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Objective:To observe the expression of BTLA on T cells during activation and further analyze its inhibitory effects on T cell activation in different phases.Methods: T cells from PBMC were enriched by negative selection using magnetic beads.Expression of BTLA,CTLA-4 and PD-1 on freshly isolated human T cells and kinetics expression of BTLA,CILA-4 and PD-1 on CD3 mAb stimulated T cells were examined by flow cytometry.T cells were stimulated by anti-CD3 mAb combined with anti-CD28 mAb in the presence of anti-BTLA mAb 8H9,then T cell proliferation was tested by MTT assay in the different culture time.Immature DCs were generated from monocytes cultured in the medium containing GM-CSF and IL-4, and further driven to maturation by anti-CD40 mAb.Expression of HVEM on DCs was measured by flow cytometry.T cells were co-cultured with DCs in the presence of soluble 8H9 or anti-HVEM antibody to block HVEM-BTLA interaction,T cell proliferation was measured by MTT assay.Results:Freshly isolated T cells exhibited high levels of BTLA expression, but not CTLA-4 and PD-1.After T cell activation, BTLA expression decreased on first 2 days, with rapidly increasing to high levels.Unlike BTLA, expression of CTLA-4 and PD-1 was gradually increased during T cell activation.8H9 significantly inhibited the proliferation of T cell stimulated by CD3 mAb and CD28 mAb.8H9 could still exhibit inhibitory effect on T cell proliferation after 24 h or 48 h of preactivation by CD3 mAb plus CD28 mAb stimulation.HVEM was highly expressed on immature DCs, and down-regulated on mature DCs.Blockade of BTLA by soluble 8H9 or anti-HVEM antibody enhanced DC-mediated T cell proliferation within 48 h.Conclusion: BTLA signal enhances the threshold of T cell activation and plays importantly negative regulatory role in the initiation and early phase of T cell activation.
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Intracranial pressure fluctuates due to heart beat, respiration, neuro-regulation, etc. Traditional intracranial pressure study focuses on the static pressure and related factors, putting emphasis on mean intracranial pressure, while paying little attention to the pulse components. This study was composed of two parts: animal experiment and theoretical analysis. The animal experiment was performed on 14 mongrel dogs, studying the variation of intracranial pressure wave form under different intracranial pressure level. The dogs were installed epidurally with latex sacculus to establish models of increased intracranial pressure. The degree of intracranial pressure and volume could be altered by changing the volume of fluid in the sacculus. During the process, pressure transducers were arranged to monitor and record the variations of the pressure of intracranial ventricle and lumbar subarachnoid cavity. The result demonstrated that, with the continual increase of intracranial pressure, intracranial pulse pressure increased correspondingly, showing a linear relationship with the change of intracranial pressure. After the sacculus was emptied and reinfused, the slope of the linear relationship was determined to be greater than the former slope. The same result was obtained in the lumbar cerebrospinal fluid pressure. Therefore, the lumbar cerebrospinal fluid pressure is consistent with the intracranial pressure. Intracranial pulse pressure is in linear relationship with mean pressure, and the slope of their linear relationship predicts the perform of intracranial autoregulation.
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Animals , Dogs , Female , Male , Blood Pressure , Physiology , Cerebrospinal Fluid Pressure , Physiology , Intracranial Pressure , Physiology , Monitoring, Physiologic , Methods , Pulsatile Flow , Physiology , PulseABSTRACT
BACKGROUND: Since the discovery of the fact that activin can promote the survival of retinal neurocyte in chicken,the effects of activin in nervous system receives recognition. As discovered recently,hippocampal activin βA mRNA expression up-regulates in multiple brain injury animal models including ischemia and hypoxia; however,the change of activin βA mRNA expression after epilepsy is waiting for investigation.OBJECTIVE: To observe hippocampal activin βA mRNA expression at different time point after pilocarpine (PC) -induced epilepsy in mouse to explore its mechanism.DESIGN: A randomized controlled experimental study based on the experimental animals.SETTING: Department of neurology in a university affiliated hospital and the institute of neurology in a university.MATERIALS: The study was conducted in the Institute of Neurology of Huashan Hospital Affiliated to Fudan University and the Department of Pathology of Shanghai Medical College between November 2001 and July 2002. Totally 168 eight to ten-week old healthy male C57BL/6 mice with a body mass between 20 g and 25 g were obtained from Shanghai Experimental Animal Center,Chinese Academy of Science.INTERVENTIONS: 350 mg/kg(10 g/L) of PC was injected into the abdominal cavity in the mice of study group,in which 1 mg/kg of scopolamine (SC) was injected at 30 minutes before the injection of PC to antagonize its peripheral cholinergic reaction. Status epilepticus(SE) model mouse was the mouse with continuous mgoelonus or generalized seizure of rigid clonus that lasted for 1 hour after the injection of