2001年 · 第114卷第06期

Objective To investigate whether the interaction of hypertension and diabetes aggravates endothelial dysfunction and leads to smooth muscle dysfunction. Methods Noninvasive methods were used to the investigated patients with type 2 diabetes mellitus(2-DM) (Group 1), patients with hypertension (Group 2) and patients with both 2-DM and hypertension(Group 3), as well as a normal control group (Group 4) by studying a brachial artery without evidence of atherosclerotic plaque formation. Results Results showed that endothelium-dependent vasodilation decreased significantly in Group 1(5.74%±3.32%, P<0.05), Group 2 (4.14%±2.93%, P<0.01), and Group 3 (2.78%±2.08%,P <0.001) as compared to the control (9.45%±3.88%). The nitroglycerin-induced vasodilation (smooth muscle function) in Group 3 was significantly decreased as compared to the control group (14.11%±4.63%vs 23.53%± 6.77%, P <0.001), but there were no differences in nitroglycerin-induced vasodilation between Group 1, Group 2 and Group 4. On univariate analysis, a reduced vasodilator response to nitroglycerin was associated with endothelium-dependent vasodilation (r=0.54, P <0.001). Conclusion Our results indicate that the interaction of 2-DM and hypertension aggravates endothelial dysfunction and further impairs the smooth muscle function. Chin Med J 2001; 114(6): 563-567

Objectives To assess the preliminary clinical results of implantation of dual chamber pacemaker defibrillator and to evaluate the safety and effectiveness of placement of endocardial leads in the axillary vein. Methods Seven patients with ventricular tachycardia and/or ventricular fibrillation (VT/VF), associated with bradyarrhythmia received implantation of a dual chamber pacemaker defibrillator, including 5 patients with coronary artery disease and 2 patients with dilated cardiomyopathy. The atrial and ventricular leads were introduced via the axillary vein under venographic guidance. Results Dual chamber pacemaker defibrillators were successfully implanted in the left chest subcutaneous pocket in 5 patients and the left pectoral muscular pocket in 2 patients. All the VT/VF occurring either inducibly during the procedure or spontanuously during follow-up were detected promptly and treated successfully. Both the pacing and sensing functions were satisfactory. The endocardial leads required were successfully introduced via the axillary vein without major complications. Conclusion Dual chamber pacemaker defibrillators can provide reliable therapy for VT/VF and the dual chamber pacing function. Placement of endocardial leads via the axillary vein under venographic guidance is safe and effective. Chin Med J 2001; 114(6): 568-570

Objective To study the cellular mechanism of the effect of Ang Ⅱ on ICa, L in single guinea-pig ventricular cells by using losartan and 1 -(5-lsoquinolinylsulfonyl)-2-Methyl-Piperazine (H-7) as the Ang Ⅱ type 1receptor (AT1) inhibitor and protein kinase C inhibitor, respectively. Methods Patch clamp techniques were used to study the cellular mechanism of the effect of Ang Ⅱ on ICa, L in single guinea-pig ventricular cells. Results In the whole cell patch clamp recording model, Ang Ⅱ stimulated ICa, L in a concentration dependent manner; the maximal effect was obtained at 100 nmol/L (n=9) . At 30 nmol/L, Ang Ⅱstimulated peak ICa, L from 11.3 ± 0.6 pA/pF to 15.3 ± 0.6 pA/pF (at + 10 mV, n=9, P<0.05). 100nmol/L Losartan, a specific AT1, receptor inhibitor, had no effect on ICa,L(n=9), but the effect of Ang Ⅱon ICa,L was inhibited by 100 nmol/L Losartan. Ang Ⅱ on ICa,L was also inhibited by 20 μmol/L H-7, a specific protein kinase C inhibitor, whereas H-7 alone has no effect on ICa, L(n=9). Conclusion Ang Ⅱ stimulates ICa,L in guinea-pig ventricular cells by binding to AT1, through a transduction pathway involving protein kinase C. Chin Med J 2001; 114(6): 577-582

