intraperitoneal injections of normal saline. Anti-GFAP, anti-Fos, and anti-NMDARZ immunohistochemical ABC methods were used to detect the expression of GFAP-Li, Fos-Li and NMDAR2-Li in the hippocampus respectively. RESULTS: Spontaneous seizures occurred in PTZ-kindled epileptic rats. CBX administration reduced spontaneous seizures. The NMDAR2-Li and Fos-Li neurons as well as GFAP-Li astrocytes in hippocampi increased in PTZ-kindled epileptic rats compared with controls. The numbers of Fos-Li (93.75±7.94 vs 165.25 ±15.87, P< 0.05) and NMDAR2-Li neurons (61.47±3.62 vs 148.72±14.53, P< 0.01) in the CBX-treated group were significantly less than in the PTZ-kindled group. There were no significant differences in the GFAP-Li expression between the CBX-treated and the PTZ-kindled groups. CONCLUSIONS: CBX may inhibit spontaneous seizures and decrease the numbers of Fos-Li and NMDARZ-Li neurons, thus providing anti-epileptic effects.

OBJECTIVE: To develop a mouse model to mimic the behavioral and neurochemical changes of Tourette syndrome (TS) by 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) induction and to investigate the effects of fluoxetine and haloperidol on head twitch response (HTR) induced by DOI. METHODS: 1) Preparation of mouse model of TS: Forty mice were randomly divided into experimental and control groups (n=20 each). DOI (1 mg/kg) was administered by peritoneal injection in the experimental group. The control group was injected with normal saline. The levels of dopamine (DA) and homovanillic acid (HVA), the metabolite of DA, in both groups were measured by high performance liquid chromatography and electrochemical detection. 2) Effects of fluoxetine and haloperidol on HTR: Eighty mice were randomly administered with either fluoxetine (2 mg/kg), haloperidol (0.8 mg/kg), fluoxetine + haloperidol or normal saline. DOI (1 mg/kg) was peritoneally injected 20 minutes later (acute trial) or 18-20 hrs after a 21 days injection of fluoxetine or haloperidol (chronic trial). The frequency of DOI-induced HTR was observed immediately after DOI injection. RESULTS: The levels of DA and HVA in the experimental group were significantly lower than those in the control group (DA: 45.00±11.24 ng/mg vs 58.16±14.51 ng/mg; HVA:10.54±1.86 ng/mg vs 12.82±2.66 ng/mg). In both acute and chronic trials, the frequency of DOI-induced HTR decreased significantly in mice administered with haloperidol alone or together with fluoxetine (P< 0.05), but it did not change significantly in mice administered with fluoxetine alone compared with the normal saline group.CONCLUSIONS:The levels of DA and HVA are reduced in mice with DOI-induced HTR. DOI-induced mouse mode of HTR can mimic the neurochemical and behavioral changes of TS paritially. Haloperidol can inhibit DOI-induced HTR in mice, but fluoxetine can not.

OBJECTIVE: Recent studies suggest that the disruption of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) functions plays a pivotal role in the pathogenesis of bronchopulmonary dysplasia (BPD). The aim of this study was to investigate the changes of VEGF and eNOS expression in the lungs of premature rats exposed to moderate hyperoxia in order to explore possible relationships with BPD. METHODS: Premature rats delivered by hysterotomy at 21 days gestation were randomly continuously exposed to moderate hyperoxia (60% FiO2) and room air. The rats were sacrificed at 1, 4, 7, 11 and 14 days of exposure (6 rats at each time point). Lung sections were stained with hematoxylin and eosin for histological examination. Expression of VEGF and eNOS proteins and mRNA were assayed using immunohistochemistry and RT-PCR. RESULTS: After 4 days of hyperoxia, lungs developed interstitial fibrosis, abnormal vascular patterns and decreased alveolar septation. These changes became more obvious with more prolonged hyperoxia exposure. The expression of VEGF protein after 4 and 7 days of exposure decreased significantly in the hyperoxia group compared with controls. The expression of VEGF mRNA in the hyperoxia group was also lower after 4 and 7 days of exposure. Both VEGF protein and mRNA levels decreased with increasing hyperoxia exposure time. The expressions of eNOS protein and mRNA also progressively decreased with increasing hyperoxia exposure. CONCLUSIONS: Hyperoxia caused progressive reduction in lung VEGF and eNOS expression as well as abnormalities of lung structures, including decreased vascular growth and impaired alveolarization. These histologic changes are similar to those of BPD. The data support a link between BPD and decreased expression of VEGF and eNOS.

OBJECTIVE: It has been shown that triptolide can attenuate pulmonary arterial hypertension in rats. This study was designed to investigate the therapeutic effect of triptolide on pulmonary hypertension in rats and possible mechanisms. METHODS: Sixty Sprague-Dawley (SD) rats were randomly divided into 6 groups: normal control, model, continuous triptolide-treated, delayed triptolide-treated and two placebo groups for continuous and delayed fashions (n=10 each). The rats from the last 5 groups were injected with monocrotaline (MCT, 60 mg/kg) on day 7 after left pneumonectomy. The rats in the continuous triptolide-treated group received therapy from day 5 to 35 with triptolide (0.25 mg/kg intraperitoneally, every other day) and those in the delayed triptolide-treated received therapy with triptolide (0.20 mg/kg intraperitoneally, daily) from day 21 to 35 after operation. The hemodynamic parameters were detected by catheterization and the pathologic changes of small pulmonary arteries were evaluated by light microscopy 5 weeks post-operation. The expression of matrix metalloproteinases (MMPs) was assessed by immunohistochemistry and quantitative fluorescence PCR of relevant (MMP2 and MMP9) mRNAs. RESULTS: By day 35 after operation, the mean pulmonary arterial pressure (mPAP, 38.10±1.20 vs 16.70±1.16 mmHg), the ratio of right ventricle/left ventricle plus septum [RV/(LV+S), 62.45±5.28% vs 22.76±3.01%] and the vessel obstructive scores (VOS, 1.736±0.080 vs 0.000±0.000) increased significantly in the Model group compared with those of the normal control group (P< 0.01). The expression of MMP2 and MMP9 and their mRNA expression in lung tissues obviously also elevated in the Model group (P< 0.05). The continuous and the delayed triptolide-treated groups had significantly lower mPAP (20.80±1.03 and 26.20±1.03 mmHg, respectively) and less right ventricular hypertrophy and pulmonary arterial neointimal formation compared with the model and the placebo groups. The two treated groups also demonstrated decreased expression of MMP2 and MMP9 and their mRNA expression in lung tissues. There were significant differences in mPAP, RV/(LV+S) and VOS between the two triptolide-treated groups. CONCLUSIONS: Triptolide attenuates the development of pulmonary hypertention and right ventricular hypertrophy and promotes regression of pulmonary arterial neointimal formation in pneumonectomized rats that received MCT, possibly through an inhibition of MMPs activity.