Objective To observe the abnormality on behavioral ability of transgenic mice for HRX-EEN fusion gene.Methods Transgenic mice for HRX-EEN fusion gene(transgenic group,n=12)and C57/BL mice(control group,n=12)were tested in hidden platform training(day 1 to day 4)and probe trial testing(day 5)in Morris water maze in which ability of spatial learning and retention was assessed.Results In hidden platform training,the latencies of transgenic group were longer than those in control group,and significant differences were observed between the two groups for day 2,3 and 4(P

OBJECTIVETo study the inhibition of berberine (BBR) against ECV-304 apoptosis induced by Staphylococcus aureus (S. aureus).

METHODSECV-304 cells were pre-treated with 128 microg/mL BBR for 2 h and then S. aureus was added (1:100). The viability of cells was detected by MTT (3-4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The morphological changes were observed by Hoechst 33258 staining. The protection of BBR for infected cells was detected by DNA Ladder.

RESULTSECV-304 cells' viability were not obviously affected by berberine. But S. aureus induced ECV-304 cells' viability could be significantly inhibited by pre-treatment of BBR (P < 0.05). Besides S. aureus-induced ECV-304 apoptosis could be reduced, with significantly lessened apoptotic body and unobvious DNA degradation.

CONCLUSIONBBR could significantly inhibit S. aureus induced ECV-304 apoptosis.

Apoptosis ; drug effects ; Berberine ; pharmacology ; Cell Line ; Human Umbilical Vein Endothelial Cells ; drug effects ; microbiology ; pathology ; Humans ; Staphylococcus aureus

Objective To investigate the relationship of folates,vitamin B_(12) with tan phosphorylation and the possible mechanism in Alzhcimer's disease (AD).Method Tau protein phosphorylation was examined in hippocampns of rats of two months old and forty months old treated or untreated by folates and vitamin B_(12) using Western blot and immunohistochemistry with phosphorylation dependent and independent tau antibodies.Results We found that tau phosphorylation in aged rat brain showed a significant higher level than that in the two-month olds.Folates combined with vitamin.B_(12) could decrease tau phosphorylation by 27% at the site of Ser396/404 of hippoeampus in aged rats.Conclusion It suggests folates and vitamin B_(12) may play an important role in preventing the neurodegenerative change via effeeting tau phosphorylation in AD brain.

OBJECTIVEPulmonary hypertension is a proliferative vascular disease characterized by pulmonary vascular structural remodeling. Until now, the pathogenesis of pulmonary hypertension is still not fully understood. Although considerable progress has been made, there is, to date, no cure for advanced pulmonary vascular disease. Recently, a number of studies suggest that endogenous vascular elastase (EVE) play a role in the vascular changes associated with pulmonary hypertension. The purpose of the study was to determine whether an elastase inhibitor might reverse advanced pulmonary vascular disease produced in rats by injection of monocrotaline.

METHODSOne hundred and twenty male Sprague-Dawley rats were used in this study. The rats were divided into three groups: control, model and ZD-0892 groups. In the model and ZD-0892 groups, the rats were subjected to a single subcutaneous injection of monocrotaline (60 mg/kg) in the hind flank, while the rats in control group received an equivalent volume of 0.9% saline. From day 21, the rats in the ZD-0892 and model groups received twice-daily gavage tube feedings of either ZD-0892 at a dose of 240 mg/kg per day or its administration vehicle, while the rats in control group were subjected to an equivalent volume of 0.9% saline. On days 21, 28 and 35 post-injection, the elastolytic activity was measured with a fluorescence microplate reader and pulmonary artery pressure was detected via catheterization. Meanwhile, the lungs were evaluated morphologically, using the barium-gelatin perfusion technique.

RESULTSThe injection of monocrotaline led to severe pulmonary hypertension in rats 21 days later and pulmonary artery elastolytic activity increased remarkably. A 1-week treatment with ZD-0892 resulted in declines in elastase activity. This was associated with significant declines in pulmonary artery pressure, decreases in muscularization of peripheral arteries and reductions in medial hypertrophy. After 2 weeks, elastase activity returned to normal level. Pulmonary artery pressure and structure were normalized.

CONCLUSIONIncreased elastase activity is important in the development of vascular changes and progressive pulmonary hypertension. ZD-0892 can suppress the elastase activity and completely reverse the fatal pulmonary hypertension induced by monocrotaline in rats.

Animals ; Hypertension, Pulmonary ; chemically induced ; drug therapy ; Male ; Monocrotaline ; toxicity ; Pancreatic Elastase ; antagonists & inhibitors ; Pulmonary Artery ; drug effects ; pathology ; physiopathology ; Pyrroles ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Sulfonamides ; pharmacology

OBJECTIVETo study the changes of peripheral plasmacytoid dendritic cells and lymphocyte subsets in patients with chronic hepatitis B (CHB) during consensus interferon (CIFN) treatment.

METHODSTwenty-three patients with CHB were treated with CIFN for 24 weeks and followed up for another 24 weeks. Peripheral plasmacytoid dendritic cells and lymphocyte subsets were measured throughout the treatment and follow-up periods.

