Coronary arterial remodeling: From bench to bedside

Coronary arterial remodeling describes changes of vessel size at the site of atherosclerotic lesions. Positive remodeling (expansion) of early lesions maintains lumen size despite plaque accumulation. In contrast, negative remodeling (shrinkage) contributes to luminal stenosis independent of plaque accumulation. Because of these adaptive changes, plaque progression/regression is not closely reflected in luminal size. Histologic studies have demonstrated that the pathophysiologic role of arterial remodeling is more complex than a mere compensatory process. Surprisingly, there is a consistent association between positive arterial remodeling, local inflammatory response, and plaque vulnerability. In vivo tomographic imaging techniques, in particular intravascular ultrasound, and potentially computed tomography and magnetic resonance imaging, allow the observation of remodeling in clinical settings. The integration of basic knowledge about arterial remodeling with clinical observations from in vivo imaging could lead to a better understanding of plaque progression, regression, and vulnerability and may eventually have implications for disease prevention.     

甘草次酸类化合物的制备和抗肿瘤活性研究

目的制备18α-和18β-甘草次酸类复合物,并对体外抗癌活性进行研究。方法以18β-甘草次酸(Ⅰ)为起点,进行构型转化得到其光学异构体18α-甘草次酸(Ⅱ),再经C30-位羧基的甲酯化分别得到18β-甘草次酸甲酯(Ⅲ)和18-α-甘草次酸甲酯(Ⅳ),并与环磷酰胺的抗癌活性体内代谢产物——二氯磷酰氮芥偶联而得2个抗癌复合物18β-甘甲磷氮芥(Ⅴ)和18α-甘甲磷氮芥(Ⅵ);用四大光谱法(NMR、MS、IR、UV)对各化合物的化学结构进行鉴定分析;利用人类肝癌细胞株BEL-7402为体外实验模型,用MTT法观察各化合物对人肝癌细胞增殖的抑制活性;抗肿瘤药物顺铂作为阳性对照物。结果对化合物的合成工艺进行优化;18α-甘草次酸的构象转化得率为45%;目标化合物18β-甘甲磷氮芥(Ⅴ)和18α-甘甲磷氮芥(Ⅵ)的产率分别为35%和25%。所制备的甘草次酸衍生物中,化合物Ⅱ和Ⅵ对BEL-7402肿瘤细胞的增殖显示明显强的抑制活性,浓度在5～500μg/mL范围内,对肿瘤细胞增殖的抑制率分别为2.6%～86%及1.3%～50.1%;在相同条件下,对照物顺铂的抑制率为20.0%～73.41%。结论目标化合物的制备中磷酰酯化反应的条件控制(无水、物料比1∶1.25,温度65℃和反应时间3～4h)是合成关键;化合物Ⅱ和Ⅵ在中高浓度时,与顺铂具有较类似的抑制肝癌细胞增殖活性。甘草次酸类化合物的构型转化及与抗癌基团偶联可能提高其抗癌潜力。     

Hemodynamic Changes in a Model of Chronic Heart Failure Induced by Multiple Sequential Coronary Microembolization in Sheep

Although a large variety of animal models for acute ischemia and acute heart failure exist, valuable models for studies on the effect of ventricular assist devices in chronic heart failure are scarce. We established a stable and reproducible animal model of chronic heart failure in sheep and aimed to investigate the hemodynamic changes of this animal model of chronic heart failure in sheep. In five sheep (n = 5, 77 ± 2 kg), chronic heart failure was induced under flouroscopic guidance by multiple sequential microembolization through bolus injection of polysterol microspheres (90 µm, n = 25.000) into the left main coronary artery. Coronary microembolization (CME) was repeated up to three times in 2 to 3‐week intervals until animals started to develop stable signs of heart failure. During each operation, hemodynamic monitoring was performed through implantation of central venous catheter (central venous pressure [CVP]), arterial pressure line (mean arterial pressure [MAP]), implantation of a right heart catheter {Swan‐Ganz catheter (mean pulmonary arterial pressure [PAPmean])}, pulmonary capillary wedge pressure (PCWP), and cardiac output [CO]) as well as pre‐ and postoperative clinical investigations. All animals were followed for 3 months after first microembolization and then sacrificed for histological examination. All animals developed clinical signs of heart failure as indicated by increased heart rate (HR) at rest (68 ± 4 bpm [base] to 93 ± 5 bpm [3 mo][P < 0.05]), increased respiratory rate (RR) at rest (28 ± 5 [base] to 38 ± 7 [3 mo][P < 0.05]), and increased body weight 77 ± 2 kg to 81 ± 2 kg (P < 0.05) due to pleural effusion, peripheral edema, and ascites. Hemodynamic signs of heart failure were revealed as indicated by increase of HR, RR, CVP, PAP, and PCWP as well as a decrease of CO, stroke volume, and MAP 3 months after the first CME. Multiple sequential intracoronary microembolization can effectively induce myocardial dysfunction with clinical and hemodynamic signs of chronic ischemic cardiomyopathy. The present model may be suitable in experimental work on heart failure and left ventricular assist devices, for example, for studying the impact of mechanical unloading, mechanisms of recovery, and reverse remodeling.     

