Effect of High-Dose Statin Therapy on Drug-Eluting Stent Strut Coverage.

OBJECTIVE: The influence of high-dose statin therapy on the serial stent healing process has not been fully investigated. Using optical coherence tomography, the effect of high-dose statin therapy on stent strut coverage was evaluated in drug-eluting stent-treated patients. APPROACH AND RESULTS: Sixty patients were randomly assigned to 2 groups according to the statin dose (atorvastatin 40 mg as high-dose statin therapy [n=29] versus pravastatin 20 mg as low-dose statin therapy [n=31]). Serial optical coherence tomographic evaluation post procedure and at the 3-month and 12-month follow-ups was performed in 50 patients with 54 stents (23 atorvastatin-treated patients versus 27 pravastatin-treated patients). The percentage of uncovered struts was defined as the ratio of uncovered struts/total struts. The primary end point was the percentage of uncovered struts at the 12-month follow-up. The secondary end point was the percentage of uncovered struts at the 3-month follow-up and the comparative percentage change (Δ) of uncovered struts at the 3- and 12-month follow-ups between the different dose statin therapies. The percentage of uncovered struts was 7.4% (range, 4.3%-10.4%) in atorvastatin-treated patients versus 10.6% (range, 5.7%-22.6%) in pravastatin-treated patients at the 3-month follow-up (P=0.13) and 1.3% (0.3%-3.8%) versus 2.5% (0.9%-9.7%), respectively, at the 12-month follow-up (P=0.01). The percentage Δ of uncovered struts from 3 to 12 months of follow-up was -7.9±8.5% in atorvastatin-treated patients versus -9.3±12.5% in pravastatin-treated patients (P=0.67). CONCLUSIONS: This study suggested that high-dose statin therapy might provide a beneficial effect for the vascular healing process after drug-eluting stent implantation.

Efficacy of early intensive rosuvastatin therapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (ROSEMARY Study).

The purpose of the study was to investigate whether early high-dose potent statin therapy in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention can reduce infarct size compared with conventional low-dose statin therapy. In a randomized placebo-controlled multicenter trial, 185 patients were assigned either to an early high-dose rosuvastatin group (n = 92, rosuvastatin 40 mg before treatment plus maintenance for 7 days) or to a conventional low-dose rosuvastatin group (n = 93, placebo before treatment plus rosuvastatin 10-mg maintenance for 7 days). Serial cardiac magnetic resonance imaging (MRI) was performed during the acute (3 to 7 days) and chronic (3 months) phases. The primary end point was relative infarct volume assessed by MRI at 3 months. Baseline characteristics were similar between the 2 groups, except hypertension, which was more prevalent in the high-dose group. Serial MRI data were available for 121 patients (high-dose group n = 54 and low-dose group n = 67). The relative infarct volumes in the acute (23.0 ± 9.5% vs 20.5 ± 11.7%, p = 0.208) and chronic (15.9 ± 8.3% vs 15.8 ± 9.7%, p = 0.943) phases were not different between the groups. No differences between groups were observed for periprocedural microvascular circulation evaluated by Thrombolysis In Myocardial Infarction flow grade, myocardial blush grade, ST-segment resolution, microvascular obstruction on cardiac MRI, or clinical outcomes. In conclusion, early high-dose rosuvastatin therapy in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention did not improve periprocedural myocardial perfusion or reduce infarct volume measured by MRI compared with the conventional low-dose rosuvastatin regimen.

A toxicological study of HangAmDan-B in mice.

The aim of the study was to define the toxicity of HangAmDan-B (HAD-B) in mice over the short and long term. HAD-B was studied in 1-week single and 5-week repeated oral dose toxicity tests on male Imprinting Control Region mice. Doses used in 1 week single oral dose toxicity tests were 0, 0.2, 1, 5, and 25 g/kg/day and those of repeated toxicity test were 0, 0.04, 0.2, 1, and 2 g/kg/day. Blood and urine samples were assayed and their morphology observed. Numerical data were compared using Mann-Whitney U test and analysis of variance. Significantly decreased red blood cell levels in mice from S2-HAD-B, S3-HAD-B, S4-HAD-B, and S5-HAD-B groups were observed in single oral dose toxicity tests. Hemoglobin, hematocrit, and mean cell hemoglobin values in mice from the S4-HAD-B and S5-HAD-B groups were also significantly decreased. No mortalities or significant differences in all factors were observed during the dosing period of the repeated dose toxicity test. Administering 2 g/kg/day of HAD-B in mice over a 5-week period showed no significant hematological changes. However, risk of anemia with more than 5 g/kg/ day administration of HAD-B was found. In general, HAD-B appears to be safe and nontoxic, and a no observed adverse effect level in mice was established at 2 g/kg/ day. This data serves as satisfactory preclinical evidence for the safety of HAD-B should a future clinical trial for HAD-B be launched. Further studies are required to confirm these safety results and to carry out a safety trial in humans.

