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Distribution of iodine 125-labeled alpha1-microglobulin in rats after intravenous injection. 碘125标记α - 1微球蛋白在大鼠静脉注射后的分布。
Pub Date : 2001-03-01 DOI: 10.1067/MLC.2001.112957
Jörgen Larsson, K. Wingårdh, T. Berggård, Julia R. Davies, Lennart Lögdberg, Sven-Erik Strand, Bo Åkerström
The 28-kd plasma protein alpha(1)-microglobulin is found in the blood of mammals and fish in a free, monomeric form and as high-molecular-weight complexes with molecular masses above 200 kd. In this study, iodine 125-labeled free and high-molecular weight rat alpha(1)-microglobulin (a mixture of alpha(1)-microglobulin/alpha(1)-inhibitor-3 and alpha(1)-microglobulin/fibronectin complexes) were injected intravenously into rats. The distribution of the proteins was measured by using scintillation camera imaging. Both forms of (125)I-labeled alpha(1)-microglobulin were rapidly cleared from the blood, with a half-life of 2 and 16 minutes for the initial and late phase, respectively, for free alpha(1)-microglobulin; and a half-life of 3 and 130 minutes for the initial and late phase, respectively, for the complexes. After 45 minutes, 6%, 16%, 27%, 13%, and 34% of the free (125)I-labeled alpha(1)-microglobulin and 18%, 21%, 6%, 10%, and 42% of the (125)I-labeled alpha(1)-microglobulin complexes were found in the blood, gastrointestinal tract, kidneys, liver, and the remainder of the body, respectively. The local distribution of injected (125)I-labeled alpha(1)-microglobulin in intestines and kidneys was investigated by microscopy and autoradiography. In the intestine, both forms were distributed in the basal layers, villi, and luminal contents. The results also suggested intracellular labeling of epithelial cells. Well-defined local regions containing higher concentrations of injected protein could be seen in the intestine. In the kidneys, both forms were found mostly in the cortex. Free (125)I-labeled alpha(1)-microglobulin was found predominantly in epithelial cells of a subset of the tubules, whereas the (125)I-labeled complexes were more evenly distributed. Intracellular labeling was indicated for both alpha(1)-microglobulin forms. The results thus indicate a rapid transport of (125)I-labeled alpha(1)-microglobulin from the blood to most tissues.
28kd血浆蛋白α(1)-微球蛋白以游离单体形式存在于哺乳动物和鱼类的血液中,并以分子量大于200kd的高分子量复合物形式存在。本研究将碘125标记的游离高分子量大鼠α(1)-微球蛋白(α(1)-微球蛋白/ α(1)-抑制剂-3和α(1)-微球蛋白/纤连蛋白复合物的混合物)静脉注射到大鼠体内。利用闪烁照相机成像技术测量了蛋白质的分布。两种形式的(125)i标记α(1)-微球蛋白都能迅速从血液中清除,游离α(1)-微球蛋白的初始和晚期半衰期分别为2分钟和16分钟;复合物的初始和晚期的半衰期分别为3分钟和130分钟。45分钟后,在血液、胃肠道、肾脏、肝脏和身体其他部位分别发现6%、16%、27%、13%和34%的游离(125)i标记α(1)微球蛋白和18%、21%、6%、10%和42%的(125)i标记α(1)微球蛋白复合物。用显微镜和放射自显影技术观察注射(125)i标记α(1)-微球蛋白在肠道和肾脏的局部分布。在肠道中,两种形式均分布于基底层、绒毛和管腔内容物中。结果还提示上皮细胞的胞内标记。在肠道中可以看到含有高浓度注射蛋白的明确的局部区域。在肾脏中,这两种形式主要在皮质中发现。游离(125)i标记的α(1)微球蛋白主要存在于小管子集的上皮细胞中,而(125)i标记的复合物分布更均匀。细胞内标记用于α(1)-微球蛋白两种形式。因此,结果表明(125)i标记α(1)-微球蛋白从血液快速运输到大多数组织。
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引用次数: 47
Adenovirus-mediated transfer of the atrial natriuretic peptide gene in rat pulmonary vascular smooth muscle cells leads to apoptosis. 腺病毒介导的心房利钠肽基因在大鼠肺血管平滑肌细胞中的转移导致细胞凋亡。
Pub Date : 2001-03-01 DOI: 10.1067/MLC.2001.112725
I. Déprez, M. Darmon, M. Hira, M. Adam, S. Sanquer, E. Teiger, V. Chetboul, M. Eloit, S. Adnot, I. Pham
