Synthesis, Characterization and DNA Binding Investigations of a New Binuclear Ag(I) Complex and Evaluation of Its Anticancer Property.

AIM: A new Ag(I) complex (A3) was synthesized and evaluated for its anticancer activity against human cancer cell lines. MATERIALS AND METHODS: The complex A3 was characterized by 1H, 13C, and 31P nuclear magnetic resonance (NMR), infrared (IR) spectra, elemental analysis, and X-ray crystallography. The interaction of the complex with CT-DNA was studied by electronic absorption spectra, fluorescence spectroscopy, and cyclic voltammetry; cell viability (%) was assessed by absorbance measurement of the samples. RESULTS: The interaction mode of the complex A3 with DNA is electrostatic, and this complex shows good potential in anticancer properties against HCT 116 (human colorectal cancer cells) and MDA-MB-231 (MD Anderson-metastatic breast) cell lines with 0.5 micromolar concentrations. CONCLUSION: The Ag(I) complex could interact with DNA noncovalently and has anticancer properties.

The effects of cigarette smoking and smoking cessation on high-density lipoprotein functions: implications for coronary artery disease.

BACKGROUND: Smoking cessation was associated with improved prognosis of coronary artery disease. This study was designed to investigate the effect of smoking cessation on high-density lipoprotein functionality in coronary artery disease patients. METHODS: In this prospective, randomized and parallel controlled study, coronary artery disease smokers ( n = 28) and healthy smokers ( n = 30) were divided into smoking cessation group and continuous smoking group, respectively. Blood samples were collected before and after three-month smoking cessation. Plasma high-density lipoprotein was isolated by density gradient centrifugation. The ability of high-density lipoprotein against copper-induced oxidation of lipoprotein was determined to evaluate the antioxidative property of high-density lipoprotein, and the macrophage migration inhibited by high-density lipoprotein was tested to identify the antichemotactic property of high-density lipoprotein. High-density lipoprotein-induced macrophage cholesterol efflux was measured by fluorescence spectrometry using NBD cholesterol analogue. Healthy non-smoking volunteers were enrolled as the baseline control. RESULTS: The baseline antioxidative, antichemotactic ability of high-density lipoprotein and high-density lipoprotein-induced cellular cholesterol efflux in coronary artery disease smokers and healthy smokers were significantly attenuated when compared with those in healthy non-smokers. After three-month smoking cessation, both the antioxidative ability and antichemotactic ability of high-density lipoprotein were improved significantly in coronary artery disease smokers. However, high-density lipoprotein-induced cellular cholesterol efflux was not increased by smoking cessation. In in vitro experiments, carbon monoxide reduced the antioxidative ability and nicotine enhanced the antichemotactic ability of high-density lipoprotein. CONCLUSIONS: Smoking cessation is an effective measure to improve high-density lipoprotein functions in coronary artery disease smokers. Our study re-emphasizes the importance of smoking cessation in the secondary prevention of coronary artery disease.

The Acute Effects of Cigarette Smoking on the Functional State of High Density Lipoprotein.

BACKGROUND: Cigarette smoking disturbs plasma lipid level and lipoprotein metabolism; however, the effects of smoking on the functional state of high density lipoprotein (HDL) are still not clear. This study aimed to determine the antioxidant and antichemotactic properties of HDL and HDL-mediated cholesterol efflux in healthy subjects after cigarette smoking. MATERIALS AND METHODS: Healthy male subjects, including nonsmokers (n = 16) and chronic smokers (n = 8), were enrolled. After smoking 8 cigarettes within 2 hours, plasma HDL was isolated and tested. Copper-induced low density lipoprotein (LDL) oxidation was used to determine the antioxidant ability of HDL. The concentration of serum amyloid A was measured by Enzyme Linked Immunosorbent Assay. Chemotaxis was detected by transwell assay. HDL-mediated cholesterol efflux was measured using fluorescent cholesterol analog. RESULTS: LDL baseline oxidation state was higher in chronic smokers than that in nonsmokers. Meanwhile, HDL-induced cholesterol efflux in macrophages in chronic smokers was significantly enhanced compared with that in nonsmokers. After acute smoking, both the antioxidant and antichemotactic ability of HDL declined in nonsmokers. However, in healthy chronic smokers, the effect of HDL on the susceptibility of LDL to oxidation was compensatorily enhanced. Nevertheless, their bodies were still in a higher oxidation state. Also, acute smoking did not affect HDL-mediated cholesterol efflux significantly in both nonsmokers and chronic smokers. CONCLUSIONS: Our data suggest that acute smoking attenuates the antioxidant and antichemotactic abilities of HDL in nonsmokers. Chronic smokers are in a higher oxidative state, although the antioxidant function of their HDL is compensatorily enhanced.