Objectives To assess the effect of an ACE inhibitor and an Ang Ⅱ type 1 (AT1) receptor antagonist on preventing hepatic fibrosis induced by CCI4 in rats and to investigate whether there is the expression of AT1receptors on hepatic stellate cells. Methods Studies were conducted in male Sprague-Dawley rats. Except for model group and control group, in three treated groups, either enalapril (5 mg/kg), or losartan (10 mg/kg), or enalapril+ losartan were given to the fibrotic rats (daily gavage). Saline vehicle was given to the control group. After 6 weeks,liver fibrosis was assessed directly by hepatic morphometric analysis. The expression of AT1 receptors andα-smooth muscle actin (α-SMA) in liver tissue and isolated hepatic stellate cells (HSC) were detected by immunohistochemical techniques. Results Compared with the fibrosis in rats of the model group, rats treated with either enalapril or losartan, or a combination of two drugs, showed a limited expansion of the interstitium (P <0.05), but no significant difference was observed among the three treated groups (P> 0.05). The expression of AT1receptors was found in abundance in the fibrotic interstitium of the fibrotic rats, whereas in the normal control rats they were limited to the vascular wall. AT1 receptors were also expressed on activated HSC in culture plates. Conclusions Angiotensin-converting enzyme inhibitors and AT1 blockers might slow the progression of hepatic fibrosis. Activated HSCs expressed AT1 receptors. Activation of RAS might be related to hepatic fibrogenesis induced by CCI4. Chin Med J 2001; 114(6): 583-587

Objective To further define the extent of chromosome 9p21 deletion in periampullary neoplasms. Methods The loss of heterozygosity at 5 microsatellite polymorphic markers on chromosome 9p21 was detected by polymerase chain reaction (PCR), polyacrylamide gel electrophoresis (PAGE) and silver staining in 35 specimens of periampullary neoplasms and their matching blood samples. Results Fifty percent (4/8) of pancreatic cancer cases showed the loss of heterozygosity at one or more microsatellite loci, with the more frequent sites of D9S974 (37.5%) and D9S942 (28.6%). and some showing consecutive allelic loss. Sixty-two point five percent (5/8) of ampullary carcinoma cases showed loss of heterozygosity at one or more of the loci, frequent site of loss being D9S942 (42.9%) and the next most frequent being IFNA (37.5%) and D9S171 (37.5%). Loss of one locus was observed in 14.2%(1/7) of insulinoma. Conclusion The minimal common region of chromosome deletion in periampullary neoplasms is defined between the D9S974 and D9S942 loci within a 15 kb interval in 9p21, suggesting the involvement of a novel tumor suppressor gene in their carcinogenesis. Chin Med J 2001; 114(6): 588-591

Objective To observe the short-term and long-term effects of leptin on hepatic glucose oxidation and glucokinase gene expression. Methods Rat hepatic cell line BRL was incubated with leptin of different doses (range from 10 ng/ml - 200ng/ml) for 1 h or 24 h. Glucose oxidation was determined by liquid scintillation counting. Glucokinase gene expression (corrected by β-actin) was determined by reverse transcription semi-quantitative polymerase chain reaction. Results Treatment with leptin 10 ng/ml for 1 h had no significant effects on glucose oxidation in hepatic cells. However, at the doses ranging from 50 ng/ml to 200 ng/ml, leptin significantly inhibited glucose oxidation. These effects disappeared when the hepatic cells were exposed to leptin for 24 h. Glucokinase mRNA expression was reduced significantly after both 1 h and 24 h exposure to leptin (100 ng/ml) as compared to that of the control group. Conclusion A low dose of leptin has no significant effect on glucose oxidation in hepatic cells. A relatively high dose of leptin has an acute inhibitory effect on the glucose oxidation in hepatic cells. This effect may likely involve the inhibition of glucokinase gene expression. The inhibitory effect on glucose oxidation is transient and disappears with prolonged exposure time. Chin Med J 2001; 114(6): 592-595

Objective To gain a better understanding of the regulatory mechanism and kinetic behaviour of granulocyte colony-stimulating factor (G-CSF). Methods An enzyme-linked immunosorbent assay (ELISA) method was used to detect serum G-CSF in 61 patients with chronic renal failure ± long-term hemodialysis and 30 normal controls. Results Serum G-CSF levels in CRF patients were significantly higher than in normal controls. Eighty percent of patients had detectable G-CSF and serum G-CSF levels were 566.40 ±207.98 ng/L in non-hemodialyzed (non-HD) patients. The detectable percentage in hemodialyzed patients was 93.33%. serum G-CSF levels in pre-HD and post-HD patients were 1255.36±611.25 ng/L and 1151 .61±599.47ng/L respectively. Serum G-CSF levels in HD patients were slightly higher than in non-HD patients, but no significant difference was found between the two groups. No difference was found between the G-CSF values obtained in pre-HD and post-HD patients. There was no relationship between G-CSF levels and WBC, BUN or Scr(P> 0.05). Conclusion The high value of G-CSF in patients with CRF may be caused by a decrease in G-CSF clearance and/or an increase in G-CSF release. Chin Med J 2001; 114(6): 596-599