Atrial natriuretic peptide (ANP) exhibits relaxant and growth-inhibiting effects on vascular smooth muscle cells (VSMCs). To obtain ANP gene expression in VSMCs, we built a recombinant adenovirus containing the ANP cDNA controlled by the adenovirus major late promotor (AdMLP-ANP). After pulmonary VSMC treatment with AdMLP-ANP at a multiplicity of infection ranging from 5 to 100 TCID(50)/cell, immunoreactive ANP was detectable in the cell culture medium at a level that reached 101 +/- 27 pmol/well after 2 days. The newly expressed ANP was biologically active, as evidenced by its ability to induce cyclic guanosine monophosphate accumulation in target cells and to mimic the effect of exogenous ANP (10(-8) to 10(-7) mol/L). Cell growth and survival of AdMLP-ANP-infected cells were decreased and were associated with the promotion of VSMC apoptosis. These effects, which occurred at a multiplicity of infection of 10 to 100 TCID(50)/cell, were observed neither in cells infected with the control adenoviral constructs (AdMLP-betaGAL and AdMLP-gD) nor in cells treated with exogenous ANP (10(-7) to 10(-6) mol/L). These results showing VSMC apoptosis in response to ANP gene expression may have important implications for the prevention of vascular remodeling by gene therapy.
心房利钠肽(ANP)对血管平滑肌细胞(VSMCs)具有松弛和抑制生长的作用。为了获得ANP基因在VSMCs中的表达,我们构建了由腺病毒主要晚期启动子(AdMLP-ANP)控制的含有ANP cDNA的重组腺病毒。AdMLP-ANP在5 ~ 100 TCID /细胞的感染倍数范围内治疗肺VSMC后,2天后在细胞培养基中检测到免疫反应性ANP,水平达到101 +/- 27 pmol/well。新表达的ANP具有生物活性,其能够诱导环鸟苷单磷酸在靶细胞中积累,并模仿外源性ANP(10(-8)至10(-7)mol/L)的作用。admlp - anp感染细胞的细胞生长和存活降低,并与VSMC凋亡的促进有关。这些效应发生在10至100 TCID(50)/细胞的多重感染下,在用对照腺病毒构建体(AdMLP-betaGAL和AdMLP-gD)感染的细胞和用外源性ANP(10(-7)至10(-6)mol/L)处理的细胞中都没有观察到。这些结果表明VSMC凋亡对ANP基因表达的响应可能对基因治疗预防血管重塑具有重要意义。
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引用次数: 3
Natural history of chronic hepatitis C: identifying a window of opportunity for intervention. 慢性丙型肝炎的自然史:确定干预的机会之窗。
Pub Date : 2001-03-01 DOI: 10.1016/S0011-5029(01)90006-9
Huy A. Nguyen, Samuel B. Ho
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引用次数: 4
Effect of erythromycin on matrix metalloproteinase-9 and cell migration. 红霉素对基质金属蛋白酶-9及细胞迁移的影响。
Pub Date : 2001-03-01 DOI: 10.1067/MLC.2001.112726
N. Hashimoto, T. Kawabe, T. Hara, K. Imaizumi, H. Wakayama, H. Saito, K. Shimokata, Y. Hasegawa
Erythromycin (EM) has an anti-inflammatory effect that may account for its clinical benefit in the treatment of chronic inflammatory diseases such as diffuse panbronchiolitis. To investigate the mechanism of this anti-inflammatory effect, we studied the relationship between the concentration of EM and matrix metalloproteinase-9 (MMP-9) activity, which is important in cell migration. We showed that EM suppressed the gelatinolytic activity of U937 cell-derived MMP-9 by using gelatin zymography, showed that expressions of MMP-9 protein and MMP-9 mRNA were down-regulated by EM in a dose-dependent manner, and showed that U937 migration was also suppressed by EM. We also demonstrated that EM treatment suppressed the gelatinolytic activity of MMP-9 in spleen macrophages. These findings suggest that the suppressive effect of EM on MMP-9 activity is one of the anti-inflammatory mechanisms that inhibit the migration of inflammatory cells into the inflammatory site.