Cerebral embolism secondary to cardiac amyloidosis: A case report and literature review.

Cardiac amyloidosis (CA) describes a group of heterogeneous diseases that are characterized by the extracellular fibril deposition of amyloid protein in the myocardium. The abnormal protein is usually derived from light-chain amyloidosis, mutant transthyretin amyloidosis and wild-type transthyretin. Patients with ischemic strokes and amyloidosis have been sporadically reported, however, they are not well summarized. In the present study, a case of cerebral ischemic stroke, secondary to CA was described. This patient presented with dyspnea on exertion, without any evidence of atrial fibrillation. A biopsy revealed deposition of amyloid in the myocardium and Congo Red staining was positive. He suffered from acute infarction of left basal ganglia, resulting from occlusion of the left middle cerebral arterial 6 months prior to admission. However, re-examination of cerebral magnetic resonance imaging in the present hospital revealed an old infarction in the region of the left basal ganglia with a normal appearance of the left middle cerebral artery. Transesophageal echocardiography (TEE) and cardiac magnetic resonance (CMR) both discovered intra-cardiac thrombi, confirming the diagnosis of cardiogenic cerebral embolism. The present study indicates that patients with CA may additionally present with cardiogenic cerebral embolism, and TEE and CMR imaging may help to avoid missing the presence of intra-cardiac thrombi.

Design, Synthesis, and Antitumor Activity of (E,Z)-1-(dihydrobenzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propen-1-ones.

A series of (E,Z)-1-(dihydrobenzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propen-1-ones (C1-C35) were designed and synthesized, and the structures of compounds (Z)-C27 and (Z)-C29 were confirmed by single-crystal X-ray diffraction. The antitumor activities of these novel compounds against cervical cancer (HeLa), lung cancer (A549), and breast cancer (MCF-7) cell lines were evaluated in vitro. Majority of the title compounds exhibited strong antitumor activities and were much more promising than the positive control Taxol, which were also accompanied by lower cytotoxicity to normal cells. In particular, compounds (E,Z)-C24 exhibited the most consistent potent activities against three neoplastic cells with IC50 values ranging from 3.2 to 7.1 µm. Further researches demonstrated that compounds (E,Z)-C24 could induce cell apoptosis and arrest cell cycle at the G2/M and S phases. Meanwhile, the structure-activity relationship between the configurations and cytotoxicity of the compounds was also investigated.

Association between the ABCA1-565C/T gene promoter polymorphism and coronary heart disease severity and cholesterol efflux in the Chinese Han population.

BACKGROUND: ABCA1 -565C/T gene promoter variants have been associated with the severity of coronary artery disease in Western populations. The purpose of our study was to investigate the association between the -565C/T gene polymorphism and coronary artery disease severity and cholesterol efflux in the Chinese Han population. METHODS: A cohort of 298 acute coronary syndrome (ACS) patients and 541 healthy controls was genotyped using the highly sensitive ligase detection reaction. ABCA1 -565C/T genotype was correlated with the clinical features of 164 acute myocardial infarction (AMI) patients. Monocytes from patients with various -565C/T gene polymorphisms were isolated and differentiated into foam cells by coincubation with [(3)H]-labeled acetyl-low-density lipoprotein cholesterol. ABCA1 mRNA and protein expression levels were evaluated, as well as cellular cholesterol efflux. RESULTS: The frequency of the TT genotype in the -565C/T polymorphism of ACS patients was significantly increased when compared with controls (0.211 vs. 0.162, p<0.05). The TT genotype, but not the CT or CC genotypes, in the -565C/T gene polymorphism correlated with the severity of the coronary lesion observed in AMI patients. Patients with the TT homozygote genotype also exhibited significantly lower cellular cholesterol efflux (TT [6.37%±0.554%]) levels than controls and also had the lowest levels of ABCA1 mRNA and protein expression among the group of variants. In contrast, cholesterol efflux levels in AMI patients with CT [11.35%±3.975%] and CC ([15.32%±6.293%]) genotypes were not significantly different from controls. CONCLUSIONS: Impaired ABCA1-mediated cholesterol efflux in macrophages may be associated with the severity of the coronary lesions in AMI patients with the TT genotype at the -565C/T gene polymorphism.