PC. Valium(4 mg/kg) was immediately injected after the modeling to terminate seizure. Same dose of Valium was injected into non-SE(NSE) mice after 1.5 hours of PC injection. Saline was used to replace PC to inject into mice of control group,and the rest disposals of control group were as same as that of study group. SE mice,NSE mice and control mice were randomly divided into six subgroups including 0hour,1 hour,3 hours,6 hours,24 hours and 48 hours subgroups according to the time point after modeling with 6 mice of each subgroup(mice of NSE group and subgroups of 0 hour time point were not included into analysis of hybridization in situ).MAIN OUTCOME MEASURES: Hippocampal activin βA mRNA expression of different time point in SE mice and NSE mice were observed by RT-PCR; the distribution of hippocampal activin βA mRNA expression at different time points in mice were observed by hybridization in situ.RESULTS: There was no significant change of hippocampal activin βA mRNA expression at different time point in mice of NSE group and control group. In SE group,activin βA mRNA(0.49 ± 0. 11) had a transient significant decrease at the beginning(0 hour),which rapidly returned to control level(0. 74 ±0. 13) at 1 hour(0.73 ±0. 12) . Activin βA mRNA continuously increased and reached (0.97 ±0. 24) at 3 hours,(1.34 ±0. 19) at 6 hours,maintained (0.98 ±0. 17) until 24 hours,and decreased to (0. 83 ± 0.09) at 48 hours afterwards,which was slightly higher than control level. Compared with control group,the increases at 3 hours,6 hours and 24hours were significant( t = 2. 668,6. 289,2. 916,P ＜ 0. 001 - 0. 05). The significant up-regulation of activin βA mRNA expression was occurred earliest in hippocampal CA2 and DG regions at 3 hours after SE,and the significant expressions also could be seen in CA3 region after 6 hours. There were expressions in only CA2 and CA3 regions after 24 hours,while there were very few positive cells in CA2 region after 48 hours.CONCLUSION: PC-induced SE could significantly up-regulate hippocampal activin βA mRNA expression,while NSE has no such up-regulative effect. The up-regulation of hippocampal activin βA mRNA expression might be an endogenous protective effect of neuron on antagonizing excitatory injury.
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10 beats/min) to be with frequent monomorphic ventricular ectopic beats originating in the right outflow tract. Using activation-mapping for the earliest endocardial activation of spontaneous monomorphic ventricular ectopic beats, the site was ablated by RFCA.Results The immediate successful rate was 100% (28/28). Holter monitoring before and after ablation found monomorphic ventricular ectopic beats:15.836-32.419 beats/24 h vs 0-1.236 beats/24 h.Following-up of 6-24 months found all the 28 patients living in normal state.No complication occurred.Conclusion RFCA of frequent monomorphic ventricular ectopic beats originating in the right outflow tract is safe and effective.
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ObjectiveTo detect the features of dopamine secretion of cultured bovine retinal pigmentary epithelial(RPE) cells. The level of dopamine and survival rate after passage and microencapsulation were also observed. MethodsThe primary culture of bovine RPE cells was made using enzyme digestion. After purification and identification the growth curve of the cell was observed. Alginate-polylysine-alginate(APA) microencapsulated cells were made with a high voltage electostatic system. The activity of the cells in the mirocapsule was investigated by trypan blue staining. The secretion of dopamine was determined by high performance liquid chromatography (HPLC) assay. ResultsThe cell had high purity of immunocytochemistry. The growth curve showed that the exponential growth occurred at the first 1~4 days. Dopamine content was first detected at the time point of 2 hour, and arrived at the peak at about 48 hour of the cultivation. The secretion of dopamine was not different between passages. Dopamine secretion was dramatically decreased in the first 4 days after microencapsulation (P
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Purpose To investigate the influence of paraquat on substantial nigra and doparine levels ofstriatum in C57BL mice. Methods 39 neonatal C57BL mice were randomly divided into 5 groups andwere given paraquat or 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine(MPTP) orally in 10 th and 11 thdays odl; ( 1 ) MPTP 0.3 mg/kg, n = 8; (2) MPTP 20 mg/kg, n = 8; (3) paraquat 0.07 mg/kg, n = 8; ( 4 )paraquat 0.36 mg/kg, n = 8; (5) normal saline, n = 7. Adult spontaneous motor activity was observed atages of 120 days, then the mice were decapitated and the contents of dopamine(DA), serotonin(5-HT), andtheir metabolites in striatum were analyzed. Meanwhile, the dopamine neuons at the mesencephalon vereobserved by the method of ABC immunohistochemistry. Results Mice given Paraquat 0.36 mg/kg andMPTP 20 rng/kg showed a marked bypoactive behavior and reduced the striatal contents of DA andmetabolites without affecting 5-HT. Immunohistochemical staining showed that the amount of dopamineneurons at the midbrain decreased. Conclusions C57BL mice exposed to great amount of paraquat duringthe neonatal period could yield the alterations of behavior and some pathological and biochemical changessimilar to parkinson disease.