红霉素(EM)具有抗炎作用,这可能是其治疗慢性炎症性疾病(如弥漫性泛细支气管炎)的临床益处的原因。为了探讨这种抗炎作用的机制,我们研究了EM浓度与基质金属蛋白酶-9 (MMP-9)活性的关系,MMP-9在细胞迁移中起重要作用。我们通过明胶酶谱法发现EM抑制了U937细胞源性MMP-9的溶胶活性,EM以剂量依赖的方式下调了MMP-9蛋白和MMP-9 mRNA的表达,EM也抑制了U937的迁移。我们还发现EM处理抑制了脾脏巨噬细胞中MMP-9的溶胶活性。这些发现提示,EM对MMP-9活性的抑制作用是抑制炎症细胞向炎症部位迁移的抗炎机制之一。
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引用次数: 38
Vascular endothelial growth factor in peritoneal dialysis: a longitudinal follow-up. 血管内皮生长因子在腹膜透析:纵向随访。
Pub Date : 2001-02-01 DOI: 10.1067/MLC.2001.112235
M. M. Zweers, D. Struijk, W. Smit, R. Krediet
In a previous study, vascular endothelial growth factor (VEGF) was found to be locally produced in the peritoneal tissue of patients undergoing peritoneal dialysis (PD) who were being treated with glucose-containing PD solutions. Locally produced VEGF (LVEGF) was positively related to the mass transfer area coefficient (MTAC) of creatinine and to glucose absorption, both of which are representative of the peritoneal vascular surface area. It was therefore hypothesized that VEGF is involved in the peritoneal neoangiogenesis found in long-term PD. The aim of the present study was to investigate the time course of peritoneal VEGF levels in PD patients treated with glucose-based PD solutions during longitudinal follow-up. We also studied the effect of the switch to glucose-free PD treatment on VEGF production. Forty standard peritoneal permeability analyses (SPAs) with 3.86% glucose-containing dialysis solution were investigated. The SPAs were performed in 10 PD patients with a median number of three SPAs per patient during a follow-up of 23 months. Duration of PD treatment at the last SPA was 74 months. All patients were initially treated with glucose-containing dialysis solutions. Four patients switched after 114 months of glucose-based PD to glucose-free PD and were followed for 7 months. A PD regimen of icodextrin, glycerol, and amino acid-based dialysis solutions was applied in these patients. Four SPAs were performed per patient in this period. To predict the VEGF dialysate-to-serum ratio (D/S), when diffusion would be the only explanation for the VEGF dialysate concentration, we calculated the power relationship between D/S ratios of serum proteins that are only transported across the peritoneum and the molecular weights of those proteins. The measured VEGF D/S ratio was higher than expected (P <.001) in each observation, pointing to local production of VEGF. LVEGF increased with duration of glucose PD, 11.7 ng/L to 23.45 ng/L (P <.03). LVEGF decreased in all 4 patients undergoing glucose-free PD, from 57.35 ng/L to 23.10 ng/L. A correlation (r = 0.83, P <.001) was found be-tween the differences in MTAC creatinine between the first and last SPA during glucose-based PD and the difference in LVEGF between these observations. A similar correlation was present between the difference in glucose absorption and the difference in LVEGF (r = 0.85, P <.001). This supports a pathogenetic role of high glucose dialysate concentrations in the development of changes in the peritoneum that are found in long-term PD. Treatment with non-glucose-based PD solutions may inhibit further development of these alterations.