Objective To observe in vitro effects and morphological changes of human peripheral blood dendritic cells(DCs) on the ability of lymphokine and phytohaemagglutininum (PHA) activated killer (LPAK) cells to induce apoptosis of the human hepatoma cell line (BEL-7402, B). Methods Experimental groups were divided into LD group (DCs + L + B), L group (L + B), D group(DCs + B) and B group. The methods of neutral red uptake, ordinary light microscopy, electron microscopy, TDT mediated X-dUTP nick end labeling (TUNEL) were used. Results The difference between the D group and the B group was not distinct (P>0.05). The difference between the LD group and the L group was distinct, with DCs + LPAK > LPAK (P <0.01) in cytotoxity. Apoptotic cells were TUNEL positive in light microscopy, and apoptotic nuclei were stained yellow brown and dark brown, with size and shape varying from cell to cell. Ultrastructural change in apoptotic tumor cells comprised of compaction and condensation of nuclear chromatin, and condensation of cytoplasm and apoptotic bodies. At the same time, LPAK cells manifested the characteristics of autophagic apoptosis, and there were some autophagic bodies in it. Conclusions The combination of human blood DCs and LPAK cells could induce apoptosis of BEL-7402cells effectively, with some LPAK cells manifesting the characteristics of autophagic apoptosis. Chin Med J 2001; 114 (6): 600-605

Objective To study the transcription effects and cleavage activities of rat caspase-3 specific hammerhead ribozyme (Rz107) in both cell-free conditions and BRL-3A cells. Methods Rat caspase-3 gene fragment was cloned into the pGEM-T EASY vector under the T7 promoter control. The 32P-labeled caspase-3 transcript was the target-RNA. Rz107 genes designed against caspase-3 mRNA were cloned into vector p1.5 between 5'-cis-Rz and 3’-cis-Rz. 32P-labeled ribozyme transcripts were incubated with target-RNAs at different conditions and autoradiographed after denaturing gel-electrophoresis. Rz107 was electroporated into BRL-3A cells and the Rz107 expression was analyzed by RT-PCR. Results In cell-free conditions, Rz107 was active at 37℃. The optimal temperature was 50℃. The Km and kcat were 14.13 nmol/L and 2.31 • min-1 respectively. Intracellular cleavage efficiency of Rz107 was 37%, as analyzed by RT-PCR. This indicated that the design of Rz107 was correct, and Rz107 had the activity of common enzymes. Conclusions Rz107 in cell-free conditions possessed perfect specific catalytic cleavage activity, and it can also cleave the target RNA successfully in cells. The results illustrate the feasibility of ribozyme therapy as a potential alternative approach for treating liver disease caused by apoptosis. Chin Med J 2001; 114(6): 606-611

Objectives To provide modern surgical management of complex intracranial aneurysms and to evaluate its clinical outcome. Methods Direct microsurgical repair of complex intracranial aneurysms was performed in 42 patients. Glasgow outcome scale (GOS) was used to evaluate surgical outcome. Results Aneurysms were clipped in 37 patients, trapped in 3, and wrapped in 1. Proximal parent artery was occluded in 1 patient. At the time of hospital discharge, good outcomes(GOS scores of 4 or 5) were achieved in 37 patients, poor outcomes (GOS scores of 2 or 3) in 3, and death in 2. A total of 29 patients were followed up for 4 months to 7 years;good outcome was achieved in 27 patients, poor outcome in 1, and death in 1. Conclusions Surgical intervention of complex intracranial aneurysms is still difficult. Multiple surgical techniques such as wide exposure, temporary occlusion of parent arteries, brain protection, decompression of aneurysms, shrinkage of wide aneurysmal neck, aneurysmorrhaphy and vessel plastic should be taken to get good outcome. In the future, surgical treatment of complex intracranial aneurysms, combined operative and endovascular techniques in a complementary way is useful for a better prognosis.

Objective To analyze the results of 18 patients with giant aneurysms of anterior circulation retrospectively. Methods In the patients who had been surgically treated, direct clipping of the aneurysm was accomplished in 11patients, aneurysm trapping or removal after trapping in 4,aneurysm excision or trapping with parent artery anastomosis in 2, and aneurysm wrapping in 1. Results Early postoperative neurological function was evaluated according to Glasgow Outcome Scale. The 11patients having direct clipping of the aneurysm and 2patients receiving aneurysm excision or trapping with parent artery anastomosis gained good recovery except one who had preoperative IV grade according to Hunt and Hess grades after SAH and had severe disability postoperatively. In 4patients with aneurysm trapping or excision after trapping,one experienced temporary contralateral hemiparesis, and another patient had hemorrhage in the operative field and recovered smoothly after a second operation for hematoma. One patient with aneurysm wrapping died from postoperative aneurysm rebleeding. Conclusions Direct clipping is preferred for giant intracranial aneurysm, Unclippable aneurysm require alternative methods that compromise parent arteries and need revascularization to restore sufficient cerebral blood flow.