Hyperthyroidism may affect serum N-terminal pro-B-type natriuretic peptide levels independently of cardiac dysfunction

BACKGROUND AND AIM: It is known that NT-proBNP levels increase in cardiac failure. However, NT-proBNP levels in different thyroid states are still unclear. We aimed to evaluate serum NT-proBNP levels in both hyperthyroid and hypothyroid patients without cardiac insufficiency. SUBJECTS AND METHODS: Thirty-six patients with hyperthyroidism (42.9 +/- 16.7 years), 25 patients with hypothyroidism (35.4 +/- 13.9 years) and 34 age-matched euthyroid subjects (41.4 +/- 13.8 years) were included in the study. After anthropometric evaluations, body fat analyses were determined by bioelectrical impedance. Electrocardiography and echocardiography were used in cardiac evaluations. Serum NT-proBNP was measured by immunoassay. RESULTS: Mean serum NT-proBNP levels in hyperthyroid patients were higher than in both control subjects (13.65 +/- 13.02 vs. 6.50 +/- 4.83 pmol/l, P = 0.002) and hypothyroid patients (13.65 +/- 13.02 vs. 5.98 +/- 5.08 pmol/l, P = 0.003). However, mean serum NT-proBNP levels in hypothyroid patients were not different from those in control subjects. There was a positive correlation between serum NT-proBNP and thyroid hormones (NT-proBNP and FT3: r = 0.324, P = 0.001; NT-proBNP and FT4: r = 0.269, P = 0.009, respectively). Serum NT-proBNP levels were positively correlated with left ventricle end-diastolic diameters (r = 0.232, P = 0.04), interventricular septum thickness (r = 0.315, P = 0.006), and negatively correlated with left ventricular ejection fraction (r = -0.238, P = 0.04). CONCLUSIONS: Serum NT-proBNP levels may increase in hyperthyroidism independently of cardiac insufficiency. Therefore, hyperthyroidism may lead to cardiac ultrastructural changes undetermined by conventional echocardiography and these changes may be responsible for elevation of NT-proBNP levels. In contrast to decreased thyroid hormones, excess thyroid hormones may have a more pronounced effect on serum NT-proBNP levels.     

Altered JS-2 expression in colorectal cancers and its clinical pathological relevance

JS-2 is a novel gene located at 5p15.2 and originally detected in primary oesophageal cancer. There is no study on the role of JS-2 in colorectal cancer. The aim of this study is to determine the gene copy number and expression of JS-2 in a large cohort of patients with colorectal tumours and correlate these to the clinicopathological features of the cancer patients. We evaluated the DNA copy number and mRNA expression of JS-2 in 176 colorectal tissues (116 adenocarcinomas, 30 adenomas and 30 non-neoplastic tissues) using real-time polymerase chain reaction. JS-2 expression was also evaluated in two colorectal cancer cell lines and a benign colorectal cell line. JS-2 amplification was noted in 35% of the colorectal adenocarcinomas. Significant differences in relative expression levels for JS-2 mRNA between different colorectal tissues were noted (p = 0.05). Distal colorectal adenocarcinoma had significantly higher copy number than proximal adenocarcinoma (p = 0.005). The relative expression level of JS-2 was different between colonic and rectal adenocarcinoma (p = 0.007). Mucinous adenocarcinoma showed higher JS-2 expression than non-mucinous adenocarcinoma (p = 0.02). Early T-stage cancers appear to have higher JS-2 copy number and lower expression of JS-2 mRNA than later stage cancers (p = 0.001 and 0.03 respectively). Colorectal cancer cell lines showed lower expression of JS-2 than the benign colorectal cell line. JS-2 copy number change and expression were shown for the first time to be altered in the carcinogenesis of colorectal cancer. In addition, genetic alteration of JS-2 was found to be related to location, pathological subtypes and staging of colorectal cancer.     