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AIM: To study the efficacy and safety of dispersible formulation of levodopa-benserazide on the parkinson disease. METHODS: The multicenter, open-label, self-controlled trial was conducted at 23 hospitals in 15 cities. Two hundred and four patients with idiopathic parkinson who had received standard levodopa-benserazide previously participated in this study. Dispersible levodopa-benserazide instead of standard levodopa-benserazide for 8 wk as a course. The Webster rating scale and patient diary were applied to assess the efficacy and safety of dispersible levodopa-benserazide. RESULTS： The medication with dispersible levodopa-benserazide increased “on” time by 47 min, decreased “off” time by 11 min, and speeded the onset of “on” time by 37 min. The Webster score was improved by 25 %. Statistical significant difference was calculated (P<0.01). Slight and few adverse reactions were found. CONCLUSION: Dispersible formulation of levodopa-benserazide is a powerful anti-parkinsonian drug characterized by oral easy use and rapid reach to therapeutic action after ingestion. This drug is particularly used in the parkinsonian patients with morning akinesia, delayed onset of “on” time, afternoon “off” status and dysphagia.
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Objective To study the role of ventricular responses(VR) in radiofrequency catheter ablation (RFCA) of idiopathic ventricular tachycardia(VT).Methods Thirteen patients underwent RFCA by using a combination of surface ECG,activition mapping and VR.The ablation targets were primarily selected by activition mapping and was determined by the VR in RFCA,and then,the final ablation target was determined and ablated where VR and VT had the same ECG results.Results Thirteen patients were successfully ablated.The VRs showed:the VR induced by RFCA in sinus rhythm was just the same as VT;intermittent sinus rhythm appeared between VT;two couple or couplets,or premature beats appeared intermittently in sinus rhythm,and finally sinus rhythm appeared;the VR induced by RFCA was not the same as VT.Conclusion The ablation target should be the site where the VR induced by RFCA is just the same as VT;the occurence of VR that is just the same as VT can be the predictor of successful ablation.
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Objective To explore whether the dopamine D1 and D2 receptors were involved in pathogenic mechanism of Parkinsonian mice induced by paraquat. Methods The models of Parkinson's mice were induced by oral paraquat. The levels of dopamine D1 and D2 receptor proteins and the expression of receptor mRNAs in striatum were examined by immunohistochemistry and in situ hybridization, respectively. Results Mice treated by oral paraquat (10mg?day -1 ?kg -1 ) for four months displayed marked hypoactive behavior. The levels of dopamine D1 and D2 receptor proteins in the striatum were significantly decreased by 28% and 29%, respectively (P
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Objective To set up the Parkinson's disease(PD)rat model with pathologic characteristic of Lewy body in nigral cells.Methods SD rats were injected respectively with 8 mg Lactacystin(Lactacystin group),sodium saline(NS group)and 12 mg 6-OHDA(6-OHDA group)by stereotaxic unilateral injection into the pars compacta of substantia nigral.The spontaneous and apomorphine-induced contralateral behaviors of rats were observed.The changes of midbrain histology were viewed by microscope;expression of ?-synuclein and tyrosine hydroxylase(TH)positive cells were investigated by immunohistochemistry.The contents of dopamine and homovanillic acid in striatum were determined.Results Rats of NS group did not display abnormal behavior.The animals treated with Lactacystin developed progressively bradykinesia,hypokinesia,tremor,contralateral head tilting,and displayed apomorphine-induced contralateral rotation behavior;3 weeks later the number of TH positive cells were decreased by 83.29% compared with NS group(P