RESULTSAfter CIFN treatment, 43.5% of the patients had virological and biochemical responses. The percentage and absolute number of peripheral plasmacytoid dendritic cells decreased significantly (P less than 0.05), the number of CD3+ cells, CD4+ T cells, B cells and the ratio of CD4+/CD8+ cells decreased also (P less than 0.05), but the number of CD8+ T cells and NK cells increased (P less than 0.05).

CONCLUSIONSConsistent virological and biochemical responses can be seen in some patients with CHB virus infection after CIFN treatment, and the percentage and number of their peripheral plasmacytoid dendritic cells greatly decreased, but the number of CD8+ T cells and NK cells increased.

Adult ; Antiviral Agents ; therapeutic use ; CD8-Positive T-Lymphocytes ; immunology ; Dendritic Cells ; immunology ; Female ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans ; Interferon-alpha ; therapeutic use ; Killer Cells, Natural ; immunology ; Male ; Young Adult

OBJECTIVETo evaluate the outcome of percutaneous balloon aortic valvuloplasty (PBAV) for severe aortic valve stenosis in infants younger than 3 months of age.

METHODSFour infants under the age of 3 months (ranged from 34 to 87 days) underwent PBAV for severe aortic stenosis between June 2010 and March 2011 were included in this study. The weight of infants ranged from 2.8 to 4.8 kg. The peak systolic valve gradient, left ventricular ejection fraction (LVEF) and aortic regurgitation were measured in all patients just before and immediately after balloon dilation respectively. Patients were followed-up up to 1 month after PBAV.

RESULTSThe aortic annulus diameter ranged from 7.0 to 8.8 mm. The ratio of balloon to aortic annulus diameter ranged from 0.86 to 1.00. PBAV was successful in all cases. The peak systolic valve gradient measured by Doppler echocardiography was (60.6 ± 15.2) mm Hg (1 mm Hg = 0.133 kPa) and LVEF was (47.6 ± 7.5)% before PBAV. Immediately after PBAV, the peak systolic valve gradient decreased to (29.5 ± 8.0) mm Hg (P < 0.01) and LVEF increased to (52.2 ± 18.9)% (P > 0.05). Two patients experienced significant bradycardia during PBAV and restored normal cardiac rhythm after cardiopulmonary resuscitation. At 1 month after PBAV, the peak systolic valve gradient measured by Doppler echocardiography was (36.5 ± 11.0) mm Hg (P < 0.05 vs. pre-PBAV) and LVEF was (81.0 ± 1.1)% (P < 0.01 vs. pre-PBAV). Only trivial to mild aortic regurgitation was detected post PBAV in the 4 patients.

CONCLUSIONPBAV is a feasible palliative procedure for infants with isolated aortic valve stenosis without annular or ventricular hypoplasia.

Aortic Valve Stenosis ; surgery ; Balloon Valvuloplasty ; Catheterization ; methods ; Female ; Humans ; Infant ; Male ; Treatment Outcome

Animals ; Female ; Guinea Pigs ; Kidney ; microbiology ; pathology ; Leptospira interrogans ; isolation & purification ; pathogenicity ; Leptospirosis ; microbiology ; pathology ; Liver ; microbiology ; pathology ; Lung ; microbiology ; pathology ; Male ; Time Factors

OBJECTIVEThe assessment of pulmonary vascular reactivity plays an important role in the management of idiopathic pulmonary arterial hypertension (IPAH). The aim of this study was to explore the indications and methodology of pulmonary vasodilator testing in children with IPAH.

METHODSFrom October 2009 to June 2011, a cohort of pediatric patients with IPAH in WHO functional classes II to III were enrolled in the study. Right heart catheterization was performed in all patients. After baseline hemodynamics were obtained, adenosine infusions were started at a dose of 50 µg/(kg·min), increased by 25 µg/(kg·min) at 2 min intervals to a maximum of 250 µg/(kg·min) or until a positive acute response.

RESULTSA total of 15 patients with IPAH were enrolled in the study. The mean age of the patients was 6.3 yrs. Mean pulmonary artery pressure (mPAP) was (67.1 ± 15.9) mm Hg. Pulmonary capillary wedge pressure (PCWP) was (9.7 ± 2.9) mm Hg. Pulmonary vascular resistance index (PVRI) was (17.9 ± 7.5) Wood U·m(2). Three patients were responders, defined as a fall in mPAP of at least 10 mm Hg to a pressure level of 40 mm Hg or lower. Twelve patients were nonresponders according to the same criteria. Five out of the 15 patients experienced adverse effects, including chest discomfort (n = 1), systemic hypotension (n = 3) and bradycardia (n = 1). All side effects abated within 30-60 s of the discontinuation of the adenosine infusion.

CONCLUSIONAdenosine is an effective vasodilator in children with IPAH and can be used for safe and rapid assessment of vasodilator reserve in these patients.