The implication of cigarette smoking and cessation on macrophage cholesterol efflux in coronary artery disease patients.

We investigated ATP-binding cassette transporters A1/G1 expression and function in mediating cholesterol efflux by examining the macrophages of cigarette-smoking patients with coronary artery disease (CAD) before and after smoking abstinence. Peripheral blood monocyte cells were collected from nonsmokers (n = 17), non-CAD (NCAD) smokers (n = 35), and CAD smokers (n = 32) before and after 3 months of smoking cessation. We found that the ABCA1 expression level was lower in macrophages from NCAD and CAD smokers than from nonsmokers at baseline. The ABCA1 function of mediating cholesterol efflux was reduced in NCAD and CAD smokers as compared with nonsmokers. After 3 months of smoking cessation, ABCA1 expression and function were improved in CAD smokers. However, ABCG1 expression and function did not change after smoking cessation. Furthermore, ABCA1 expression was inhibited by tar in human acute monocytic leukemia cell line THP-1-derived macrophages through the inhibition of liver X receptors. Nicotine and carbon monoxide did not inhibit ABCA1 expression. Our results indicate that chronic cigarette smoking impaired ABCA1-mediated cholesterol efflux in macrophages and that tobacco abstinence reversed the function and expression of ABCA1, especially in CAD patients. It was tobacco tar, rather than nicotine or carbon monoxide, that played a major role in the tobacco-induced disturbance of cellular cholesterol homeostasis.

Attenuated macrophage cholesterol efflux function in patients with obstructive sleep apnea-hypopnea syndrome.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is associated with premature atherosclerosis. However, the associated mechanism remains unknown. This study investigates the expression of adenosine triphosphate (ATP)-binding cassette transporter protein A1 (ABCA1) and cellular cholesterol efflux in cultured macrophages from OSAHS patients. METHODS: Of the 18 subjects enrolled in this study, six subjects with apnea-hypopnea index (AHI) <5 were placed into the control group, and 12 subjects with AHI ≥5 were placed into the OSAHS group. Peripheral blood mononuclear cells (PBMCs) from each subject were isolated, purified, cultured, and differentiated into macrophages in vitro. ABCA1 mRNA and protein expression were evaluated by reverse transcription PCR and Western Blot, respectively. Both ABCA1-mediated and autologous serum induced cholesterol efflux were measured by isotopic cholesterol efflux assays. RESULTS: The levels of AHI and high sensitivity C-reactive protein (hsCRP) were significantly higher in the OSAHS group than in the control group. ABCA1 mRNA and protein expressions in PBMCs-derived macrophages were significantly reduced in patients with OSAHS compared to that in controls (p < 0.05). Both ABCA1-mediated and autologous serum-induced cholesterol efflux were significantly lower in the OSAHS group than that in the control group (p = 0.033 and p = 0.01, respectively). Pearson's correlation analysis revealed a negative correlation between AHI and the mRNA (r = -0.7726, p = 0.0007) and protein (r = -0.8112, p = 0.0044) expression of ABCA1, a positive correlation between ABCA1-mediated cholesterol efflux and the minimum oxygen saturation (r = 0.7954, p < 0.0001), and a negative correlation between AHI and autologous serum induced cholesterol efflux (r = -0.7756, p = 0.0002). CONCLUSION: ABCA1 expression and cellular cholesterol efflux in macrophages were significantly decreased in OSAHS patients, which closely correlated with the severity of disease. Our findings provide meaningful insights into the mechanism of atherogenesis in OSAHS patients.

ABCG1 rs57137919G>a polymorphism is functionally associated with varying gene expression and apoptosis of macrophages.

