Rationale of decreasing low-density lipoprotein cholesterol below 70 mg/dL in patients with coronary artery disease: A retrospective virtual histology-intravascular ultrasound study

Background: The associations between statin and coronary plaque compositional changes were re­ported according to the use of high dose or not. An evaluation of the impact of low-density lipoprotein cholesterol (LDL-C) < 70 mg/dL by using real world dosages of statin on coronary plaque composition was undertaken. Methods: The study subjects consisted of 61 patients (mean 59.9 years old, 45 males) who underwent percutaneous coronary intervention, baseline and follow-up (F/U; mean 8.4 months) virtual histology- -intravascular ultrasound (VH-IVUS) examination. Change of plaque composition at peri-stent area, which was selected in order to measure the identical site at F/U study, was compared according to the F/U LDL-C level. Results: Body mass index, prevalence of dyslipidemia, baseline total cholesterol and baseline LDL-C were significantly lower in F/U LDL-C < 70 mg/dL group (14 segments in 10 patients) than F/U LDL-C ≥ 70 mg/dL group (79 segments in 51 patients). F/U high-density lipoprotein cholesterol (HDL-C, OR 1.06, 95% CI 1.00–1.11, p = 0.054) and F/U LDL-C < 70 mg/dL (OR 3.43, 95% CI 0.97–12.17, p = 0.056) showed strong tendency of regression of necrotic core volume (NCV) ≥ 10%. In multivariable logis­tic regression analysis, F/U HDL-C (OR 1.07, 95% CI 1.01–1.14, p = 0.020) and F/U LDL-C < 70 mg/dL (OR 8.02, 95% CI 1.58–40.68, p = 0.012) were the independent factors for regression of NCV ≥ 10%. Conclusions: Follow-up LDL-C level < 70 mg/dL with any types of statins and increase of HDL-C were associated with regression of NCV ≥ 10% in patients with coronary artery disease

Bioassays of Compounds with Potential Juvenoid Activity on \u3ci\u3eDrosophila melanogaster\u3c/i\u3e: Juvenile Hormone III, Bisepoxide Juvenile Hormone III, and Methyl Farnesoates

Metabolites of the 6,7,10,11 bisepoxide juvenile hormone III (JHB3), and other potential juvenoids, were tested for juvenile hormone activity using early instar or early stage pupae of Drosophila mela-nogaster. Importantly, methyl farnesoates were tested as they might have JH-like activity on Dipteran juveniles. Larvae were exposed to compounds in medium, or the compounds were applied to white puparia. In the assays employed in the present study, there was no indication for JH activity associ-ated with the metabolites of JHB3. The activity of methyl farnesoate (MF) was higher than that of JH III and far greater than bisepoxide JH III. As opposed to the two endogenous juvenile hormones, methyl farnesoate has weak activity in the white puparial bioassay. When fluorinated forms of me-thyl farnesoate, which is unlikely to be converted to JH, were applied to Drosophila medium to which fly eggs were introduced, there was a high degree of larval mortality, but no evidence of subsequent mortality at the pupal stage. One possible explanation for the results is that methyl farnesoate is active as a hormone in larval stages, but has little activity at the pupal stage where only juvenile hormone has a major effect

Bioassays of Compounds with Potential Juvenoid Activity on \u3ci\u3eDrosophila melanogaster\u3c/i\u3e: Juvenile Hormone III, Bisepoxide Juvenile Hormone III, and Methyl Farnesoates

Metabolites of the 6,7,10,11 bisepoxide juvenile hormone III (JHB3), and other potential juvenoids, were tested for juvenile hormone activity using early instar or early stage pupae of Drosophila mela-nogaster. Importantly, methyl farnesoates were tested as they might have JH-like activity on Dipteran juveniles. Larvae were exposed to compounds in medium, or the compounds were applied to white puparia. In the assays employed in the present study, there was no indication for JH activity associ-ated with the metabolites of JHB3. The activity of methyl farnesoate (MF) was higher than that of JH III and far greater than bisepoxide JH III. As opposed to the two endogenous juvenile hormones, methyl farnesoate has weak activity in the white puparial bioassay. When fluorinated forms of me-thyl farnesoate, which is unlikely to be converted to JH, were applied to Drosophila medium to which fly eggs were introduced, there was a high degree of larval mortality, but no evidence of subsequent mortality at the pupal stage. One possible explanation for the results is that methyl farnesoate is active as a hormone in larval stages, but has little activity at the pupal stage where only juvenile hormone has a major effect