Radiological and dermatological findings in two patients suffering from early yaws in Indonesia.

Two children suffering from early yaws in Indonesia are presented. Apart from skin lesions and a positive treponemal serology in both patients, involvement of tubular bones, particularly of the hands, was revealed by radiological examination. In one patient involvement of a distal phalanx was remarkable. Early diagnosis and treatment of yaws is important since a delay in treatment may result in severe and irreversible bone deformities of the late stage of the disease. This report illustrates that radiological changes, although rare, can still be detected in the early stage of yaws in areas where yaws is resurgent nowadays.     

Three column stabilization through posterior approach alone: transpedicular placement of distractable cage with transpedicular screw fixation

The combination of anterior and posterior instrumentation provides the most stable repair for burst fractures of the thoracolumbar spine. However, the use of both approaches on a trauma patient may increase morbidity. Stabilization of three columns through only one approach can provide an effective outcome. We treated eight patients with burst fracture involving the thoracic or lumbar vertebrae by the application of anterior and posterior stabilization instruments through only the posterior approach. The desired stabilization was obtained in all patients. The advantages are the absence of the risks of the anterior approach, facilitation of the placement of anterior and posterior stabilization devices through only one approach, preserving the unity of the anterior longitudinal ligament, the effect of the anterior corpus in preventing displacement of the cage, application of compression on the pedicle screw system to both decrease the kyphosis angulation due to collapse of vertebra and to help the stabilization of the cage, repair of the dural tears at the posterior side, prevention of cage displacement by distraction and thus leaning on the endplates, and ease of performance by a neurosurgeon alone.     

Zinc supplementation ameliorates electromagnetic field-induced lipid peroxidation in the rat brain

Extremely low-frequency (0-300 Hz) electromagnetic fields (EMFs) generated by power lines, wiring and home appliances are ubiquitous in our environment. All populations are now exposed to EMF, and exposure to EMF may pose health risks. Some of the adverse health effects of EMF exposure are lipid peroxidation and cell damage in various tissues. This study has investigated the effects of EMF exposure and zinc administration on lipid peroxidation in the rat brain. Twenty-four male Sprague-Dawley rats were randomly allocated to three groups; they were maintained untreated for 6 months (control, n = 8), exposed to low-frequency (50 Hz) EMF for 5 minutes every other day for 6 months (n = 8), or exposed to EMF and received zinc sulfate daily (3 mg/kg/day) intraperitoneally (n = 8). We measured plasma levels of zinc and thiobarbituric acid reactive substances (TBARS), and levels of reduced glutathione (GSH) in erythrocytes. TBARS and GSH levels were also determined in the brain tissues. TBARS levels in the plasma and brain tissues were higher in EMF-exposed rats with or without zinc supplementation, than those in controls (p < 0.001). In addition, TBARS levels were significantly lower in the zinc-supplemented rats than those in the EMF-exposed rats (p < 0.001). GSH levels were significantly decreased in the brain and erythrocytes of the EMF-exposed rats (p < 0.01), and were highest in the zinc-supplemented rats (p < 0.001). Plasma zinc was significantly lower in the EMF-exposed rats than those in controls (p < 0.001), while it was highest in the zinc-supplemented rats (p < 0.001). The present study suggests that long-term exposure to low-frequency EMF increases lipid peroxidation in the brain, which may be ameliorated by zinc supplementation.     

腺点金丝桃挥发油化学成分分析

目的:研究腺点金丝桃挥发油成分及相对含量。方法:本文用水蒸气蒸馏,乙酸乙酯萃取法提取腺点金丝桃挥发油。采用GC-MS分析对其挥发油进行分离鉴定。结果:确定了41种成分,占挥发油总量的92.61,其中39种为首次报道。结论:萃取物中主要含:β-萜品烯反3.7-二甲基1.3.6-辛三烯、-顺3.7-二甲基1.3.6-辛三烯、δ-杜松萜烯、γ-杜松贴烯、长叶薄荷酮。