2001年 · 第114卷第03期

Objective To study the apoptotic effects of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) on the nigral dopaminergic neurons of mice and 1 -methyl-4-phenylpyridium ion (MPP+) on pheochromocytoma(PC12) cells, as well as the antagonism of Eldepryl against MPTP's apoptotic effect. Methods Three groups of C57BL mice were treated with MPTP, Eldepryl plus MPTP and normal saline,respectively, for 7 days before performing TUNEL (terminal deoxyneucleotidyl transferase-mediated dUTP-x nick end labeling) and FACS (fluorescence activated cell sorting) analyses of neuronal apoptosis in the substantia nigra. The same tests were employed in cell culture to examine apoptosis in PC12 cells treated with MPP+, MPTP or PBS. Results Intraperitoneal administration of MPTP 30 mg/kg could induce nigral apoptosis, and oral use of Eldepryl prior to MPTP treatment could completely prevent the nigral apoptosis caused by MPTP. MPP+,an intermediate metabolite of MPTP, could lead to the apoptosis of PC12 cells, whereas MPTP itself had no such effect on PC12 cells. Conclusions The experiment indicated that the neurotoxin, MPTP, might cause the death of nigral neurons through a mechanism of apoptosis and this effect might be mediated by its bioactive intermediate metabolite MPP+. Eldepryl could protect the neurotoxicity from MPTP. Chin Med J 2001; 114(3): 240-243

Objective To investigate the effects of free radicals (FRs) and amyloid β protein 1-40 (Aβ1-40) on the functions of expressed neurotransmitter receptors (NRs) in Xenopus oocytes. Methods Total RNA and messenger RNA(mRNA)was prepared from 3-month-old Wistar rat brain tissues with Promega kits and microinjected into maturated Xenopus oocytes(stages Ⅴ-Ⅵ)with 50 nl(50 ng)for each oocyte. The microinjected oocytes were incubated with modified Bath's solution at 19.0℃±1.0℃ for receptor expression and their currents were recorded with double electrode voltage clamp technique. Superoxide anion free radicals(SAFRs)were produced via a reaction system(HPX/XO)with hypoxanthine(HPX, 0.05 mol/L)and xanthine oxidase(XO, 0.1 U/L). In order to observe the effects of Aβ and SAFRs on the expressed glutamate receptor, HPX/XO and Aβ1-40 were added to incubation solution at 12 h, 24 h and 96 h before recording. Results The results showed that the oocytes expressed functional NRs originating from rat brain tissues. These NRs included muscarinic acetylcholine (mACh), glutamate (Glu), dopamine (DA), serotonin(5-HT) and y-aminobutyric acid (GABA). The current characteristics of expressed receptors were inward currents carried by chloride ion with their equibrilium potentials close to - 22 mV. The extent of effect on the current of expressed glutamate receptor from rat brain was different among different Aβ concentrations and incubation times. Aβ1-40 at a concentration of 20 nmol/L had little effect on the currents of expressed rat brain glutamate receptors up to 24 h of incubation period; but the currents of glutamate receptor were significantly decreased (25%off, P <0.01) in the treatment of 60 nmol/L Aβ1-40 over 24 h. Moreover,when 20 nmol/L Aβ1-40 was co-incubated over 12 h with SAFRs produced by the reaction system of HPX/XO, it was found that the currents of expressed rat brain glutamate receptors had been changed markedly. When the oocytes were co-treated with 60 nmol/L Aβ1-40 and SAFRs over a period of 12 h, the currents of glutamate receptor significantly decreased (21 %off, P <0 .05), and the decreased percentage reached 52%over 24 h co-treatment with 60 nmol/L Aβ1-40 and SAFRs. In addition, vitamin E had a partial effect against this inhibitory effect. Conclusion The results suggest that Aβ has a kind of inhibitory effect upon the current of the glutamate receptor, similar to the effects of free radicals. The effects can be antagonized by vitamin E. These imply that Aβ may play a role via inhibiting receptor function in the pathophysiology of Alzheimer's disease. Chin Med J 2001; 114(3): 244-247

Objective To test the hypothesis that neuronal cdc2-like kinase (Cdk5/p35nck5a) plays an important role in neuronal maturation and sprouting. Methods Changes kinase activity, expression levels and subcellular localizations of Cdk5 and p35nck5a in the rat hippocampus were studied during kindling progression by Western blot analysis,immunohistochemitry, immunoprecipitation and kinase assay. Results Kinase activity in kindling rats was significantly higher than that in normal adult rats. The kinase activity at stage 3 was most prominent among all stages of kindling progression. The changes in kinase activity coincided with those of p35nck5a expression in kindling rats. In contrast, the expression of Cdk5 was constant throughout the progression of kindling stages. However, subcellular localization of Cdk5dramatically changed in the hippocampal neurons of kindling rats. Cdk5 was translocated from axon to soma when kinase activity was high. p35nck5a was always localized in the soma throughout kindling progression. Conclusions Neuronal cdc2-like kinase plays an important role in synaptic reorganization, and the translocation of Cdk5 to the soma from the axon may be a novel regulatory mechanism to control kinase activity. Chin Med J 2001; 114(3): 248-252

