贝母生物碱的体外气管松弛作用研究(英文)

目的:贝母是一种常用的传统止咳中药, 贝母生物碱被认为是其镇咳的主要活性成分,但其作用机理和各种生物碱的作用强度仍然不是很明确。方法:选用离体大鼠气管和支气管作为体外模型并用卡巴胆碱诱导其收缩, 研究和比较了5种主要贝母生物碱[imperialine(IMP),verticine(VER),verticinone(VERN), ebeiedine(EBE)和puqietinone(PUQ)] 的舒张作用。结果:5种贝母生物碱均有气管和支气管舒张作用并呈量效关系, 其活性强度为IMP>VER≌VERN>EBE>PUQ。在所测试的生物碱中,IMP(D和E环顺式异甾体贝母生物碱)的舒张作用最强; 而 PUQ(甾体贝母生物碱)的舒张作用最弱。此外,3种贝母生物碱,IMP,VER和VERN(≥1μmol·L-1) 能引致卡巴胆碱浓度反应曲线平行右移, 证明他们的作用机理是对M受体具竞争性拮抗作用。同时抑制钙离子的流入亦可能是贝母生物碱舒张气管和支气管的另一作用机理。结论:异甾体贝母生物碱可能是贝母的主要活性成分,其作用机理为竞争性拮抗胆碱能受体并抑制钙离子的流入。     

Distribution and Magnitude of Shear Stress after Coronary Bifurcation Lesions Stenting with the Classical Crush Technique: A New Predictor for In‐Stent Restenosis

Background: Wall shear stress (SS) plays an important role in the initiation and proliferation of coronary atherosclerosis, especially for bifurcations. Stenting in the coronary artery will cause many different changes in velocity, flow, cross‐sectional area, and especially the wall SS. However, it is still unknown how much wall SS distribution varies with stenting in coronary bifurcation. Objective: The purpose of this study was to investigate the magnitude and distribution of wall SS after the classical crush stenting for bifurcation lesions. Methods: Eleven patients with true coronary bifurcation stenting by the classical crush technique were included. We studied the difference of wall SS between restenosis and nonrestenosis groups in these patients. The differences in SS between preprocedure and postprocedure, as well as between immediately postprocedure and after an 8‐month follow‐up, were also analyzed. Diameter stenosis or minimal lumen diameter were measured by quantitative coronary analysis. The commercial CD STAR‐CCM+ was used to calculate the SS. Results: At baseline, the SS in all the segments of all patients was high. The baseline SS of the restenosis group was 50% lower than the nonrestenosis group. Immediately after percutaneous coronary intervention (PCI), the SS in both areas decreased; however, the SS of the nonrestenosis group decreased to its lowest level possible while the SS of the restenosis group decreased moderately. Eight months later, the SS of all the segments of the nonrestenosis group remained persistently low at the same level of right after PCI. In contrary, the SS in the restenosis group returned to near its baseline level. Conclusion: From our study, after a 2‐stent crush technique using drug‐eluting stents (DES), the degree of SS reduction appears to predict in‐stent restenosis (ISR). A SS decrease to its lowest level and remaining homogenously low is a prime condition to prevent ISR. A baseline low SS, which decreases minimally after PCI and recovers to around its baseline level, appears to be the setting for restenosis. These conditions can be evaluated as predictors of lesions that may need surveillance angiography and proper IVUS evaluation to prevent future in‐stent restenosis. (J Interven Cardiol 2010;23:330–340)     

提高中草药随机对照试验的质量Ⅰ:临床试验设计和方法学

目的:通过对中草药临床随机对照试验的设计及方法学进行质量评价,探讨如何提高中草药临床试验的质量。方法:文献检索2005年7月前发表于Cochrane图书馆的中草药系统评价共11篇,包含167个中草药临床随机对照试验。质量评价方法采用修订版CONSORT声明9项指标以及中草药剂型及质量控制标准指标。结果:所有167个临床试验都含有试验目的、方法、第1结局指标、统计学方法及中药剂型;其中163(97.6%)个临床试验说明了研究对象的纳入标准,只有26(15.6%)个临床试验说明了研究对象的排除标准;只有14(8.4%)个临床试验详细说明了随机序列的产生方法;4(2.4%)个临床试验提及了随机分配隐藏;绝大部分的临床试验(86.8%)属于开放性的,只有13.2%的临床试验采用了盲法设计;只有1个临床试验在试验前进行了样本含量的计算;在中草药剂型方面,45.5%的临床试验使用的是汤剂或中药茶包,只有1个临床试验提及了制剂的质量控制。在167个临床试验中,所有质量评价指标的涉及率只有36.0%。结论:现阶段中草药临床随机对照试验的质量还很低。建议:(1)试验设计者及实施者必须接受正规的临床试验基础知识的培训;(2)推荐采用临床试验设计流程图,逐一解决临床试验过程中的关键问题;(3)在方案正式实施前进行预试验,并根据预试验的结果对临床试验设计方案进行调整;(4)对临床试验设计的最终方案进行注册登记,并预先发表(最好是网上发表)临床试验设计方案;(5)广泛开展国际合作,特别是与对中医药研究感兴趣的国际知名学术研究机构进行合作,以提高中草药临床研究的质量。     