ATP-binding cassette transporter G1 (ABCG1) is a transmembrane cholesterol transporter involved in macrophage sterol homeostasis, reverse cholesterol transport (RCT), and atherosclerosis. The role of ABCG1 in atherosclerosis remains controversial, especially in animal models. Our previous study showed that single nucleotide polymorphism rs57137919 (-367G>A) in the ABCG1 promoter region was associated with reduced risk for atherosclerotic coronary artery disease (CAD). This study was designed to provide functional evidence for the role of rs57137919G>A in atherosclerosis in humans. We combined in vitro and ex vivo studies using cell lines and human monocyte-derived macrophages to investigate the functional consequences of the promoter polymorphism by observing the effects of the rs57137919A allele on promoter activity, transcription factor binding, gene expression, cholesterol efflux, and apoptosis levels. The results showed that the rs57137919A allele was significantly associated with decreased ABCG1 gene expression possibly due to the impaired ability of protein-DNA binding. ABCG1-mediated cholesterol efflux decreased by 23% with rs57137919 A/A versus the G/G genotype. Cholesterol-loaded macrophage apoptosis was induced 2-fold with the A/A genotype compared with the G/G genotype. Proapoptotic genes Bok and Bid mRNA levels were significantly increased in macrophages from the A/A genotype compared with those from the G/G genotype. These findings demonstrated that the ABCG1 promoter rs57137919G>A variant had an allele-specific effect on ABCG1 expression and was associated with an increased apoptosis in cholesterol-loaded macrophages, providing functional evidence to explain the reduced risk for atherosclerosis in subjects with the ABCG1 promoter rs57137919A allele as reported in our previous study.

Valsartan and telmisartan abrogate angiotensin II-induced downregulation of ABCA1 expression via AT1 receptor, rather than AT2 receptor or PPARγ activation.

The possible pharmacological mechanism by which partial PPARγ-activating angiotensin II (Ang II) type 1 receptor blocker (ARB) telmisartan and non-PPARγ-activating ARB valsartan reverse Ang II-suppressed ABCA1 expression is still unclear. In this study, human monocyte-derived THP-1 cells were differentiated into macrophages. Cells were treated with various concentrations of Ang II alone or with Ang II and various drugs including highly selective ARB valsartan, partial PPARγ-activating ARB telmisartan, angiotensin II type 2 (AT2) receptor blocker PD123319, full PPARγ agonist pioglitazone, and PPARγ antagonist GW9662, respectively. After treatment, messenger RNA and protein expressions of ABCA1 and ABCG1 were analyzed by real-time polymerase chain reaction and Western blotting, respectively. ABCA1 expression was remarkably suppressed by Ang II at both messenger RNA and protein levels in a dose-dependent manner in THP-1-derived macrophages, whereas ABCG1 expression was not affected. Valsartan and telmisartan could both reverse the downregulation of Ang II on ABCA1 expression. Such effects were not affected by either AT2 receptor blocker PD123319 or PPARγ antagonist GW9662. Our findings suggest that the effect of Ang II on ABCA1 expression should be mediated by the AT1 receptor. Both valsartan and telmisartan abrogate Ang II-induced downregulation of ABCA1 expression mainly through AT1 receptor rather than through AT2 receptor or PPARγ-dependent pathway.

A polymorphism in the ABCG1 promoter is functionally associated with coronary artery disease in a Chinese Han population.

OBJECTIVE: In this study, we examine the association of single nucleotide polymorphisms (SNPs) of the human ATP binding cassette transporter G1 (ABCG1) gene with atherosclerotic coronary artery disease (CAD) in a Chinese Han population. METHODS: 1021 patients with CAD and 1013 unaffected control subjects were enrolled. PCR-based ligation detection reaction (PCR-LDR) method was used to genotype four SNPs of ABCG1, three (rs2234714, rs2234715 and rs57137919) in the promoter region and one (rs1044317) in the 3'-untranslated region (UTR). RESULTS: The human ABCG1 -367G>A polymorphism (rs57137919) showed a significantly decreased risk for CAD and myocardial infarction (MI) in a dominant model (adjusted OR = 0.73, p = 0.033 for CAD, and adjusted OR = 0.65, p = 0.014 for MI, respectively). The rs57137919 also showed an association with angiographic severity of CAD (multi-vessel vs. single-vessel CAD, adjusted OR = 0.40, p = 0.005). The findings were further supported by luciferase reporter assay, in which the polymorphism impaired reporter gene expression. The ABCG1 -768G>A polymorphism (rs2234714) showed an association with CAD in a recessive model (adjusted OR = 0.64, p = 0.015), but did not demonstrate a functional influence on reporter gene expression in the luciferase reporter assay. CONCLUSIONS: The SNP rs57137919 in the ABCG1 promoter region is functionally associated with a reduced risk of CAD in a Chinese Han population.

Laparoscopic gastric resection approaches for gastrointestinal stromal tumors of stomach.