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Objective The clinical efficacy and safety of L dopa monotherapy and concomitant L dopa therapy with dopamine agonists (bromocriptine or pergolide) of the treatment of Parkinson's disease Methods The clinical trial was performed in the multicentre,open label study L dopa group: 47 cases,L dopa plus bromocriptine group: 43 cases and L dopa plus pergolide group: 48 cases The clinical efficacy was assessed with modified Webster's scale and motor dysfunction rating scale for Parkinson's disease ( MDRSPD ),and safety data included blood hepatic and renal function tests,blood and urine routine tests,arterial blood pressure,heart rate measurements and electrocardiogram were also analyzed at the beginning and end of study The average daily dose of L dopa in levedopa group was (523 3?235 9) mg,The average daily dose of L dopa and bromocriptine were (526 7?241 3) mg and (7 3?1 5) mg in L dopa plus bromocriptine group,respectively The average daily dose of L dopa and pergolide were (558 3?192 9)mg and (0 235?0 045) mg in L dopa plus pergolide group separately Result The clinical improvement was about 74 5%both in assessment of modified Webster's scale and MDRSPD in L dopa group The clinical score was improved in 69 8% (Webster's scale) and 79 1% (MDRSPD) in L dopa plus bromocriptine group,respectively The clinical improved rates were 77 9%( Webster's scale ) and 81 3%( MDRSPD ) in L dopa plus bergolide group The incidence rates of side effects were 27 7%in L dopa group,39 5%in L dopa plus bromocriptine and 18 8%in L dopa plus pergolide groups Conclusion There was an efficacy in treatment of Parkinson's disease in either L dopa monotherapy or combination with bromocriptine or pergolide The treatment of L dopa alone was more effective in the early stage of Parkinson's disease and concomitant L dopa therapy with dopamine agonists were more effective in the advanced stage of Parkinson's disease,pergolide was not only more effective,safe and tolerable,but also fewer adverse events than Bromocriptine was in this short term trial
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Objective To study the effect of proteasome on nigral degeneration and Lewy body formation. Methods By stereotaxic unilateral injection of different doses of lactacystin, a selective proteasome inhibitor, into the substantia nigral pars compacta of rats, the spontaneous and apomorphine induced contralateral behaviors of rats were observed. Nigral degeneration and Lewy body were viewed by HE staining; expressions of ? synuclein and tyrosine hydroxylase in nigral cells were investigated by immunohistochemistry. Contents of dopamine and homovanillic acid were determined by HPLC. Results There were no difference between 0 2 ?g group and control. Animals treated with 2 ?g and 8 ?g lactacystin developed progressively bradykinetic and displayed contralateral head tilting and tremor; apomorphine induced contralateral behavior was notably observed in rats of 8 ?g group; 3 weeks later, nigral degeneration were present in 2 ?g and 8 ?g groups; some of nigral cells contained acidophilic Lewy body with intense immune response to ? synuclein; the number of tyrosine hydroxylase positive cells in 2 ?g and 8 ?g groups were decreased by 68 24% ( P
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Objective To study the efficacy and safety of entacapone as an adjunct to levodopa treatment in pakinsonian patients with wearing-off motor fluctuations. Methods A total 209 pakinsonian patients with end-of-dose deterioration participated in a multi-center,12-weeks randomized,placebo-controlled,double blind,parallel-group trial.The efficacy of entacapone was assessed using the patient’s diary card,the Unified Parkinson’s Disease Rating Scale (UODRS) score,the daily levodopa dosage,and the global assessment of changes.Results 96.2% of the entacapone and 92.4% of the placebo-treated patients completed the study.In 209 cases of the ITT population,in comparison to the placebo-treated patients,entacapone had increased the mean “on” time (h/d) from 7.4?1.8 in base-line to 9.1?2.5 in week 12,decreased the “fof” time (from 6.8?2.2 in base-line to 5.2?2.8 in week 12),improved the motor scores (from 36.7?11.3 in base-line to 30.0?14.4 in week 12),and reduced the levodopa dose (from 589.2?264.3 in base-line to 561.5?248.1 in week 4). The improvement was also evident on impression of successful treatment for 69.9% of neurologists through global change assessment.There was no significant difference in the frequency of dopaminergic adverse events and serious laboratory abnormalities between entacapone and placebo groups.Conclusion The results of this study demonstrate that entacapone,the COMT inhibitor is a safe and effective extender of levodopa treatment for Parkinson’s disease patients with motor flucturations.
