Objective To explore the activated brain region of acute epilepsy in cat model induced by pentylenetetrazol(FFZ)with manganese enhanced-functional MR imaging(ME-fMRI),and evaluate the application of ME-fMRI on localization of the activated brain.Methods Forty cats were divided into 4 groups by random number table method as epileptic A and B groups as well as control A and B groups. Cats of epileptic groups were injected with PTZ(55 mg/kg)intramuscularly,and those of control groups were injected with the saline at same dose.The behavior change in the epileptic and control group A was observed and electroencephalogram(EEG)was also undertaken.Cats of epileptic and control group B were performed ME-fMRI,and the percentage of the enhanced signal intensity was then calculated.Results After injection with PTZ(55 mg/kg)intramuscularly,epileptic seizure was all evoked,and then EEG recording showed spike-wave and polyspike-wave complexes.The neocortex of cats of epileptic group B was diffusely phanero-enhanced on ME-fMRI.The percent enhancement of signal intensity in cortex of frontal lobe,parietal lobe and occipital lobe was(34.6?5.7)% and that in cortex of temporal lobe with(22.9? 6.5)%,whereas those of control group B with(14.9?4.5)% and(11.6?3.2)% respectively.And there was significant difference between the above different localization of the brain in the two groups (t=-10.43,-5.46 respectively,P

BACKGROUNDThe level of c-Myc is closely associated with high pathological grade and the poor prognosis of gliomas. Vascular endothelial growth factor (VEGF) is the most important angiogenic factor that potently stimulates the proliferation and migration of vascular endothelial cells. This study aimed to address the biological importance of c-Myc in the development of gliomas, we downregulated the expression of c-Myc in the human glioblastoma cell line IN500 and studied the in vitro effect on cellular growth, proliferation, and apoptosis and the expression of VEGF and the in vivo effect on tumor formation in a xenograft mouse model.

METHODSIN500Δ cells were stably transfected with shRNA-expressing plasmids for either c-Myc (pCMYC-shRNA) or as a control (pCtrl-shRNA). Following establishment of stable cells, the mRNA expressions of c-Myc and VEGF were examined by reverse transcription (RT)-PCR, and c-Myc and VEGF proteins by Western blotting and immunohistochemistry. Cell-cycle progression and apoptosis were determined by flow cytometry. The in vivo effect of targeting c-Myc was determined by subcutaneous injection of stable cells into immunodeficient nude mice.

RESULTSThe stable transfection of pCMYC-shRNA successfully knocked down the steady-state mRNA and protein levels of c-Myc in IN500, which positively correlated with the downregulation of VEGF. Downregulating c-Myc in vitro also led to G1-S arrest and enhanced apoptosis. In vivo, targeting c-Myc reduced xenograft tumor formation and resulted in significantly smaller tumors.

CONCLUSIONSc-Myc has multiple functions in glioblastoma development that include regulating cell-cycle, apoptosis, and VEGF expression. Targeting c-Myc expression may be a promising therapy for malignant glioma.

Animals ; Apoptosis ; genetics ; physiology ; Cell Cycle ; genetics ; physiology ; Cell Line, Tumor ; Female ; Flow Cytometry ; Glioblastoma ; genetics ; metabolism ; therapy ; Humans ; Immunohistochemistry ; Mice ; Mice, Nude ; Proto-Oncogene Proteins c-myb ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; Xenograft Model Antitumor Assays