Case series of non-small cell lung cancer treated with mountain Ginseng pharmacopuncture.

This study aims to observe the efficacy of mountain Ginseng (Panax ginseng C.A. Meyer) pharmacopuncture (MGP) on cancer patients using different delivery methods of acupoint injection and intravenous infusion. Six non-small cell lung cancer (NSCLC) patients who met the eligibility criteria were observed. Two patients were continuously infused with MGP (20 mL/day) intravenously, and the other two patients were injected with MGP (10 mL/day) on acupoint LU1 bi-lateral continuously. The remaining two patients received MGP therapy using both methods of delivery. Results were followed by computed tomography (CT) after every cycle; each cycle lasted for 28 days. Two patients infused intravenously showed stable disease and two patients injected on LU1 showed progressive disease. Two patients treated using both methods showed stable disease during the intravenous infusion period and progressive disease during the intraacupuncture injection period. One patient showed progressive disease in the latest chest CT in spite of receiving MGP intravenous infusion. We suggested that MGP may be more effective when used as an intravenous infusion rather than acupoint injection in NSCLC patients.

Chemopreventive effect of Curcuma longa Linn on liver pathology in HBx transgenic mice.

Unlike other forms of hepatocellular carcinoma (HCC), HCC induced by hepatitis B virus (HBV) infection shows a poor prognosis after conventional therapies. HBV induces liver cirrhosis and HCC. Many researchers have made efforts to find new substances that suppress the activity of HBV. Curcuma longa Linn (CLL) has been used for traditional medicine and food in Asia, especially in India, and has shown chemopreventive effects in a HBV-related in vitro model. This in vivo study was designed to seek the chemopreventive effects of CLL and its mechanisms. CLL mixture concentrated with dextrose water by boiling was lyophilized. CLL extracts were administrated to HBV X protein (HBx) transgenic mice aged 4 weeks for 2 to 4 weeks and aged 6 months for 3 months. After administration, histological changes in the liver tissue and expression of HBx-related genes were investigated. CLL-treated mice showed less visceral fat, a smaller liver/body weight ratio and delayed liver pathogenesis. Proliferating cell nuclear antigen (PCNA) expression was also increased in CLL-treated HBx transgenic mice, indicating regeneration of damaged liver tissue. CLL treatment decreased expression of HBx and increased p21 and cyclin D1 in livers of HBx transgenic mice. In addition, p-p53 was increased after CLL treatment. These results suggest that CLL can have beneficial effects on the early and late stages of liver pathogenesis, preventing and delaying liver carcinogenesis. This drug should be considered as a potential chemopreventive agent for HBV-related hepatocarcinogenesis.

Antitumor effect of skin of venenum bufonis in a NCI-H460 tumor regression model.

This experimental study was performed to investigate the antitumor effect of skin of venenum bufonis (SVB) in NCI-H460 human lung cancer cell xenografted nude mice. NCI-H460 cell lines were cultured and then xenografted into nude mice. Mice were divided into four groups: SVB (0.25 mg/kg) given orally, SVB (0.25 mg/kg) interperitoneally, SVB (0.5 mg/kg) interperitoneally, and the untreated group. Mice were raised and treated for 28 days. Body weight and tumor weight and volumes were measured daily. Absolute organ weight, microhistological observations and biochemical blood analyses were performed on the final day of the study following the sacrificing of these animals. Tumor inhibition rate, mean survival time and percent increase in life span were also calculated. Tumor size decreased in all SVB treated mice. Increasing the dose of SVB attenuated the inhibition rate seen on the 11th day of this experiment. Furthermore, tumor weight and volume in the mice treated with the highest dose of SVB were the smallest. Mice treated with high-dose intraperitoneal SVB gained weight and had significantly smaller spleens compared with untreated mice. Mean survival time and percent increase in life span in the low-dose intraperitoneal SVB treatment group were higher than those of other groups. Biochemical blood analysis revealed that phosphatase and urea nitrogen levels were decreased significantly in 0.25 mg/kg SVB orally treated mice (p < 0.01). Blood level calcium and alanine transaminase significantly decreased with intraperitoneal SVB 0.5 mg/kg (p < 0.05). The findings of this in vivo study suggest that SVB may have potential as a tumor growth inhibitor. Further research that overcomes the limitations of this study to determine the antitumor mechanism of SVB is still required.