Adenosine ; Adolescent ; Child ; Child, Preschool ; Familial Primary Pulmonary Hypertension ; Female ; Humans ; Hypertension, Pulmonary ; physiopathology ; Infant ; Male ; Pulmonary Artery ; physiopathology ; Pulmonary Wedge Pressure ; Vascular Resistance ; Vasodilator Agents

BACKGROUNDThe RhoA/Rho kinase pathway may participate in the pathogenesis of hypoxia and monocrotaline induced pulmonary hypertension. This study tested whether RhoA/Rho kinase pathway is involved in the pathogenesis of high flow induced pulmonary hypertension in rats.

METHODSMale Wistar rats (4 weeks) were randomly divided into 4 shunt groups, 4 treated groups and 4 control groups. Shunt and treated groups underwent left common carotid artery/external jugular vein shunt operation. Control groups underwent sham operation. Treated groups received fasudil treatment and the others received same dose of saline. At weeks 1, 2, 4 and 8 of the study, right ventricular systolic pressure was measured and blood gases were analysed to calculate Qp/Qs. The weight ratio of right ventricle to left ventricle plus septum and the mean percentage of medial wall thickness in moderate sized pulmonary arteries were obtained. RhoA activity in pulmonary arteries was detected using Rho activity assay reagent. Rho kinase activity was quantified by the extent of MYPT1 phosphorylation with Western blot. Proliferating cells were evaluated using proliferating cell nuclear antigen immunohistological staining.

RESULTSCarotid artery/jugular vein shunt resulted in high pulmonary blood flow, both an acute and a chronic elevation of right ventricular systolic pressure, significant medial wall thickening characterized by smooth muscle cells proliferation, right ventricular hypertrophy and increased activation of RhoA and Rho kinase. Fasudil treatment lowered pulmonary artery systolic pressure, suppressed pulmonary artery smooth muscle cells proliferation, attenuated pulmonary artery medial wall thickening and inhibited right ventricular hypertrophy together with significant suppression of Rho kinase activity but not Rho activity.

CONCLUSIONSActivated RhoA/Rho kinase pathway is associated with both the acute pulmonary vasoconstriction and the chronic pulmonary artery remodelling of high flow induced pulmonary hypertension. Fasudil treatment could improve pulmonary hypertension by inhibiting Rho kinase activity.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ; analogs & derivatives ; therapeutic use ; Animals ; Cell Proliferation ; drug effects ; Enzyme Activation ; drug effects ; Hypertension, Pulmonary ; drug therapy ; etiology ; Hypertrophy, Right Ventricular ; prevention & control ; Intracellular Signaling Peptides and Proteins ; antagonists & inhibitors ; physiology ; Male ; Muscle, Smooth, Vascular ; drug effects ; Protein Kinase Inhibitors ; therapeutic use ; Protein-Serine-Threonine Kinases ; antagonists & inhibitors ; physiology ; Pulmonary Artery ; pathology ; Pulmonary Circulation ; drug effects ; Rats ; Rats, Wistar ; Systole ; drug effects ; Vasoconstriction ; drug effects ; rho-Associated Kinases ; rhoA GTP-Binding Protein ; physiology

BACKGROUNDFamilial pulmonary arterial hypertension (FPAH) is an autosomal dominant disorder characterized by plexiform lesions of endothelial cells in pulmonary arterioles which leads to elevated pulmonary arterial pressure, right-sided heart failure and death. Heterozygous mutations in the bone morphogenetic protein type II receptor gene (BMPR2) have been found to underlie a majority of FPAH cases. More than 140 distinct mutations have been identified in FPAH cases and in idiopathic pulmonary arterial hypertension (IPAH) cases, but only one mutation has been reported in Chinese patients.

METHODSA three-generation pedigree of FPAH and another 10 patients with IPAH were collected. In the family, two of the 9 surviving and one deceased family member were diagnosed as FPAH. The entire protein-coding region and intron/exon boundaries of the BMPR2 gene were amplified by PCR using DNA samples from affected individuals. Direct sequencing of PCR products was performed on both the sense and antisense strands. To confirm the segregation of the mutation within the family and exclude the presence of the mutation in normal subjects, the relevant exon was amplified by PCR, followed by mutation-specific RPLP analysis.

RESULTSIn the Chinese pedigree with FPAH an A-to-T transition at position 1157 in exon 9 of the BMPR2 gene was identified which resulted in a Glu386Val mutation. We confirmed the segregation of the mutation within the family and excluded the presence of the mutation in a panel of 200 chromosomes from normal subjects. No mutation was detected in BMPR2 in the other 10 patients with IPAH.

CONCLUSIONSThis amino acid substitution occurs at a glutamic acid that is highly conserved in all type II TGF-beta receptors. The nearly invariant Glu forms an ion pair with an invariant Arg at position 491 thereby helping to stabilize the large lobe. Substitution of Arg at position 491 is the most frequently observed missense mutation in FPAH, but until now no mutations at position 386 have been found in FPAH. The predicted functional impact of the Glu386Val mutation and its absence in healthy controls support the mutation as the cause of FPAH.

Adolescent ; Amino Acid Sequence ; Bone Morphogenetic Protein Receptors, Type II ; genetics ; Child ; Child, Preschool ; Female ; Humans ; Hypertension, Pulmonary ; genetics ; Infant ; Male ; Molecular Sequence Data ; Mutation ; Pedigree