Background The level of c-Myc is closely associated with high pathological grade and the poor prognosis of gliomas.Vascular endothelial growth factor (VEGF) is the most important angiogenic factor that potently stimulates the proliferation and migration of vascular endothelial cells.This study aimed to address the biological importance of c-Myc in the development of gliomas,we downregulated the expression of c-Myc in the human glioblastoma cell line IN500 and studied the in vitro effect on cellular growth,proliferation,and apoptosis and the expression of VEGF and the in vivo effect on tumor formation in a xenograft mouse model.Methods IN500△ cells were stably transfected with shRNA-expressing plasmids for either c-Myc (pCMYC-shRNA) or as a control (pCtrl-shRNA).Following establishment of stable cells,the mRNA expressions of c-Myc and VEGF were examined by reverse transcription (RT)-PCR,and c-Myc and VEGF proteins by Western blotting and immunohistochemistry.Cell-cycle progression and apoptosis were determined by flow cytometry.The in vivo effect of targeting c-Myc was determined by subcutaneous injection of stable cells into immunodeficient nude mice.Results The stable transfection of pCMYC-shRNA successfully knocked down the steady-state mRNA and protein levels of c-Myc in IN500,which positively correlated with the downregulation of VEGF.Downregulating c-Myc in vitro also led to G1-S arrest and enhanced apoptosis.In vivo,targeting c-Myc reduced xenograft tumor formation and resulted in significantly smaller tumors.Conclusions c-Myc has multiple functions in glioblastoma development that include regulating cell-cycle,apoptosis,and VEGF expression.Targeting c-Myc expression may be a promising therapy for malignant glioma.

OBJECTIVETo observe the effects of beta3-adrenergic receptor(beta3-AR) antagonist on myocardial uncoupling protein 2 (UCP2) expression and energy metabolism in chronic heart failure rats.

METHODSSeven weight-matched normal adult rats (control group), 18 isoproterenol (ISO) induced heat failure (HR) rats (ISO group) and 21 ISO induced heart failure rats but received specific beta3-AR inhibitor SR59230A (ISO+ SR59230A group) for 6 weeks were included in this research. At the end of the study, echocardiography was performed, the ratio of left ventricular weight and body weight (LVW/BW) was calculated. The expression of beta3-AR ad UCP2 mRNA in myocardium were detected by reverse transcription-polymerase chain reaction (RT-PCR), the UCP2 protein in myocardium were detected by Western blot. The myocardial contents of creatine phosphate (PCr) and adenosine triphosphate (ATP) were measured by high performance liquid chromatography (HPLC).

RESULTSCompared with control group, the cardiac function was significantly reduced and myocardial beta3-AR mRNA significantly increased, UCP2 mRNA and protein were also significantly increased in ISO group, this change could be attenuated by the treatment with SR59230A, and the expression of myocardial UCP2 protein negatively correlated with the ratio of PCr/ATP.

CONCLUSIONIn the chronic stage of HF, the expression of UCP2 increases, which causes myocardial energy shortage, SR59230A improves myocardia energy efficiency and cardiac function by means of suppressing the expression of UCP2.

Adrenergic Antagonists ; pharmacology ; Animals ; Energy Metabolism ; Heart Failure ; metabolism ; Ion Channels ; metabolism ; Male ; Mitochondrial Proteins ; metabolism ; Myocardium ; metabolism ; Rats ; Rats, Wistar ; Receptors, Adrenergic, beta-3 ; metabolism ; Uncoupling Protein 2

OBJECTIVETo observe the effects of complement fragment C3f on expression and secretion of collagen I, III and transforming growth factor( TGF)-beta1 in human embryonic lung fibroblast (MRC-5) cells.

METHODSMRC-5 cells were cultured with C3f (the synthetic 17 peptides fragments of complement C3). The extracellular and intracellular expression levels of type I, III collagens and TGF-beta1 in MRC-5 cultures were detected by ELISA and immunohistochemistry, respectively.

RESULTSThe expression levels of type I, III collagen and TGF-beta1 in the supernatant of MRC-5 cultures decreased significantly with the concentrations of C3f as compared with controls (P < 0.05). Also the expression level of TGF-beta1 in MRC-5 cytoplasm reduced significantly as compared with controls (P < 0.05).

CONCLUSIONThe results of present in vitro study showed that the complement fragment C3f could reduce the formation of TGF-beta1 and type I, III collagens in MRC-5 cells, and inhibit the lung tissue fibrosis.