A cross-sectional study of growth, puberty and endocrine function in patients with thalassaemia major in Hong Kong

Methodology: A cross-sectional study of growth, puberty and endocrine function was performed on 35 girls and 33 boys with thalassaemia major.
Results Despite regular transfusion and chelation therapy, 75% of the girls and 62% of the boys over the age of 12 years were below the third percentile for height. Hypogonadotropic hypogonadism was found in a similar percentage of patients. Moderate to marked zinc deficiency secondary to chelation therapy was considered unlikely because normal serum zinc levels were found in all but three of our patients, but we could not exclude the possibility of a marginal status of zinc nutrition causing growth failure. Growth hormone deficiency and diabetes mellitus were sometimes encountered but hypothyroidism, hypoparathyroidism and adrenal insufficiency were rare among our patients. Most of the patients with growth failure had normal growth hormone (GH) response to insulin induced hypoglycaemia. The serum insulin-like growth factor-1 (IGF-1) levels were low in our patients and no significant difference in the serum IGF-1 levels was found between prepubertal children with or without growth failure (0.4±0.1 mU/mL vs 0.37±0.11 mU/mL, P = 0.39). Similarly, no difference in the serum IGF-1 levels was found between pubertal children with or without growth failure (0.48 ± 0.2 U/mL vs 0.56 ±0.14 U/mL, P= 0.26).
Conclusions Delayed sexual maturation and a possible defect in growth unrelated to the GH-IGF-1 axis may be responsible for the growth failure in adolescent children with thalassaemia major.     

Extension Distance Mismatch—An Unrecognized Factor for Suboptimal Side Branch Ostial Coverage in Bifurcation Lesion Stenting

Background: The unsatisfactory side branch (SB) ostial strut coverage remains a problem in coronary bifurcation stenting. Both the surplus and lack of struts at SB ostium may be the causative mechanism. We propose that the inability of available stents to cover the “extension distance” of the bifurcation region is the cause of in‐stent restenosis. Methods: The extension distance (ED) is defined as the maximal distance at the carina tip, which must be covered by the stent struts to ensure optimal coverage of the main branch (MB) and SB openings. A mathematical model was created, representing the key factors that govern geometrical reconfigurations after stent implantation in bifurcations. There are two options—with and without bifurcation region deformation. The theoretical assumptions were tested on a bifurcation model (soft polyvinylchloride polymer tubes) permitting free wall deformations and the following parameters: Parent Vessel, MB, SB diameters of 3.5, 3.0, and 2.5 mm, respectively, with an angle of 45° between the MB and SB. After stenting, final KBI with 3.5 mm and 3.0 mm balloons was performed up to 20 atm. Results: After the carina displacement, the ED, which has to be covered, is considerably smaller if the suboptimal result (DS >50%) at the SB ostium is acceptable. The maximal EDs from the bench test measurements are: Vision, Abbott Vascular – 5.62 mm ± 0.04; Liberte, Boston Scientific Corp. – 5.2 mm ± 0.03; Chopin2, Balton – 4.58 mm ± 0.05; Volo, Invatec – 4.41 mm ± 0.04; Driver, Medtronics – 4.39 mm ± 0.04; BxSonic, Cordis, J&J – 4.48 mm ± 0.05. The theoretical maximal ED of the model is 6.91 mm—28–62% larger than actually observed with different stents. Conclusions: The achievement of perfect ostial coverage of the SB is unsatisfactory with most of the currently available stents, especially when poststenting excessive dilation of the ostium of the SB is performed. (J Interven Cardiol 2010;23:305–318)     

Twenty-Four-Month Update on Double-Kissing Crush Stenting of Bifurcation Lesions

A group of 312 patients who underwent percutaneous coronary intervention for bifurcation lesions at 12 centers in China, Singapore, Thailand, Israel, India, and Japan were enrolled in a prospective, randomized DKCRUSH-1 trial. The goal of the study was to compare the double kissing (DK) crush technique with the classical crush stenting technique. This study was carried out to determine the differences in the rates of final kissing balloon inflations (FKBI) and the long-term clinical outcomes. The 8-month results of the DKCRUSH-1 study have been previously reported. Here, we present several subgroups analysis and a 24-month clinical update. The results confirmed a sustained, lower MACE rate at 24 months with the double kissing (DK) crush stenting technique compared with that for the classical crush stenting technique (18.1% vs. 29.9%, p = 0.044).     

