心钠素对心肌血管钙超载的影响

提要本研究是在大鼠VD_3+Nicotine引起的心血管钙超载模型上观察心钠素(ANF)治疗(10ug ·kg~-1/d),对钙超载的影响。结果发现,钙超载组动物主动脉、心肌组织钙含量较对照组分别增高24倍(54.4±2.2vs 2.3±0.04fumol/gww)和9倍(16.9±2.1vs1.8±0.1umol/gww)。ANF治疗能显著抑制钙超载的发生,主动脉和心肌组织钙含量较钙超载组分别降低92％(3.8±0.4 umol/gww)和66％(5.6±0.6umol/gww)。离体滋流的钙超载血管环较对照组对去甲肾上腺素收缩反应增强;对乙酰胆碱舒张反应减弱,对硝普钠舒张反应无影响。ANF能显著改善钙超载所致的血管反应性障碍。实验结果表明,ANF具有显著的防治心血管钙超载的作用。     

维生素D_3与心肌细胞电活动关系的实验研究

本实验利用标准玻璃微电极技术和微机系统的实时应用,在离体豚鼠右心室乳头肌上观察维生素D_3对其细胞电活动的影响。结果表明维生素D_3可使心肌细胞动作电位和零相最大去极化速率发生明显改变,其变化主要是由于通过细胞膜慢通道有大量的Ca~(2+)内流,使细胞内Ca~(2+)超负荷来实现的。     

异搏定区域动脉灌注在阻止急性胰腺炎重症化治疗中的作用

目的探讨钙拮抗剂异搏定区域动脉灌注在阻止急性胰腺炎重症化治疗中的作用。方法45例轻型急性胰腺炎患者被随机分为3组常规治疗组、静脉治疗组及动脉灌注组。入院后,常规治疗组采取常规保守治疗;静脉治疗组行合理液体治疗,静脉注射异搏定;动脉灌注组液体补充同时采用持续动脉灌注异搏定1~2周。测定治疗后1、4及7d血清肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、黏附分子-1(ICAM-1)及P-选择素(P-selectin)水平。结果治疗后4、7d,血清TNF-α和P-selectin水平动脉灌注组较静脉治疗组及常规治疗组明显降低(P<0.05);血清IL-1β水平动脉灌注组和静脉治疗组均较常规治疗组明显降低(P<0.05);血清ICAM-1水平动脉灌注组明显低于常规治疗组(P<0.05)。结论持续区域动脉灌注异搏定可能通过减少细胞因子的产生,抑制黏附分子P-selectin和ICAM-1的上调,阻止急性胰腺炎重症化发展。     

HFE codon 63/282 (H63D/C282Y) dimorphism in German patients with genetic hemochromatosis

Abstract: Genetic hemochromatosis (GH) is closely associated with genes of the major histocompatibility complex (MHC) on chromosome 6. Recently, a candidate gene for GH, with structural similarities to MHC class I genes, designated HLA-H and presently named HFE, has been cloned. The HFE gene is localized telomeric to the MHC and several reports have indicated that the HFE gene is mutated in GH patients. In the present study we have analyzed the relationship of HFE gene variants and disease manifestation in GH patients and family members. Fifty-seven patients with GH, 73 family members and 153 healthy blood donors were studied for the amino acid dimorphism at codon 63 (His63Asp=H63D) and codon 282 (Cys282Tyr= C282Y) of the HFE gene. The codon 63 and 282 dimorphism were defined by PCR amplification of genomic DNA samples and restriction enzyme digestion using RsaI/SnaBI for C282Y and Bcll/Mbo 1 for H63D. Ferritin, transferrin serum levels and total iron-binding capacity were determined prior to therapeutic intervention. The Tyr-282 substitution occurred in 53 (93%) of patients compared with 8 (5.2%) of controls (OR=169, P >0.0001). Fifty-one (90%) patients were Tyr-282 homozygous. In contrast, the Asp-63 substitution was present in 5 (8.8%) of the patients compared with 34 (22%) of controls (OR=0.39, P =NS) with none of the patients being homozygous. In Tyr-282 homozygous GH patients serum ferritin levels, transferrin saturation, liver iron and liver iron index were elevated significantly compared to Tyr-282-negative patients, whereas no difference was observed between Tyr/Cys-282 heterozygous and Tyr-282-negative patients.     