Objective To investigate what effects BmKAS-1 (a polypeptide purified from the Chinese scorpion Buthus martensi Karsch [BmK] and named as BmK activator of skeletal-muscle ryanodine receptor) and its upstream mixture BmK1 -3-2 have on Na+ channels in dorsal root ganglion (DRG) small diameter neurons. Methods The whole-cell patch-clamp technique was used to investigate the effects of BmKAS-1 and BmK1 -3-2 on Na+ current in rat small diameter DRG neurons. Results About 50%peak Na+ current was suppressed by 10 μg/ml of BmK1 -3-2. 1.62 μg/ml of BmKAS-1 also blocked 50%peak Na+ current, and there was an obvious dose-dependent relationship. Conclusion Both BmK1 -3-2 and BmKAS-1 have a blocking effect on Na+ channels, and this may one of the mechanisms for the analgetic effect of BmK1 -3-2 and BmKAS-1. Chin Med J 2001; 114 (3): 253-256

Objective To evaluate the safety and efficacy of antegrade selective cerebral perfusion (ASCP) during aortic arch surgery as a means of extending the safe period of systemic circulatory arrest using multimodality neuromonitoring to objectively quantify the physiologic responses. Methods In twenty-two patients (all less than age 60) scheduled for repair of an aortic arch aneurysm,preoperative verification of effective collateral perfusion through both the carotid and vertebrobasilar arterial systems was documented with transcranial Doppler ultrasonography (TCD) . During cardiopulmonary bypass, the sole arterial inflow from the pump was via the right subclavian artery. The magnitude of ASCP was quantified by TCD using peak middle cerebral artery velocity, while flow adequacy was measured by continuous regional cerebrovenous oxygen saturation (rSO2) using dual-wavelength spatially resolved near-infrared spectroscopy. Results All patients experienced an uneventful recovery. Flow in the middle cerebral artery became undetectable at ASCP < 5 ml·kg-1·min-1, so adjustments from a 15-20 ml·kg-1•min-1 baseline were used to maintain rSO2 above 50%. Furthermore, ASCP flow was highly correlated (P <0.01) with both peak middle cerebral artery velocity and rSO2(r=0.86 and 0. 96, respectively). Conclusion Neuromonitoring guided ASCP may be expected to extend the safe period and is at least partly responsible for the absence of neurologic complications in this patient cohort. Chin Med J 2001; 114(3): 257-261

Objective To observe the immediate angiographic and intravascular ultrasound (IVUS) results and their effects on one month clinical outcomes in forty-one patients who submitted to coronary stent deployment with IVUS guidance. Methods All patients were allocated to coronary stent implantation with high inflation pressure. After good angiographic results (<20%residual stenosis), all patients underwent IVUS and higher-pressure dilatation would be necessary if criteria for optimal coronary stent implantation were not met. The optimal criterion of IVUS for stent implantation was the ratio of intrastent lumen cross-sectional area to the average of the proximal and distal reference lumen cross-sectional areas ≥80%. All patients had aspirin and ticlopidine therapy on the day of angioplasty and during the one month follow-up period. Results Optimal criteria of IVUS were obtained without any further intrastent dilatation in twenty-five patients but intrastent higher-pressure dilatation was performed in fourteen patients whose ultrasound results did not reach the criteria. In these patients, we increased the minimal intrastent lumen area 25.7%(P<0.05). Thirty-five patients (90%) had good minimal intrastent lumen area of IVUS. There were no deaths, myocardial infarction, acute stent thrombosis or need for revascularization during the study and the one month follow-up. Conclusions Intracoronary stent deployment under IVUS guidance, including combining aspirin and ticlopidine therapy, had beneficial ultrasound results and good clinical outcomes after one month follow-up. Chin Med J 2001; 114 (3): 262-265