Efficacy of high-dose atorvastatin loading before primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: the STATIN STEMI trial.

OBJECTIVES: This study sought to determine the efficacy of high-dose atorvastatin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). BACKGROUND: Previous randomized trials have demonstrated that statin pre-treatment reduced major adverse cardiac events (MACEs) in patients with stable angina pectoris and acute coronary syndrome. However, no randomized studies have been carried out with STEMI patients in a primary PCI setting. METHODS: A total 171 patients with STEMI were randomized to 80-mg atorvastatin (n = 86) or 10-mg atorvastatin (n = 85) arms for pre-treatment before PCI. All patients were prescribed clopidogrel (600 mg) before PCI. After PCI, both groups were treated with atorvastatin (10 mg). The primary end point was 30-day incidence of MACE including death, nonfatal MI, and target vessel revascularization. Secondary end points included corrected thrombolysis in myocardial infarction frame count, myocardial blush grade, and ST-segment resolution at 90 min after PCI. RESULTS: MACE occurred in 5 (5.8%) and 9 (10.6%) patients in the 80-mg and 10-mg atorvastatin pre-treatment arms, respectively (p = 0.26). Corrected thrombolysis in myocardial infarction frame count was lower in the 80-mg atorvastatin arm (26.9 +/- 12.3 vs. 34.1 +/- 19.0, p = 0.01). Myocardial blush grade and ST-segment resolution were also higher in the 80-mg atorvastatin arm (2.2 +/- 0.8 vs. 1.9 +/- 0.8, p = 0.02 and 61.8 +/- 26.2 vs. 50.6 +/- 25.8%, p = 0.01). CONCLUSIONS: High-dose atorvastatin pre-treatment before PCI did not show a significant reduction of MACEs compared with low-dose atorvastatin but did show improved immediate coronary flow after primary PCI. High-dose atorvastatin may produce an optimal result for STEMI patients undergoing PCI by improving microvascular myocardial perfusion. (Efficacy of High-Dose AtorvaSTATIN Loading Before Primary Percutaneous Coronary Intervention in ST-Elevation Myocardial Infarction [STATIN STEMI]; NCT00808717).

Toxicity studies on Secretio Bufonis: a traditional supplement in Asia.

OBJECTIVES: This study was performed to investigate the toxicity of Secretio Bufonis (SB) on male mice and assess its no-observed-adverse-effect-level (NOAEL). MATERIALS AND METHODS: After feeding an aqueous solution of SB extracts to mice for either 1 or 8 weeks, their blood and urine were assayed and their liver and kidney morphology examined. The numerical data was analyzed by the Mann-Whitney U-test and analysis of variance test. RESULTS: Mice administered SB in 50 mg/kg/day for 1 week had higher heart weights and higher aspartate transaminase activities; those administered SB in 0.01 and 0.05 mg/kg/day for 8 weeks had lower creatinine concentrations; and those administered SB in 0.5 mg/kg/day for 8 weeks had higher brain weights and higher blood urea nitrogen. CONCLUSIONS: The extracts of SB had cardiac toxicity in the short term and hepatotoxicity in the long term. The NOAEL of the extract was under 5 mg/kg/day for 1 week and under 0.25 mg/kg/day for 8 weeks.

Antitumor activity of water extracts from Cordyceps militaris in NCI-H460 cell xenografted nude mice.

This experimental study investigated the antitumor effect of Cordyceps militaris in NCI-H406 cell transplanted nude mice. After feeding an aqueous solution of C. militaris extracts in NCI-H460 cell xenografted nude mice for 4 weeks, we measured the size of a tumor mass and calculated the inhibition rate. We also estimated survival time and calculated mean survival time and percent increase in lifespan. Results showed that the inhibition rate of water extract of the 150 mg/kg/day C. militaris-administered group was 94.73-75.08% and that of the 300 mg/kg/day C. militaris-administered group was 85.81-73.81%. The tumor weights and volumes decreased in a dose-dependent manner. Mean survival time of the 150 mg/kg/day C. militaris-administered group was extended to 19.43 +/- 2.44 days and 5.42% increased in lifespan (ILS) and that of the 300 mg/kg/day C. militaris-administered group was 21.86 +/- 3.53 days and 18.61% ILS. The relative liver weight was significantly increased in 300 mg/kg/day C. militaris-administered group, but there was no histopathological difference. In conclusion, C. militaris, shrunk tumors and increased mouse lifespan, suggesting that C. militaris was effective in treating tumors in nude mice.