Cell Line ; Collagen Type I ; metabolism ; Collagen Type III ; metabolism ; Complement C3b ; pharmacology ; Fibroblasts ; drug effects ; metabolism ; Humans ; Lung ; cytology ; drug effects ; embryology ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVEBased on two sets of data from occupational epidemiology, Benchmark dose (BMD) was applied to estimate biological exposure limit (BEL).

METHODSCadmium exposed workers were selected from a cadmium smelting and a zinc products factory and control group was selected from doctors or nurses and staff from shops living in the same area; Urinary cadmium (UCd) was used as exposure biomarker and urinary beta(2) microglobulin (UBM), NAG (UNAG) and albumin (UALB) were as effect biomarkers. All urine parameters were adjusted by urinary creatinine. Software of BMDS (Version 1.3.2, EPA.U.S) was used to calculate BMD.

RESULTSCalculated abnormal prevalence was based on the upper limit of 95% of effect biomarkers in control group; There are significant dose response relationship between the prevalence of effect biomarkers (UBM, UNAG and UALB) and exposure biomarker (UCd); BEL was 5 microg/g creatinine for UBM as effect biomarker, It consists with the recommendation of WHO; BEL was 3 microg/g creatinine for UNAG as effect biomarker; BEL can be estimated by using the method of BMD; the more sensitive biomarker would used, the more occupational people would protected.

CONCLUSIONThe application of BMD in estimating biological exposure limit (BEL) is proper. UNAG is suggested as most sensitive biomarker to be used to estimate BEL for cadmium exposure.

Acetylglucosaminidase ; urine ; Albuminuria ; urine ; Biomarkers ; urine ; Cadmium ; adverse effects ; urine ; Dose-Response Relationship, Drug ; Female ; Humans ; Male ; Occupational Exposure ; Reference Values ; beta 2-Microglobulin ; urine

Adult ; Calcaneus ; injuries ; surgery ; Female ; Fractures, Bone ; surgery ; Humans ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; Young Adult

AIM To optimize the subcritical aqueous extraction for polysaccharides from the leaves of Punica granatum L.and to evaluate the in vitro antioxidant activity.METHODS With reaction pressure,solid-liquid ratio,extraction time and extraction temperature as influencing factors,yield of polysaccharides as an evalution index,the extraction was optimized by Box-Behnken method on the basis of single factor test.Then the scavenging effects of polysaccharides on hydroxyl free radical,superoxide anion and DPPH free radical were detected.RESULTS The optimal conditions were determined to be 5 MPa for reaction pressure,1 ∶ 27 for solid-liquid ratio,11 min for extraction time,and 155 ℃ for extraction temperature,the yield of polysaccharides was 1.809％.There was a dose-effect relationship between scavenging rate and polysaccharides' concentration.0.1 mg/mL Polysaccharides displayed the strongest scavenging effects on hydroxyl free radical,superoxide anion and DPPH free radical with the clearance rates of 57.36％,70.51％ and 58.02％,respectively.CONCLUSION This stable and reliable method can be used for the subcritical aqueous extraction for polysaccharides from P.granatum leaves with obvious in vitro antioxidant activity.