Objective To investigate the association between gene polymorphism of the plasminogen activator inhibitor-1 (PAI-1) and myocardial infarction (MI) in Chinese. Methods PAI-1 genotyping with polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and allele specific polymerase chain reaction (ASPCR) was performed in 87 myocardial infarction patients and 92 unrelated healthy controls. All subjects' clinical features and PAI-1 activity were tested. Results There were two polymorphisms within the promoter, a G/A single base substitution polymorphism upstream at - 844 bp, and a single guanosine deletion/insertion 4G/5G polymorphism - 675 bp upstream from the start of transcription. Significant differences between the patients and the controls were observed neither for the frequencies of the GG, GA and AA genotypes nor for the PAI-1 activities of these three types. But for the 4G/5G polymorphism, there were significant differences between patients and controls for the frequencies of the 4G/4G, 4G/5G and 5G/5G genotypes (P <0.05) . In the MI group, the PAI-1activity of the 4G/4G type was significantly higher than that of the 5G/5G type (P <0.05). Further more,a positive correlation between the glucose level and PAI-1 activity was found (r=0.34, P=0.02). Conclusion This study indicates that the 4G/5G gene polymorphism of PAI-1 is associated with myocardial infarction, that 4G/4G type is probably an important hereditary risk factor, and that glucose has functional importance in regulating PAI-1 activity. Chin Med J 2001; 114(3): 266-269

Objective To investigate mechanisms of anti-hypertension and anti-cardiovascular remodeling by phenylalanine (phe) in spontaneously hypertensive rats (SHRs). Methods The comparison of blood pressure (BP) increment with the ages and cardiovascular changes of SHRs was made between the 3%phe-intervented group (SHR-phe) and the control SHRs group. Detection of the structural changes with the VIDAS digital vedio-frequency processing technique and light and electron microscopy were made. The cell growth and proliferation of cultured smooth muscle cells(CSMCs) of the thoracic aortas or myocardial fibroblasts were evaluated by measuring the 3H-thymidine counts per minute (cpm) incorporated into the new synthesized desoxyribonucleic acid (DNA) and determining the cell number with the crystal violet stain technique. The Ca2+ influx was measured in counts/min of 45CaCl2 after incubating it with 5 different concentrations of phenylalanine and the intracellular[Ca2+]i by Fura-Ⅱ/Am indicator. The total messenger ribonucleic acid (mRNA) of the myocardium was extracted and Northern blot analysis was performed with the probe collagen α2 (I) cDNA. The tyrosine hydroxylase (TH) activity was measured by high-performance liquid chromatography (HPLC) with electrochemical detector after having reacted with its substrate tyrosine and other reagents. The catecholamine contents in brain homogenat were detected by HPLC method. The comparison of pharmacokinetics of phenylalanine among SHR-phe, SHRs and control Wistar Kyoto (WKY) rats was made after intravenous injection of 3H-L-phe (1 ml/kg) by PK-GRAPH Program for kinetic calculation. The 3H-L-phe uptake by CSMCs after incubating for difinite intervals was also detected and compared. Results Phenylalanine could prevent the increase of BP with ages and the heart weight (heart/body weight index). The aortic media thickness and the collagen content in the myocardium were decreased significantly in SHR-phe. Whereas the dearranged cardiovascular structure was much improved. The mechanisms might be direct and specific inhibition of the DNA synthesis and proliferation of cardiovascular cells which may be related to the inhibition of collagen α2(I)cDNA, c-fos and c-myc expression. Other mechanisms may include decrease of intracellular [Ca2+]i and an inhibition of central sympathetic activity due to the results of higher TH activity in the caudate nucleus and higher adrenaline content in the posterior hypothalamus. Besides, partial recovery of phenylalanine metabolic aberrants existed in SHRs seems to be another possibility for its effectiveness. Conclusions Phenylalanine intervention could exert a definite anti-hypertension and anti-cardiovascular remodeling effects on SHRs like seen in human essential hypertension. Its mechanisms might be related to direct inhibition of growth in the cardiovascular cells, decrease of central sympathetic activity, the reverse of the exhibited phenylalanine metabolic aberrants in SHRs, and a decrement of intracellular [Ca2+]i. Chin Med J 2001; 114(3): 270-274

Objective To evaluate the relationship between plasma apoA-Ⅳ levels and coronary atherosclerosis and to explore its relation to other risk factors. Methods Using ELISA techniques, plasma apoA-Ⅳ levels were quantified in 181 patients who underwent coronary angiography (CAG). Patients were divided according to their coronary status into a coronary heart disease (CHD) group (stenotic lesion on CAG, n=118) and a control group (normal CAG, n=63). The severity of atherosclerosis was assessed by stenosis scoring of the different lesions. Other parameters,including apoA-Ⅰ apoB, Lp (a), HDL-C, LDL-C, TG, and TC, were measured as well. Univariate,logistic regression analyses were used to define the relationship between coronary atherosclerosis and plasma apoA-Ⅳ levels. Results When compared with the control group, plasma apoA-Ⅳ levels were found to be lower in the CHD group. There was a weak negative correlation between plasma apoA-Ⅳ levels and the severity of coronary atherosclerosis. ApoA-Ⅳ was found to be a relatively independent risk factor for CHD. We also found a positive correlation between apoA-Ⅳ and triglyceride levels. Conclusions ApoA-Ⅳ may be important in the prediction of CHD and coronary atherosclerosis severity. It may also play an important role in the metabolism of triglycerides. Chin Med J 2001; 114(3): 275-279