在之前的一项研究中,血管内皮生长因子(VEGF)被发现在接受含葡萄糖的腹膜透析(PD)患者的腹膜组织中局部产生。局部生成的VEGF (LVEGF)与肌酐的传质面积系数(MTAC)和葡萄糖吸收呈正相关,两者均代表腹膜血管表面积。因此,我们假设VEGF参与了长期PD患者腹膜新生血管生成。本研究的目的是在纵向随访期间调查葡萄糖基PD溶液治疗的PD患者腹膜VEGF水平的时间过程。我们还研究了切换到无葡萄糖PD治疗对VEGF产生的影响。采用含3.86%葡萄糖的透析液进行40例标准腹膜通透性分析(spa)。在23个月的随访期间,对10例PD患者进行了spa,每位患者中位数为3次spa。最后一次SPA PD治疗持续时间为74个月。所有患者最初都用含葡萄糖的透析液治疗。4名患者在114个月的葡萄糖基PD治疗后转为无葡萄糖PD治疗,随访7个月。在这些患者中应用了以碘糊精、甘油和氨基酸为基础的透析溶液的PD方案。在此期间,每位患者进行了4次spa。当扩散是VEGF透析液浓度的唯一解释时,为了预测VEGF透析液与血清的比率(D/S),我们计算了仅通过腹膜运输的血清蛋白的D/S比率与这些蛋白的分子量之间的幂关系。在每次观察中,测量到的VEGF D/S比均高于预期(P < 0.001),表明VEGF在局部产生。LVEGF随葡萄糖PD持续时间增加,从11.7 ng/L增加至23.45 ng/L (P < 0.05)。4例无糖PD患者LVEGF均下降,从57.35 ng/L降至23.10 ng/L。在第一次和最后一次SPA中MTAC肌酐的差异与LVEGF的差异之间存在相关性(r = 0.83, P < 0.001)。葡萄糖吸收差异与LVEGF差异之间存在类似的相关性(r = 0.85, P < 0.001)。这支持了高葡萄糖透析液浓度在腹膜变化发展中的病理作用,这种变化在长期PD中发现。用非葡萄糖基PD溶液治疗可能会抑制这些改变的进一步发展。
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引用次数: 107
cDNA cloning and immunologic characterization of Pen o 18, the vacuolar serine protease major allergen of Penicillium oxalicum. 草青霉液泡丝氨酸蛋白酶主要变应原p18cdna克隆及免疫特性研究。
Pub Date : 2001-02-01 DOI: 10.1067/MLC.2001.112096
H. Shen, C. Wang, W. L. Lin, H. Lai, M. Tam, H. Chou, S. R. Wang, S. H. Han
Penicillium species are prevalent indoor airborne fungi that have been identified as causative agents of human extrinsic bronchial asthma. In the preparation of standardized diagnostic reagents, it is imperative to define the allergens of these ubiquitous fungi. Results from our previous study on P. oxalicum suggest that the 34-kd major immunoglobulin E-reacting component of this prevalent Penicillium species is probably a vacuolar serine protease. The purpose of the present study was to define this major P. oxalicum allergen (Pen o 18) through cDNA cloning and immunologic characterization. The cDNA of Pen o 18 was isolated through a combination of reverse transcriptase-polymerase chain reaction and 5'- and 3'-rapid amplification cDNA ends reactions. The primers used in these reactions were constructed according to the internal amino acid sequences of Pen o 18 and the conserved amino acid sequences of fungal serine proteases. Our results showed that a 1897-bp cDNA with an open reading frame of 503 residues was isolated for the proenzyme of Pen o 18. The encoded protein has a 16-residue signal peptide and a 119-residue prosequence. On maturation, the protein has an N-terminal glutamate that is the 136th residue encoded by the cDNA. Apparently the precursor also undergoes C-terminal processing with the cleavage of about 47 amino acids. The cDNA for Pen c 18 (the vacuolar serine protease allergen from P. citrinum ) was also isolated for comparison. Contrary to a previous report, the C-terminal region of Pen c 18 is similar to that of Pen o 18. Recombinant proteins (rPen o 18 and rPen c 18) with the putative mature N-termini and a his-tag were obtained by expressing the corresponding cDNAs in Escherichia coli. Serum samples from 7 asthmatic patients with immunoglobulin E reactivity to the 34-kd component of P. oxalicum also react to his-tagged recombinant Pen o 18. The presence of immunoglobulin E cross-reactivity between rPen o 18 and rPen c 18 was detected by immunoblot inhibition. Two monoclonal antibodies (PCM39 and FUM20) against fungal serine proteases react with rPen o 18, rPen c 18, and the 35/34-kd components in the corresponding crude fungal extracts. These components also react with immunoglobulin E antibodies in serum samples from asthmatic patients. In conclusion, results obtained confirm that the 34-kd major allergen of P. oxalicum is a vacuolar serine protease. The cDNAs of Pen o 18 and Pen c 18 encode precursor molecules that appear to undergo both N-terminal and C-terminal processing. Constructs beginning with mature N-terminal can be expressed in E. coli to produce recombinant polypeptides that are reactive to monoclonal antibodies or immunoglobulin E antibodies in serum samples from asthmatic patients. Results obtained may provide useful information and materials for preparation of standardized diagnostic reagents in clinical mold allergy.