PURPOSE: To evaluate laparoscopic gastric resection for gastrointestinal stromal tumors (GIST). METHODS: From June, 2003 to October, 2009, 56 patients with gastric GIST who underwent laparoscopic gastric resection were retrospectively reviewed, and their surgical procedure, perioperative outcomes, pathology, and follow-up outcomes were analyzed. RESULTS: All patients underwent laparoscopic gastric resection successfully, including 33 laparoscopic wedge resections, 19 laparoscopic transgastric tumor-everting resections, 3 laparoscopic-assisted distal gastrectomies, and 1 laparoscopic-assisted endoscopic resection. The operative approaches performed were mostly based on the tumor location. No conversions were observed. The mean operative duration was 90 minutes (30 to 210 min), blood loss was 55 mL (5 to 180 mL), time for passage of flatus was 2 days (1 to 11 d), and the postoperative hospital stay was 7 days (3 to 13 d). The resection margin was microscopic negative. After 21.5 months (6 to 76 mo) of follow-up, there was no operative recurrence and metastasis. CONCLUSIONS: Laparoscopic gastric resection for selective cases of gastric GISTs is safe, feasible, and effective. Laparoscopic wedge resection procedure is the first choice for most GISTs located in fundus and anterior wall, laparoscopic transgastric tumor-everting resection procedure can be used in cases with the tumor located in esophagogastric junction area and in posterior wall of the stomach as well. For antral tumors, laparoscopic subtotal gastrectomy with gastrojejunostomy should be performed.

[Cardiovascular manifestations in Chinese patients with hypereosinophilic syndrome].

OBJECTIVE: To evaluate the cardiovascular involvements in Chinese patients with hypereosinophilic syndrome. METHOD: We respectively reviewed 149 inpatients with hypereosinophilic syndrome admitted to Peking Union Medical College Hospital and analyzed the cardiovascular involvements in these patients. RESULTS: Cardiac abnormalities was evidenced in 32.9% patients (49/149). The ratio of male vs female was 34:15. The average age of the patients was (41.3 ± 16.9) years and course of disease was (26.4 ± 72.3) months. Cardiovascular involvements included ST segment and/or T wave (ST-T) ischemic changes, arrhythmia, myocardial injury, cardiac thrombosis, pericardial effusion, pulmonary hypertension, valve disorder, vein or artery thrombosis. After glucocorticoid and/or chemotherapeutic agents and treatment for symptoms, 11 (22.4%) patients achieved remission but have recurrent attacks and 3 (6.1%) patients died from failure in treatment. The prognosis in patients with echocardiogram abnormalities were poorer than those only with electrocardiogram abnormalities (P < 0.05). CONCLUSIONS: Cardiovascular involvements are common in patients with hypereosinophilic syndrome and the manifestation of these involvement is various. Cardiovascular complications of HES are a major source of morbidity and mortality in these disorders.

Laparoscopic treatment for small intestinal bleeding: a report of 77 cases.

BACKGROUND: Morbidity of small intestinal disease is rare and the associated lesion is hard to be detected due to lack of specific manifestations and effective diagnostic approaches. Hematochezia and melena are the most common symptoms in small intestinal diseases. Hence, small intestinal disease is an important differential diagnosis when hematochezia or melena occurs, especially when gastric and colonic diseases are excluded. As the small intestinal lesion is hard to be located preoperatively, laparotomy used to be performed without a preoperative location. This might lead to related postoperative complications. With the development of laparoscopic technique, laparoscopic operations are more frequently applied to surgical disease, despite their benign or malignant nature. Generally, almost all kinds of small intestinal disease can be treated with laparoscopic surgery. METHODS: Clinical data of 77 patients with small intestinal bleeding undergoing laparoscopic or laparoscopy-assisted operations from April 2003 to December 2008 were included, and their clinical information were analyzed retrospectively. RESULTS: No intraoperative complication or conversion was observed in all cases. The mean operative time, mean estimated blood loss, and mean size of incision were 78.3 +/- 30.5 minutes, 17.5 +/- 9.8 mL, and 3.3 +/- 1.9 cm, respectively. Postoperative complications occurred in 4 patients, including 2 cases of adhesive ileus, 1 case of gastric retention, and 1 case of anastomotic bleeding. All of them were cured by nonoperative management. The mean flatus time was 2 days after operation and the mean postoperative hospital stay was 7 days. There was 1 case of gastrointestinal stromal tumor with local recurrence and hepatic metastasis. Four patients died from metastasis of malignant tumors during the follow-up from 2 to 70 months after operations. No trocar site or wound recurrences were noted. CONCLUSIONS: Laparoscopic treatment in small intestinal bleeding is feasible, safe, and minimally invasive. It may be widely used in the future for its good therapeutic outcomes and improved diagnostic chance in small intestinal bleeding diseases.