Objective To compare the clinical effect of aripiprazole and risperidone in patients with schizophrenia and metabolic syndrome.Methods A retrospective analysis was performed on the case data of schizophrenia and metabolic syndrome.According to different treatment methods,they were divided into risperidone group(oral risperidone,2 mg once,twice a day)and aripiprazole group(oral aripiprazole,5 mg once,once a day).All were treated for 24 weeks and given lifestyle intervention.The clinical effect,scores of positive and negative symptom scale(PANSS),metabolic syndrome-related indexes[systolic blood pressure(SBP),diastolic blood pressure(DBP),body mass index(BMI),fasting blood glucose(FPG),triglyceride(TG)],cognitive function[MATRICS consensus cognitive battery(MCCB)],levels of serum brain-derived neurotrophic factor(BDNF),tyrosine kinase receptor B(TrkB)and glial cell line-derived neurotrophic factor(GDNF)were compared between the two groups.The adverse drug reactions were statistically analyzed in two groups.Results There were 60 cases in risperidone group and 60 cases in aripiprazole group.The total response rates of aripiprazole group and risperidone group were 91.67％and 76.67％,with significant difference(P＜0.05).After treatment,scores of positive symptoms in PANSS in aripiprazole group and risperidone group were(10.04±1.55)and(11.52±1.62)points;negative symptom scores were(12.74±2.38)and(14.38±2.25)points;general psychopathology scores were(16.53±4.39)and(19.76±4.10)points;total scores of PANSS were(39.31±6.25)and(45.66±6.71)points;total scores of MCCB were(43.61±8.50)and(40.55±8.16)points;BMI were(24.05±2.52)and(25.73±2.86)kg·m-2;SBP were(123.61±7.64)and(128.75±8.59)mmHg;FPG were(5.69±0.60)and(6.38±0.62)mmol·L-1;TG levels were(1.76±0.20)and(2.01±0.22)mmol·L-1;levels of serum BDNF were(32.41±5.81)and(28.65±4.87)pg·mL-1;TrkB levels were(43.88±5.92)and(41.73±5.63)ng·mL-1;GDNF levels were(587.47±36.12)and(468.23±35.68)pg·mL-1,the differences between the two groups were all statistically significant(all P＜0.05).There was no significant difference in the incidence of adverse drug reactions between aripiprazole group and risperidone group(15.00％vs.6.67％,P＞0.05).Conclusion Compared with risperidone,clinical effect of aripiprazole is better in patients with schizophrenia and metabolic syndrome,which has fewer effects on body weight,blood pressure and glycolipid metabolism,and it may improve cognitive function by increasing levels of serum BDNF,TrkB and GDNF.

BACKGROUND AND PURPOSE: Vasa vasorum (VV) have been believed to be rare or non-existent in small-caliber intracranial arteries. In a series of human cerebral artery specimens, we identified and examined the distribution of VV in association with co-existing intracranial atherosclerosis. METHODS: We obtained cerebral artery specimens from 32 consecutive autopsies of subjects aged 45 years or above. We scrutinized middle cerebral artery (MCA), vertebral artery (VA), and basilar artery (BA) for the presence of adventitial VV. We described the distribution of VV, and the characteristics of co-existing atherosclerotic lesions. RESULTS: Among 157 intracranial arteries, adventitial VV were present in 74 of the 157 specimens (47%), involving MCA (n=13, 18%), BA (n=14, 19%), and VA (n=47, 64%). Although qualitatively these 74 adventitial VV distributed similarly in arteries with or without atherosclerotic lesions (disease-free arteries n=4/8; arteries of pre-atherosclerosis n=17/42; and arteries of progressive atherosclerosis n=53/107), the presence of adventitial VV in intracranial VA was associated with a heavier plaque load (1.72±1.66 mm2 vs. 0.40±0.32 mm2, P < 0.001), severer luminal stenosis (25%±21% vs. 12%±9%, P=0.002), higher rate of concentric lesions (79% vs. 36%, P=0.002), and denser intraplaque calcification (44% vs. 0%, P=0.003). Histologically, intracranial VA with VV had a larger diameter (3.40±0.79 mm vs. 2.34±0.58 mm, P < 0.001), thicker arterial wall (0.31±0.13 mm vs. 0.23±0.06 mm, P=0.002), and a larger intima-media (0.19±0.09 mm vs. 0.13± 0.04 mm, P=0.003) than VA without VV. CONCLUSIONS: Our study demonstrated the distribution of adventitial VV within brain vasculature and association between vertebral VV and progressive atherosclerotic lesions with a heavier plaque load and denser intraplaque calcification.
Arteries ; Atherosclerosis ; Autopsy ; Basilar Artery ; Brain ; Cerebral Arteries ; Constriction, Pathologic ; Humans ; Intracranial Arteriosclerosis* ; Middle Cerebral Artery ; Phenobarbital ; Vasa Vasorum* ; Vertebral Artery