Anti-inflammatory activity of Schizonepeta tenuifolia through the inhibition of MAPK phosphorylation in mouse peritoneal macrophages.

Schizonepeta tenuifolia (ST) is a well-known herb to treat the cold and its associated headache. However, the anti-inflammatory mechanism of ST in mouse peritoneal macrophages is not clear. In this study, we demonstrated that ST inhibited lipopolysaccaride (LPS)-induced tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 production. The maximal inhibition rate of TNF-alpha and IL-6 production by ST (2 mg/ml) was 48.01 +/- 2.8% and 56.45 +/- 2.8%, respectively. During the inflammatory process, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) were increased in mouse peritoneal macrophages. However, treated with ST decreased the protein level of COX-2 and iNOS, as well as the production of PGE(2) and NO in LPS-stimulated mouse peritoneal macrophages. In addition, ST inhibited the phosphorylation of MAPK. Taken together, the results of this study suggest an important molecular mechanism by which ST reduces inflammation, which may explain its beneficial effect in the regulation of inflammatory reactions.

Hirschsprung disease and hypoganglionosis in adults: radiologic findings and differentiation.

PURPOSE: To retrospectively evaluate the imaging features of adult Hirschsprung disease (HD) and adult hypoganglionosis (HG) and to compare these features with histopathologic findings. MATERIALS AND METHODS: This study was institutional review board approved, and the requirement for informed consent was waived. The imaging, medical, and histopathologic data of 10 patients (seven women, three men; mean age, 38 years) with histopathologically proved adult HD and/or adult HG were reviewed. Two radiologists reviewed 10 transverse computed tomographic (CT) scans and five double-contrast barium enema radiographs in consensus for the presence or absence and the location of the transition zone. The transverse diameter ratio of the most dilated colonic segment proximal to the transition zone to the narrowed colonic segment distal to the transition zone (ie, transition zone ratio), and the longitudinal length of the transition zone were also determined. The CT findings of HD and HG were compared by using the Mann-Whitney U test. RESULTS: All patients with lifelong or chronic constipation had a transition zone in the upper part of the rectum or rectosigmoid junction (n = 5) or in the descending colon (n = 5) on the CT scans and the double-contrast barium enema radiographs. The transition zone ratio was significantly different between the patients with HD (median ratio, 4.0) and the patients with HG (median ratio, 2.0) (P = .016). However, there was no significant difference in the longitudinal length of the transition zone between the two patient groups (median ratios, 4.4 cm for HD group and 6.0 cm for HG group; P = .190). CONCLUSION: A markedly dilated proximal colonic segment with a transition zone and a narrowed distal colonic segment on CT and double-contrast barium enema images in conjunction with chronic refractory constipation in an adult should suggest the diagnosis of adult HD or adult HG. The detection of a much higher transition zone ratio may help to establish the diagnosis of HD.

[New trends of medicine manifested at Naeuiwon in the late Chosun period].

Tonifying method has been used to treat various types of deficiency syndrome in traditional Korean medicine. Tonifying medicinal including ginseng and deer horns is one of the various methods of the treatments, but they are recognized as a representative of traditional Korean remedies nowadays in Korea. That is concerned with the new trends of medicine manifested at Naeuiwon (Royal Infirmary) in the late Chosun period. The period that manifested the tonifying method obviously was the reign of King Youngjo (r.1724-1776). King Youngjo who lived longest among Chosun kings considered tonifying yang very important in keeping him healthy. He had taken a large quantity of ginseng, he and others considered the reason for his longevity as taking ginseng. From that time, the method of tonifying yang became one of the principles in health care and treatment as well. In the 19th century, the theory of tonifying method had been changed, in that tonifying yin was considered more important among Naeuiwon physicians. Tonifying yang alone was thought to be harmful because of its warm and dry nature. The main cause of prevalence of tonifying method in Naeuiwon was the fact that it was safe and had little side effects. The method of health care and treatments of the kings was considered as an ideal model by the ordinary people at that time. The new trends of medicine manifested at Naeuiwon in the late Chosun period had a strong influence on traditional Korean medicine, which emphasized the importance of tonifying method.