青霉菌是一种常见的室内空气传播真菌,已被确定为人类外源性支气管哮喘的病原体。在标准化诊断试剂的制备中,必须明确这些普遍存在的真菌的过敏原。我们之前对P. oxalicum的研究结果表明,这种流行的青霉菌种的34-kd主要免疫球蛋白e反应成分可能是空泡丝氨酸蛋白酶。本研究的目的是通过cDNA克隆和免疫学鉴定来确定这一主要的草藻变应原(Pen o 18)。采用逆转录聚合酶链反应和5′、3′快速扩增cDNA末端反应相结合的方法,分离得到了p8018的cDNA。这些反应中使用的引物是根据Pen o 18的内部氨基酸序列和真菌丝氨酸蛋白酶的保守氨基酸序列构建的。结果表明,该基因原酶cDNA全长1897-bp,开放阅读框为503个残基。编码的蛋白具有16个残基的信号肽和119个残基的序列。成熟时,该蛋白具有n端谷氨酸,这是cDNA编码的第136个残基。显然前体也经历c端加工,裂解约47个氨基酸。此外,我们还分离到了penc18的cDNA进行比较。与之前的报道相反,Pen c18的c端区域与Pen o18相似。通过在大肠杆菌中表达相应的cdna,获得了具有假定的成熟n端和his标签的重组蛋白(rPen o - 18和rPen c - 18)。7例哮喘患者血清中免疫球蛋白E对草草草34-kd组分有反应,对his标记的重组p18也有反应。采用免疫印迹法检测rPen o18与rPen c18之间是否存在免疫球蛋白E交叉反应。两种抗真菌丝氨酸蛋白酶的单克隆抗体(PCM39和FUM20)与rPen o 18、rPen c 18和相应粗真菌提取物中的35/34-kd组分发生反应。这些成分还能与哮喘患者血清样本中的免疫球蛋白E抗体发生反应。综上所述,这些结果证实了草藻的34-kd主要变应原是一种空泡丝氨酸蛋白酶。Pen o18和Pen c18的cdna编码的前体分子似乎经历了n端和c端加工。以成熟n端开头的构建体可以在大肠杆菌中表达,产生对哮喘患者血清样品中的单克隆抗体或免疫球蛋白E抗体有反应的重组多肽。所得结果可为临床霉菌过敏的标准化诊断试剂的制备提供有用的信息和资料。
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引用次数: 40
ApaI polymorphisms of the vitamin D receptor predict bone density of the lumbar spine and not racial difference in bone density in young men. 维生素D受体ApaI多态性预测腰椎骨密度,而不是年轻男性骨密度的种族差异。
Pub Date : 2001-02-01 DOI: 10.1067/MLC.2001.112095
N. Bell, N. Morrison, Tuan V. Nguyen, J. Eisman, B. Hollis
A number of previous investigations showed significant associations between polymorphisms of the vitamin D receptor (VDR) gene and bone mineral density (BMD). BMD is influenced by hormones and the rate of skeletal remodeling. A study was performed to investigate the possible relationship between Apa I, Bsm I, Taq I, and Fok I polymorphisms of the VDR gene and serum 1,25-dihydroxyvitamin D (1,25[OH]2D), osteocalcin, and propeptide of type I collagen (PICP)-markers of bone turnover, total body calcium, and BMD of the total body, radius, lumbar spine, trochanter, and femoral neck-in 39 young adult black men of 20 to 40 years of age and 44 age-, height-, and weight-matched white men. The distribution of each of the four alleles of the VDR genotypes was similar in the two racial groups. The Apa I VDR genotype was associated with serum PICP (P =.0494) but not with serum 1,25(OH)2D or serum osteocalcin. A significant association between the Apa I VDR genotype and BMD of the lumbar spine (P =.0291) was also observed. However, the Bsm I, Taq I, and Fok I genotypes were not significantly associated with BMD or serum osteocalcin, PICP, or 1,25(OH)2D. Multivariate stepwise analysis indicated that (1) the Apa I VDR genotype was associated with BMD of the lumbar spine in the two groups together; with total body calcium and BMD of the total body, radius, trochanter, and femoral neck in the black men; and with BMD of the radius in the white men; analysis also indicated that (2) race was significantly associated with total body calcium and BMD of the total body, lumbar spine, and femoral neck. In summary, the Apa I VDR genotype is associated with serum PICP and BMD at a number of sites but does not contribute to or account for racial differences in BMD in young adult men.