[Clinical manifestations of premenopausal women with coronary arterial disease].

OBJECTIVE: To compare clinical characteristics among premenopausal women with coronary arterial disease (CAD) with or without atherosclerosis (AS) and postmenopausal women with CAD. METHODS: The clinical and coronary angiographic data, traditional risk factors (age, smoking, blood pressure, lipid profile, blood glucose, BMI, family history) were compared among premenopause (Pre-M, n=42) and post-menopause (Post-M, n=172) women with CAD as well as Pre-M patients with non-AS CAD (non-AS CAD, n=8). RESULTS: Compared with the Post-M patients with CAD, Pre-M CAD patients had significantly fewer traditional risk factors, such as hypertension, diabetes and hypercholesterolemia, significantly more acute coronary syndrome and fewer previous history of chest pain, significantly more single vessel lesion and lower Gessini score (all P < 0. 01). The logistic regression results showed that obesity is an independent risk factor for the development of CAD in premenopausal women (OR = 3. 655, 95% CI: 1. 5-11.59, P = 0.028). Hypertension (OR = 4.73, 95% CI: 0.991-22.589, P = 0.051) and hypercholesterolemia (OR = 4.68, 95% CI: 0.971-22.564, P = 0.055) might also contribute to the development of CAD in these patients. Clinical characteristics were similar between Pre-M and non-AS CAD patients (P > 0.05). CONCLUSIONS: Pre-M CAD patients had less traditional risk factors and lower coronary lesion score compared to post-M CAD patients. Obesity is an independent risk factor for Pre-M CAD. Non-AS coronary artery disease is also an important reason for the development of coronary arterial events in premenopausal women.

[Ten cases analysis of small vessel vasculitis with myocardial involvement].

OBJECTIVE: This study was designed to investigate the clinical characteristics of systemic vasculitis with cardiac involvement. METHODS: Clinical information of 10 patients with systemic vasculitis complicated by myocardial vasculitis, selected from 181 small vessel vasculitis patients and 114 systemic vasculitis patients were analyzed. RESULTS: The clinical manifestations were varied significantly dependent on the etiology of small vessel vasculitis. It is usually difficult to make the diagnosis because of the insidious onset, varied etiology and the undifferentiated manifestations of heart involvement. Echocardiography is commonly used in detecting and monitoring cardiac involvement. Glucocorticoid therapy can improve left ventricular systolic function dramatically when used properly. CONCLUSIONS: The cardiac involvement of systemic vasculitis is quite rare. Dyspnea of various degrees and left ventricular systolic dysfunction are the most common clinical findings. The earlier the establishment of diagnosis and institution of appropriate treatment, the better the prognosis.

[Clinicopathological manifestations of drug-induced lung injury].

OBJECTIVE: To investigate the clinicopathological features of drug-induced lung injury. METHOD: The clinical, radiological and pathological presentations of drug-induced lung injury diagnosed from January 2003 to October 2005 in Peking Union Medical College Hospital were reviewed. RESULTS: There were 7 cases of drug-induced lung injury, 3 caused by amiodarone, and the other 4 caused by interferon-alpha, atorvastatin, carbamazepine, and propylthiouracil respectively. The clinical manifestations included cough, fever, worsening dyspnea and inspiratory crackles. Patchy infiltration, ground-glass attenuation with thickening of bronchovascular markings were the main findings in computed tomography. The most common pathological manifestation was cellular interstitial pneumonia associated with intra-alveolar macrophages with fine vacuolation in the cytoplasm, and type II pneumocyte hyperplasia. The organizing pneumonia pattern was observed in 2 patients. Diffuse alveolar hemorrhage was present in 2 cases. CONCLUSIONS: Drug-induced pulmonary toxicity can be difficult to diagnose. The diagnosis of pulmonary drug toxicity should be considered in patients with a history of drug therapy and new onset or progressive respiratory complaints.

[Diagnosis of coronary artery disease with 99Tcm-N-NOET myocardial perfusion imaging].