Objective To study the clinicopathologic features of hepatic angiomyolipoma (AML) and to investigate the feasibility of a new antibody-A103 as a diagnostic aid for AML. Methods Ten cases of AML were retrieved from hospital records and analyzed morphologically. Immunohistochemistry was performed on paraffin-embedded tissues with a panel of antibodies, including antibody-A103. Results There were eight women and two men, with ages ranging from 38 - 58 years (median 45.7). Clinically, nine cases were asymptomatic and found by imaging techniques. None of the patients had associated tuberous sclerosis. All tumors were sharply demarcated from the surrounding liver parenchyma. Histologically they were composed of a heterogeneous mixture of three components: thick-walled blood vessels, spindle or epithelioid smooth muscle cells and adipose tissue. All tumors showed a strong immunoreactivity to A103, HMB-45 and smooth muscle actins. Follow-up information on all 10 cases showed a benign course with no signs of recurrence. Conclusions Hepatic AML is a rare mesenchymal tumor of the liver. A103 is a promising marker for a pathologic diagnosis of hepatic AML. Chin Med J 2001; 114 (3): 280-285

Purpose To summarize the current strategies for the treatment of early and late Parkinson's disease(PD). Data sources The presented guidelines are based on the review of the literature as well as the author's extensive experience with the treatment of 7000 patients with PD over the past 25 years. Results An analysis of reported data as well as personal experience suggest that while young patients seem to have a slower progression of the disease, they are at a higher risk for developing levodopa induced complications, such as motor fluctuations and dyskinesias. It is, therefore, prudent practice to delay levodopa therapy, particularly in younger patients, until the PD symptoms become troublesome and interfere with social or occupational functioning. Other strategies, such as the use of deprenyl,amantadine, trihexyphenidyl and dopamine agonists, should be employed before instituting levodopa therapy. Entacopone and dopamine agonists are useful in smoothing out levodopa related motor fluctuations. Surgical interventions, such as pallidotomy and pallidal or subthalamic deep brain stimulation,are effective therapeutic strategies, but should be reserved only for patients in whom optimal medical therapy fails to provide satisfactory control of symptoms. Conclusion The medical and surgical treatment of patients with PD must be individualized and tailored to the needs of the individual patient. Chin Med J 2001; 114(3): 227-234

Purpose To review recent knowledge on the clinical features, pathology and pathophysiology, diagnosis and treatment of Miller Fisher syndrome (MFS). Data sources Clinical and laboratory studies on MFS in the past 10 years were included. Results A viral infection preceded neurological symptoms in 71.8%of MFS patients. Typical MFS consists of the triad of ataxia, areflexia and ophthalmoplegia. Other cranial nerves are also involved, which may overlap with limb weakness in typical Guillain-Barre syndrome (GBS). Lower cranial nerve variants of GBS, atypical MFS and ataxic neuropathies may overlap, and are thought of as variant forms of MFS. Recurrence and CNS involvement is found more frequently in MFS than in GBS. Antibody to GQ1b, a tetrasyaloganglioside (GQ1b antibody) which is found in close relation to ophthalmoplegia in MFS, is also associated with Campylobacter jejuni (C. jejuni) serotype Penner 2. This suggests that C. jejuni may induce MFS via the GQ1b structure. The GQ1b antibody may lead to the failure of acetylcholine release from motor nerve terminals, which has been confirmed by clinical neurophysiological results. Conclusions Many studies have shown similarities in the pathogenesis of MFS and GBS. However, there are still some differences between them, especially in the areas of sensory and CNS involvement. The GQ1b antibody is thought of as one of the key factors in the pathogenesis of MFS, especially with ophthalmoplegia, and it may prove a useful clinical marker in the diagnosis of MFS. Chin Med J 2001; 114 (3): 235-239

Objective To investigate the changes on protein kinase C (PKC) activity of alveolar macrophages (AMs)in patients with idiopathic pulmonary fibrosis (IPF). Methods The PKC activity of AM in 9 healthy volunteers and 15 patients with IPF was investigated by measuring the radioactivity. Results The total, cytosolic and membrane PKC activity of AM in bronchoalveolar lavage fluid(BALF)from patients with IPF were higher than those from control group(P<0.01, P<0.05 and P<0.05, respectively). The total and the membrane-associated PKC activity had a positive correlation with the number of cells in BALF(r=0.8135, P<0.01 and r=0.5917, P<0.05), respectively. Conclusion As a bypass of transmembrane signal transduction, PKC was suggested to be involved in the origination and development of IPF. Chin Med J 2001; 114(3): 321-323