先前的一些研究表明,维生素D受体(VDR)基因多态性与骨矿物质密度(BMD)之间存在显著关联。骨密度受激素和骨骼重塑速率的影响。进行的一项研究调查Apa我之间可能的关系,Bsm, Taq我,霍英东我VDR基因多态性和血清1,25-dihydroxyvitamin D(1,25(哦)2 D)、骨钙素,和前肽的I型胶原蛋白(PICP)标记的骨代谢,全身钙,和全身的骨密度,半径,腰椎,转子,和股骨的39个年轻人20到40岁的黑人男性,44岁,身高,和weight-matched白人。VDR基因型的4个等位基因在两个种族群体中的分布相似。Apa I VDR基因型与血清PICP相关(P = 0.0494),但与血清1,25(OH)2D或血清骨钙素无关。Apa I VDR基因型与腰椎骨密度有显著相关性(P = 0.0291)。然而,Bsm I、Taq I和Fok I基因型与BMD或血清骨钙素、PICP或1,25(OH)2D没有显著相关。多因素逐步分析表明:(1)Apa I VDR基因型与两组腰椎骨密度均相关;黑人男性的全身、桡骨、粗隆和股骨颈的总钙和骨密度;与白人的桡骨骨密度有关;分析还表明(2)种族与全身、腰椎和股骨颈的总钙和骨密度显著相关。总之,Apa I VDR基因型在许多位点与血清PICP和骨密度相关,但不能解释年轻成年男性骨密度的种族差异。
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引用次数: 33
An analysis of renal nitric oxide contribution to hyperfiltration in diabetic rats. 肾脏一氧化氮对糖尿病大鼠高滤过的作用分析。
Pub Date : 2001-02-01 DOI: 10.1067/MLC.2001.112691
D. Schwartz, I. Schwartz, R. Blantz
We have investigated whether nitric oxide (NO) generation is increased in diabetes and whether specific NO synthase (NOS) isoforms are up-regulated in 4-week diabetic male Wistar rats. Glomerular filtration rate (GFR), kidney weight, and urinary nitrate (NOx) generation were measured in the following groups (n = 6): normal control animals, diabetic animals, diabetic animals given L -NIL (a selective iNOS inhibitor)(D + L -NIL), diabetic animals given L -NAME (a nonselective NOS inhibitor)(D + L -NAME), and control animals given L -NAME (C + L -NAME). Diabetes increased GFR (0.78 +/- 0.05 mL/min/100 g body wt vs 1.49 +/- 0.07 mL/min/100 g body wt, P <.01). L -NIL did not affect hyperfiltration, while L -NAME decreased GFR to values that were lower than those in normal control animals, a response identical to that in non-diabetic control rats. L -NIL did not affect urinary NOx values, but L -NAME completely abolished the increase in urinary nitrates. Kidney weight was not affected by L -NIL, but L -NAME significantly attenuated kidney growth. Inducible NOS (iNOS) and endothelial NOS (eNOS) mRNA levels measured by reverse transcription-polymerase chain reaction in diabetic rats were not changed as compared with levels in controls. Cyclic guanosine monophosphate responses to carbachol (an index of eNOS activity) in glomeruli from diabetic rats were significantly reduced as compared with those in controls, and guanylate cyclase responses to sodium nitroprusside were significantly decreased. Therefore, renal NO generation, at least via eNOS and iNOS, is not the primary cause of glomerular hyperfiltration in diabetes.