In-stent restenosis-prone coronary plaque composition: A retrospective virtual histology-intravascular ultrasound study

  Background: The mechanism of in-stent restenosis (ISR) is multifactorial, which includes biological, mechanical and technical factors. This study hypothesized that increased inflammatory reaction, which is known to be an important atherosclerotic process, at a culprit lesion may lead to higher restenosis rates. Methods: The study population consisted of 241 patients who had undergone percutaneous coronary intervention with virtual histology-intravascular ultrasound (VH-IVUS) and a 9-month follow-up coronary angiography. Compared herein is the coronary plaque composition between patients with ISR and those without ISR. Results: Patients with ISR (n = 27) were likely to be older (66.2 ± 9.5 years vs. 58.7 ± 11.7 years, p = 0.002) and have higher levels of high-sensitivity C-reactive protein (hs-CRP, 1.60 ± 3.59 mg/dL vs. 0.31 ± 0.76 mg/dL, p < 0.001) than those without ISR (n = 214). VH-IVUS examination showed that percent necrotic core volume (14.3 ± 8.7% vs. 19.5 ± 9.1%, p = 0.005) was higher in those without ISR than those with ISR. Multivariate analysis revealed that hs-CRP (odds ratio [OR] 3.334, 95% con­fidence interval [CI] 1.158–9.596, p = 0.026) and age (OR 3.557, 95% CI 1.242–10.192, p = 0.018) were associated with ISR. Conclusions: This study suggests that ISR is not associated with baseline coronary plaque composition but is associated with old age and increased expression of the inflammatory marker of hs-CRP. (Cardiol J 2018; 25, 1: 7–13

Subchronic inhalation toxicity of gold nanoparticles

<p>Abstract</p> <p>Background</p> <p>Gold nanoparticles are widely used in consumer products, including cosmetics, food packaging, beverages, toothpaste, automobiles, and lubricants. With this increase in consumer products containing gold nanoparticles, the potential for worker exposure to gold nanoparticles will also increase. Only a few studies have produced data on the <it>in vivo </it>toxicology of gold nanoparticles, meaning that the absorption, distribution, metabolism, and excretion (ADME) of gold nanoparticles remain unclear.</p> <p>Results</p> <p>The toxicity of gold nanoparticles was studied in Sprague Dawley rats by inhalation. Seven-week-old rats, weighing approximately 200 g (males) and 145 g (females), were divided into 4 groups (10 rats in each group): fresh-air control, low-dose (2.36 × 10⁴particle/cm³, 0.04 μg/m³), middle-dose (2.36 × 10⁵particle/cm³, 0.38 μg/m³), and high-dose (1.85 × 10⁶particle/cm³, 20.02 μg/m³). The animals were exposed to gold nanoparticles (average diameter 4-5 nm) for 6 hours/day, 5 days/week, for 90-days in a whole-body inhalation chamber. In addition to mortality and clinical observations, body weight, food consumption, and lung function were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry tests, and organ weights were measured. Cellular differential counts and cytotoxicity measurements, such as albumin, lactate dehydrogenase (LDH), and total protein were also monitored in a cellular bronchoalveolar lavage (BAL) fluid. Among lung function test measurements, tidal volume and minute volume showed a tendency to decrease comparing control and dose groups during the 90-days of exposure. Although no statistically significant differences were found in cellular differential counts, histopathologic examination showed minimal alveoli, an inflammatory infiltrate with a mixed cell type, and increased macrophages in the high-dose rats. Tissue distribution of gold nanoparticles showed a dose-dependent accumulation of gold in only lungs and kidneys with a gender-related difference in gold nanoparticles content in kidneys.</p> <p>Conclusions</p> <p>Lungs were the only organ in which there were dose-related changes in both male and female rats. Changes observed in lung histopathology and function in high-dose animals indicate that the highest concentration (20 μg/m³) is a LOAEL and the middle concentration (0.38 μg/m³) is a NOAEL for this study.</p

Comparison of angiographic patterns of in-stent restenosis between sirolimus-and paclitaxel-eluting stent