OBJECTIVE: To evaluate the sensitivity and specificity of (99)Tc(m)-N-NOET myocardial perfusion tomographic imaging (MPI) for the diagnosis of coronary artery disease (CAD). METHODS: Coronary angiography and (99)Tc(m)-N-NOET myocardial perfusion tomographic imaging were performed in the patients hospitalized in the Department of Cardiology, Peking Union Medical College Hospital, from June to December 2005 with known or suspected diagnosis of CAD. Adenosine was infused intravenously at a rate of 140 microg x kg(-1)min(-1) for 6 minutes. At the third minute of adenosine infusion, 740 MBq (20 mCi) (99)Tc(m)-N-NOET was injected intravenously. MPI was obtained 15 minutes after the (99)Tc(m)-N-NOET infusion. If the result was abnormal, rest myocardial perfusion imaging would be performed 2 hours later. Coronary angiography was performed in all patients within one week after the myocardial perfusion imaging. RESULTS: Myocardial perfusion imaging was performed in 53 cases, 36 males and 17 females, aged 56 +/- 10, who underwent coronary angiography, among which 31 had > or = 50% stenosis of coronary artery and 23 had normal coronary artery. All of the patients with stenosis of coronary artery had positive (99)Tc(m)-N-NOET adenosine stress myocardial perfusion imaging. Nineteen out of the 29 cases without stenosis of coronary artery had negative adenosine myocardial perfusion imaging. The sensitivity and specificity of (99)Tc(m)-N-NOET adenosine myocardial perfusion imaging were 100% and 73% respectively in the detection of stenosis of coronary arteries. Seven cases got percutaneous coronary intervention and 2 got coronary artery bypass graft. Six of the 9 patients undergoing revascularization had stenosis of stents or grafts, 5 of which had positive myocardial perfusion imaging. 3 cases hadn't restenosis and their results of myocardial perfusion imaging were negative. CONCLUSION: (99)Tc(m)-N-NOET myocardial perfusion imaging is a useful non-interventional method for detecting coronary artery stenosis.

[Porcine MSC-derived CLC induced by rabbit's cardiomyocytes extract did not induce immune reaction in vivo].

OBJECTIVE: To compare the in vivo immune reaction of transplanting porcine MSC-derived CLC with rabbit cardiomyocytes extracts induced differentiation or in vitro cultured porcine MSC. METHODS: After injecting the MSC-derived CLC or MSC to the original porcines, the number of CD4+, CD8+ T cells were determined by flow cytometry. The serum concentrations of IL-2, IL-4 were measured by ELISA, and the porcine spleen lymphocyte CTL cytotoxicity was determined by Cell Counting Kit-8 Assay. RESULTS: The numbers of CD4+ and CD8+ T cells, the serum concentrations of IL-2, IL-4 and spleen lymphocyte CTL cytotoxicity were all similar in porcines received MSC-derived CLC induced by rabbit's CMs extract or MSC transplantation. CONCLUSION: The porcine MSC-derived CLC induced by rabbit's CMs extract did not induce extra immune reaction when injected back to the original porcine.

[Differentiation of mesenchymal stem cells into cardio myogenic cells under the induction of myocardial cell lysate].

OBJECTIVE: In order to understand the effects of cardiac microenvironment on the differentiation of bone marrow mesenchymal stem cells (MSCs) into myocardial-like cells, we simulated the cardiac microenvironment in vitro by adding myocardial cell lysate into the culture system of MSCs, and compared the differentiation promoting effect of myocardial cell lysate with that of well-established inducer 5-azacytidine (5-aza). METHODS: Myocardial cells isolated from newly born rats were lysed by repeat freezing and defrosting. MSCs isolated from adult rat were cultured in four different systems. Medium A: medium with myocardial cell lysate; medium B: medium with 5-aza; medium C: medium with 5-aza and myocardial cell lysate; and control medium: ordinary medium without any addition reagent. The dynamic changes of MSCs morphology in different media were observed within 7 days after introduction of MSCs. Immunohistochemical staining against alpha-actin, cTnT, Connexin43 and CD31 were performed at the end of cultivation. RESULTS: MSCs in both medium A and B were differentiated into myocardial-like cells expressing alpha-actin and cTnT after 7-day cultivation. Cells in medium A developed more myofilaments than those in medium B, and expressed CD31, whereas cells in medium B did not. MSCs in control medium only expressed alpha-actin. CONCLUSIONS: Myocardial cell lysate is an ideal inducer to differentiate MSCs into myocardial-like cells in vitro. The differentiation promoting effect of myocardial cell lysate is more predominant than that of 5-aza.