我们研究了在糖尿病4周的雄性Wistar大鼠中,一氧化氮(NO)的生成是否增加,以及特定的NO合成酶(NOS)异构体是否上调。测定各组(n = 6)的肾小球滤过率(GFR)、肾脏重量和尿硝态氮(NOx)生成:正常对照动物、糖尿病动物、给予L -NIL(选择性NOS抑制剂)(D + L -NIL)的糖尿病动物、给予L -NAME(非选择性NOS抑制剂)(D + L -NAME)的糖尿病动物和给予L -NAME (C + L -NAME)的对照动物。糖尿病增加GFR (0.78 +/- 0.05 mL/min/100 g body wt vs 1.49 +/- 0.07 mL/min/100 g body wt, P < 0.01)。L -NIL不影响超滤,而L -NAME使GFR降低到低于正常对照动物的水平,与非糖尿病对照大鼠的反应相同。L -NIL不影响尿NOx值,但L -NAME完全消除了尿硝酸盐的增加。肾脏重量不受L -NIL的影响,但L -NAME显著抑制肾脏生长。通过逆转录聚合酶链反应测定的糖尿病大鼠诱导型NOS (iNOS)和内皮型NOS (eNOS) mRNA水平与对照组相比没有变化。与对照组相比,糖尿病大鼠肾小球中环鸟苷单磷酸反应(eNOS活性指标)显著降低,鸟苷环化酶对硝普钠的反应显著降低。因此,肾脏生成NO,至少通过eNOS和iNOS,并不是糖尿病肾小球高滤过的主要原因。
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引用次数: 28
Manipulating the vascular biology of coronary atherosclerosis in diabetes: new opportunities. 控制糖尿病冠状动脉粥样硬化的血管生物学:新的机遇。
Pub Date : 2001-02-01 DOI: 10.1067/MLC.2001.110970
J. Orford, S. Kinlay, J. Fernandes, D. Behrendt, P. Ganz, A. Selwyn
ore than 7 million people in the United States of America have diabetes mellitus, and type 2 diabetes and the insulin resistance syndrome are increasingly prevalent. This is thought to be the result of the aging of the population, the increasing prevalence of obesity, the growing contribution of highrisk minority groups, and a lower glycemic threshold for the diagnosis of diabetes. The insulin resistance syndrome (syndrome X) describes the clustering of a number of metabolic abnormalities that are risk factors for both diabetes mellitus and atherosclerotic cardiovascular disease.1 These risk factors include hyperinsulinemia, impaired glucose tolerance, hypertension, and a characteristic dyslipidemia (Table I).2 An alternative name, the cardiovascular dysmetabolic syndrome, has been proposed in an effort to emphasize the cardiovascular consequences of this syndrome (Table II).3 Accelerated atherosclerosis is a common and very important feature of both diabetes and insulin resistance, and atherosclerotic cardiovascular disease is responsible for at least three quarters of all diabetesrelated deaths.4,5 Microvascular complications of diabetes are improved by maintenance of tight long-term glycemic control, whereas it has proved difficult to show that atherosclerosis of the large conduit arteries and its complications are prevented by glycemic control.6,7 Aggressive treatment of cardiovascular risk factors associated with the insulin resistance syndrome and diabetes mellitus, including hypertension and dyslipidemia, is effective in reducing the relative risk of cardiovascular events in diabetic patients.8,9 This review focuses on the cell/vessel wall dysfunctions in these syndromes that cause atherosclerosis and the new therapeutic opportunities that follow.