Correlation between soluble transferrin receptor and serum ferritin levels following bone marrow transplantation for thalassemia

Abstract: This study analyzes the serum transferrin receptor (sTfR) levels in a series of 230 ex-thalassemics with a follow-up of 1 to 9 years after bone marrow transplantation (BMT) for homozygous β thalassemia. Ex-thalassemics are individuals, cured of homozygous β thalassemia by BMT, who maintain different degrees of iron overload acquired during the pretransplant period. Both in experimental and clinical conditions, sTfR concentrations have been shown to be a quantitative measure of body iron status. This study was carried out to assess whether the level of sTfR may be of help in determining the extent of iron overload in ex-thalassemics. Patients who received the marrow from their HLA-identical sibling donor heterozygous for β thalassemia, namely heterozygous ex-thalassemics, displayed significantly higher levels of sTfR than patients transplanted from their normal sibling donors (normal ex-thalassemics). This finding suggests that increased erythropoiesis, albeit in part ineffective in heterozygous ex-thalassemics, is responsible for the sTfR increment. Both heterozygous and normal ex-thalassemics had significant lower sTfR levels than their heterozygous (p < 0.003) or normal (p < 0.0001) donors, respectively. These differences may be ascribed to the presence of iron overload in ex-thalassemics in comparison to their normal or heterozygous donors who did not present excess of iron in the body. A significant inverse correlation between sTfR and serum ferritin levels (r = –0.54, p < 0.0001) was found when normal ex-thalassemics were considered. In heterozygous ex-thalassemics, the lack of correlation between these two parameters may be explained by the enhanced erythropoietic activity of individuals with thalassemic trait. These results suggest that the level of sTfR may be a useful indicator of iron overload in normal ex-thalassemics.     

Enhanced Fluid Removal Guided by Blood Volume Monitoring During Chronic Hemodialysis

Fluid overload predisposes chronic hemodialysis patients to cardiovascular disease, a significant cause of morbidity and mortality in these patients. We evaluated the efficacy of monitoring changes in blood volume during routine hemodialysis to detect fluid overload. Intradialytic changes in blood volume were monitored by continuously measuring hematocrit in all 56 patients in a single dialysis unit over 7 weeks. After Week 1, patients were categorized into 2 separate groups depending on their maximum intradialytic decreases in blood volume. In Group 1, 46 of 56 or 82% had greater than a 5% decrease in blood volume while in Group 2, 10 of 56 or 18% had less than a 5% decrease in blood volume. During Weeks 2–7, dialytic fluid removal was intentionally increased in Group 2 patients by 0.80 ± 0.62 L (mean ± SD) or 47 ± 43%. This intervention resulted in a larger (p < 0.02) intradialytic decrease in body weight (2.7 ± 0.9 kg versus 2.0 ± 0.8 kg) and a larger (p < 0.02) intradialytic decrease in blood volume (15 ± 5% versus 4 ± 1%) than experienced during Week 1 with a low incidence of symptoms. We conclude that there is a significant percentage of chronic hemodialysis patients who can tolerate additional fluid removal without hypovolemic symptoms even though they are considered to be at dry weight by routine physical examination and that the identification of these patients can be facilitated by intradialytic blood volume monitoring.     

The regional distribution of adenosine-regulating enzymes in the left and right ventricle walls of control and hypertrophic heart

Summary The transmural distribution of the adenosine-generating enzyme 5-nucleotidase (5N) and of the adenosine-degrading enzymes adenosine deaminase (ADA), AMP deaminase (AMP-D) and adenosine kinase (Ado-K) were determined across the walls of left and right ventricles of control and hypertrophic rat hearts.The enzyme distribution across the left ventricle wall (but not across the right wall) of normal hearts was not uniform: 5N activity shows its highest levels in the subepicardial and in the subendocardial regions, whereas all the other enzyme activities show their lowest levels. A similar pattern of transmural distribution was also detected in other mammalian species (ox and pig).In the experimental cardiac hypertrophy, caused by two different types of chronic cardiac overload, the levels and the profiles of transmural distribution of 5N and ADA enzyme activities may significantly change across the rat left ventricle wall.     

压力超负荷大鼠心、肺、肾血管重构的动态研究

目的 探讨压力超负荷与大鼠心、肺、肾内小动脉形态学重建的关系。方法 采用缩窄腹主动脉造成大鼠压力负荷模型，将大鼠随机分为两组：假手术组（SOG)和手术组(OG)。每组分为术后1、2、4、7、14、21、30、45、60d 9个时间点，对大鼠心、肺、肾组织连续切片，采用光镜配合计算机图像分析技术检测三个脏器小动脉几何形态的动态改变。结果 (1)随着压力负荷的增加，心、肺、肾小动脉的形态学重建可能存在时间顺序。(2)平均动脉压和造模时间与小冠状动脉和肾小动脉的壁腔比显著相关，而对小冠状动脉的管壁面积无影响；收缩压和造模时间与肾小动脉的管壁面积显著相关；造模时间与肺小动脉的壁腔比和管壁面积显著相关。结论 压力超负荷与心、肺、肾小血管的动态重构关系密切。小冠状动脉的重建以中膜平滑肌细胞的重排为主，肺、肾内小动脉的重建则可能存在中膜平滑肌细胞的肥大和增殖。