粉防己碱特异抑制大鼠血小板聚集和ATP释放(英文)

AIM: To examine the effects of tetrandrine (Tet) on the aggregation and ATP-release of rat washed platelets induced by several platelet activators. METHODS: Gel-filtration (Sepharose 2B) was used to isolate washed platelets from adult rats and the platelet aggragation and ATP-release were measured simultaneously. RESULTS: In the presence of Ca2 1 mmol · L-1, Tet 300 μmol·L -1 inhibited the aggregation induced by ADP ( 25 μmol · L -1), collagen (2.5 g·L-1), and thrombin (103 unit·L-1) by 62 %, 60 %, and 34 %, respectively. It also inhibited arachidonic acid (1 mmol · L-1)-induced aggregation. Elevating intracellular Ca2 concentration with the Ca2 ionophore, calcimycin (30 μmol · L-1), or by blocking the intracellular calcium pump with cyclopiazonic acid (5 μmol · L-1) initiated platelet aggregation, which was also inhibited by Tet. In Ca2 -free medium, Tet still elicited an inhibitory effect on aggregation induced by ristocetin (2.5 g·L-1). Lower concentrations of Tet (30 nmol·L-1 to     

Down-regulation of {beta}-adrenergic receptors on mononuclear leukocytes induced by dobutamine treatment in patients with congestive heart failure

(±)-Dobutamine is a positive inotropic drug usually usedto improve ventricular function in patients with congestiveheart failure (CHF). However, it has been found that haemodynamicresponses to dobutamine become blunted during continuous treatment.In this study we determined the time-dependent changes of ß-adrenergicreceptors in CHF patients treated with dobutamine. Seven CHFpatients received a continuous intravenous infusion of dobutamine(5 µg.kg^–1. min^–1) for 96 h. Blood sampleswere obtained before and every 24 h after starting the therapy.The density of ß-adrenergic receptors on mononuclearleukocytes and the plasma concentrations of norepinephrine andepinephrine were determined. During dobutamine treatment thereceptor density (fmol.mg^–1, mean±SEM) graduallydecreased from 42.8±4.4 (baseline) to 31.4±3.3(P<0.05), 25.2±4.0 (P<0.01), 18.8±5.5 (P<0.01)and 13.4±3.4 (P<0.01) at 24, 48, 72 and 96 h, respectively.However, the plasma concentrations of norepinephrine and epinephrinewere not significantly changed during the 96 h period of treatment.Thus, the ß-adrenergic receptors down-regulated asearly as 24 h after the dobutamine treatment was begun in CHFpatients. This receptor down-regulation was not associated withchanges of plasma catechol-amine concentrations, but was relatedrather to the development of drug tolerance to dobutamine.     

Urinary mitochondrial DNA level as a biomarker of tissue injury in non-diabetic chronic kidney diseases

Background

Urinary mitochondrial DNA (mtDNA) fragment level has been proposed as a biomarker of chronic kidney disease (CKD). In this study, we determine the relation between urinary mtDNA level and rate of renal function deterioration in non-diabetic CKD.

Methods

We recruited 102 non-diabetic CKD patients (43 with kidney biopsy that showed non-specific nephrosclerosis). Urinary mtDNA level was measured and compared to baseline clinical and pathological parameters. The patients were followed 48.3?±?31.8?months for renal events (need of dialysis or over 30% reduction in estimated glomerular filtration rate [eGFR]).

Results

The median urinary mtDNA level was 1519.42 (inter-quartile range 511.81–3073.03) million copy/mmol creatinine. There were significant correlations between urinary mtDNA level and baseline eGFR (r?=?0.429, p?<?0.001), proteinuria (r?=?0.368, p?<?0.001), severity of glomerulosclerosis (r?=???0.537, p?<?0.001), and tubulointerstitial fibrosis (r?=???0.374, p?=?0.014). The overall rate of eGFR decline was ??2.18?±?5.94?ml/min/1.73m² per year. There was no significant correlation between the rate of eGFR decline and urinary mtDNA level. By univariate analysis, urinary mtDNA level predicts dialysis-free survival, but the result became insignificant after adjusting for clinical and histological confounding factors.

Conclusion

Urinary mtDNA levels have no significant association with the rate of renal function decline in non-diabetic CKD, although the levels correlate with baseline renal function, proteinuria, and the severity of histological damage. Urinary mtDNA level may be a surrogate marker of permanent renal damage in non-diabetic CKD.