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Objective To investigate the relationship between the variation of cerebrospinal fluid pulse pressure and that of intracranial perfusion pressure during the process of increasing intracranial pressure.Methods Fourteen dogs were installed epidurally with latex sacculus to establish models of increased intracranial pressure. The degree of intracranial pressure and volume could be altered by changing the volume of fluid in the sacculus. During the process, pressure transducers were arranged to monitor and record the systematic blood pressure and the variation of the pressure of cerebral ventricle and lumbar subarachnoid space.Results With the continual increasement of intracranial pressure, the cerebral perfusion pressure decreased, and the cerebrospinal fluid pulse pressure correspondingly increased. A positive linear relationship between the variation of intracranial pressure and that of cerebrospinal fluid pulse pressure and a negative linear relationship between the variation of cerebral perfusion pressure and that of cerebrospinal fluid pulse pressure were found.Conclusion During the experimental process of increased intracranial pressure, with the decrease of cerebral perfusion pressure , the cerebrospinal fluid pulse pressure increases. The relationship of variations between them shows a negative linear one. It seems that in the circumstances when the autoregulation of cerebral vessel is injured, the variations of cerebrospinal fluid pulse pressure may produce some useful information as to the changes of intracranial blood flow.
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Objective To study the therapeutic efficacy of dopaminergic agonists,? dihydroergocriptin(Cripar) by multiple center opened trial Methods Sixty cases of Parkinson's disease were divided into two groups: monotherapy group(27 cases) and combined therapy group(33 cases) The improvement in both groups after therapy was observed Results Patients undergone monotherapy were treated with ? dihydroergocriptin and those undergone combined therapy were treated with combined use of ? dihydroergocriptin and L doparmine All patients after treatment showed improvement of clinical symptoms There were 7 patients (28 0%) in the monotherapy group and 13 patients (39 4%) in the combined therapy group markedly improved Evaluation of therapeutic improvement by modified UPDRS revealed that the average scores was 5 01 in monotherapy group and was 6 39( P
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Objective To evaluate the protective role of bone marrow stromal cells (BMSCs) to lactacystin-Parkinson's disease (PD) rats.Methods BMSCs were obtained from adult male SD rats and were expanded, isolated and purified. BMSCs were harvested from 4 to 6 passage and used for transplantation. PD rats that expressed Lewy body and presented lateral rotation were made by injecting 8?g lactacystin into one side of substantia nigra compact part of rat with stereotaxic technique. The rats were transplanted with BMSCs labelled by Brdu by stereotaxic unilateral injection into striatum and transplanted with normal saline as control. The behavior changes of rats and the expression of BDNF, migration, differentiation of BMSCs were examined.Results 71.43% of the rats displayed significant improvement of contralateral behavior after BMSCs transplantation, however there was no change in control group. BMSCs were found in several areas of the brain including striatum, corpus callosum and contralateral cortex. The implanted BMSCs expressed BDNF but no tyrosine hydroxylase.Conclusion BMSCs may play a neuroprotective role in lactacystin-PD rats by secreting BDNF.
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Objective To study the changes of low-frequency-component of intracranial pressure (ICP) fluctuation during intracranial hypertension. Methods 15 healthy mongrel dogs were used to make models of intracranial hypertension by arranging latex sacculus epidurally.The different amount of normal that was injected into latex sacculus led to fluctuation of ICP and alteration of intracranial volume. The pressures in ventricle and lumbar spinal canal were recorded continuously by baroceptor, and the changes of low-frequency-component of ICP fluctuation were studied by frequency-spectrum analysis. Results After increase of intracranial pressure and volume,pulse wave (M wave) with its frequency at 0.1～0.2 Hz showed continually. Conclusion Emerge of M wave may reflect some decrease of intracranial compliance and the beginning of volume compensation failure.
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Objective To observe the effects of MPP+ on the expression of inhibin, activin and its receptor ⅡA and cell ability in PC12 cells of rats.Methods The changes of expression of activin?A, activin?B, inhibin? and receptorⅡA mRNAs were assayed by RT-PCR, the change of cell viability was detect by tyrpan blue exclusion method in cultured PC12 cells at 3 h,6 h,12 h,24 h after MPP+ was added and compared with control groups.Results The expression of activin?A, activin?B and activin receptorⅡA mRNAs in PC12 cells were down-regulated significantly after MPP+ administrated at every time point while the expression of inhibin? mRNA remained unchanged. The cell viability decreased at the points of 12 h and 24 h after MPP+ administrated.Conclusion MPP+ may cause the injury of PC12 cells by downregulating the expression of activin and its receptor.