美国有700多万人患有糖尿病,2型糖尿病和胰岛素抵抗综合征日益普遍。这被认为是人口老龄化、肥胖患病率上升、高风险少数群体的贡献增加以及糖尿病诊断的血糖阈值较低的结果。胰岛素抵抗综合征(X综合征)描述了一系列代谢异常的聚集,这些异常是糖尿病和动脉粥样硬化性心血管疾病的危险因素这些危险因素包括高胰岛素血症、糖耐量受损、高血压和特征性血脂异常(表1)为了强调该综合征对心血管的影响,已经提出了另一个名称,即心血管代谢不良综合征(表2)动脉粥样硬化的加速是糖尿病和胰岛素抵抗的一个常见且非常重要的特征,动脉粥样硬化性心血管疾病导致至少四分之三的糖尿病相关死亡。4,5糖尿病的微血管并发症可以通过长期严格的血糖控制得到改善,而大导管动脉粥样硬化及其并发症很难通过血糖控制得到预防。6,7积极治疗与胰岛素抵抗综合征和糖尿病相关的心血管危险因素,包括高血压和血脂异常,可有效降低糖尿病患者心血管事件的相对风险。8,9这篇综述的重点是在这些综合征中引起动脉粥样硬化的细胞/血管壁功能障碍以及随之而来的新的治疗机会。
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引用次数: 4
Protective effect of anisodamine against Shiga toxin-1: inhibition of cytokine production and increase in the survival of mice. 山莨菪碱对志贺毒素1的保护作用:抑制细胞因子的产生,提高小鼠的存活率。
Pub Date : 2001-02-01 DOI: 10.1067/MLC.2001.112507
H. Zhang, Z. Ou, F. Gondaira, M. Ohmura, S. Kojio, T. Yamamoto
The purpose of this study was to investigate whether anisodamine could inhibit Shiga toxin-1 (Stx1)-induced cytokine production and increase the survival of Stx1-treated mice. Human monocytic cells were stimulated by Stx1 (1 to 100 ng/mL) with or without anisodamine addition (1 to 400 microg/mL). For in vivo evaluations, C57BL/6 mice were given a single intraperitoneal injection of anisodamine (1 mg) or saline solution after intraperitoneal injection of Stx1 (2.75 microg/kg). The results showed that anisodamine significantly suppressed Stx1-induced tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-8 production. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that anisodamine suppressed Stx1-mediated TNF-alpha mRNA expression. Further study showed that this TNF-alpha inhibitory effect was via a prostaglandin E2-dependent mechanism. Anisodamine treatment prolonged the survival time of mice and decreased the lethality of Stx1 (94.5% to 44%). Because cytokines, in particular TNF-alpha, contribute to the pathologic process in Stx-producing Escherichia coli (STEC) infection, this study suggested that anisodamine could be a potential drug for treatment of STEC infection.
本研究的目的是探讨山莨菪碱是否能抑制志贺毒素1 (Stx1)诱导的细胞因子的产生,并提高Stx1处理小鼠的存活率。Stx1 (1 ~ 100 ng/mL)加山莨菪碱(1 ~ 400 μ g/mL)刺激人单核细胞。在体内试验中,C57BL/6小鼠腹腔注射Stx1(2.75微克/千克)后,单次腹腔注射山莨菪碱(1毫克)或生理盐水。结果表明,山莨菪碱显著抑制stx1诱导的肿瘤坏死因子- α (tnf - α)、白细胞介素-1 β (il -1 β)和IL-8的产生。逆转录聚合酶链反应(RT-PCR)显示山莨菪碱抑制stx1介导的tnf - α mRNA表达。进一步的研究表明,这种抑制tnf - α的作用是通过前列腺素e2依赖的机制。山莨菪碱处理可延长小鼠存活时间,降低Stx1致死率(94.5% ~ 44%)。由于细胞因子,特别是tnf - α,参与了产stx大肠杆菌(STEC)感染的病理过程,本研究提示山莨菪碱可能是治疗STEC感染的潜在药物。
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引用次数: 17
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The Journal of laboratory and clinical medicine
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