Abstract Background: Angiographic pattern of in-stent restenosis (ISR) after drug-eluting stent (DES) implantation was known to be different to that after bare metal stent (BMS) implantation. But the different angiographic patterns of ISR and its prognosis between sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES) has not been properly addressed in large scale studies. Results: In angiographic ISR pattern, diffuse ISR was more common in PES implantation (SES vs PES; 23.7% vs 48.7%, p = 0.001) mainly because of higher incidence of diffuse intrastent ISR (8.2% vs 33.8%, p b 0.001, respectively) whereas focal ISR was more common in SES implantation (76.3% vs 51.3%, p = 0.001, respectively) mainly because of higher incidence of focal margin ISR (27.8% vs 2.5%, p b 0.001, respectively). Among 177 ISR lesions, clinically driven target lesion revascularization (TLR) was performed in 53.6% in SES implantation and 56.3% in PES implantation ( p = 0.725). Conclusion: Angiographic pattern of ISR differed after SES and PES implantation, but their subsequent TLR rate was similar to both types of DES

Initial Biopsy Outcome Prediction in Korean Patients-Comparison of a Noble Web-based Korean Prostate Cancer Risk Calculator versus Prostate-specific Antigen Testing

We developed and validated a novel Korean prostate cancer risk calculator (KPCRC) for predicting the probability of a positive initial prostate biopsy in a Korean population. Data were collected from 602 Koreans who underwent initial prostate biopsies due to an increased level of prostate-specific antigen (PSA), a palpable nodule upon digital rectal examination (DRE), or a hypoechoic lesion upon transrectal ultrasound (TRUS). The clinical and laboratory variables were analyzed by simple and multiple logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was computed to compare its performance to PSA testing alone. Prostate cancer was detected in 172 (28.6%) men. Independent predictors included age, DRE findings, PSA level, and prostate transitional zone volume. We developed the KPCRC using these variables. The AUC for the selected model was 0.91, and that of PSA testing alone was 0.83 (P < 0.001). The AUC for the selected model with an additional dataset was 0.79, and that of PSA testing alone was 0.73 (P = 0.004). The calculator is available on the website: http://pcrc.korea.ac.kr. The KPCRC improved the performance of PSA testing alone in predicting the risk of prostate cancer in a Korean population. This calculator would be a practical tool for physicians and patients

Galectin-3 Facilitates Cell Motility in Gastric Cancer by Up-Regulating Protease-Activated Receptor-1(PAR-1) and Matrix Metalloproteinase-1(MMP-1)

BACKGROUND: Galectin-3 is known to regulate cancer metastasis. However, the underlying mechanism has not been defined. Through the DNA microarray studies after galectin-3 silencing, we demonstrated here that galectin-3 plays a key role in up-regulating the expressions of protease-activated receptor-1 (PAR-1) and matrix metalloproteinase-1 (MMP-1) PAR-1 thereby promoting gastric cancer metastasis. METHODOLOGY/PRINCIPAL FINDINGS: We examined the expression levels of Galectin-3, PAR-1, and MMP-1 in gastric cancer patient tissues and also the effects of silencing these proteins with specific siRNAs and of over-expressing them using specific lenti-viral constructs. We also employed zebrafish embryo model for analysis of in vivo gastric cancer cell invasion. These studies demonstrated that: a) galectin-3 silencing decreases the expression of PAR-1. b) galectin-3 over-expression increases cell migration and invasion and this increase can be reversed by PAR-1 silencing, indicating that galectin-3 increases cell migration and invasion via PAR-1 up-regulation. c) galectin-3 directly interacts with AP-1 transcriptional factor, and this complex binds to PAR-1 promoter and drives PAR-1 transcription. d) galectin-3 also amplifies phospho-paxillin, a PAR-1 downstream target, by increasing MMP-1 expression. MMP-1 silencing blocks phospho-paxillin amplification and cell invasion caused by galectin-3 over-expression. e) Silencing of either galectin-3, PAR-1 or MMP-1 significantly reduced cell migration into the vessels in zebrafish embryo model. f) Galectin-3, PAR-1, and MMP-1 are highly expressed and co-localized in malignant tissues from gastric cancer patients. CONCLUSIONS/SIGNIFICANCE: Galectin-3 plays the key role of activating cell surface receptor through production of protease and boosts gastric cancer metastasis. Galectin-3 has the potential to serve as a useful pharmacological target for prevention of gastric cancer metastasis

The Mildly Elevated Serum Bilirubin Level is Negatively Associated with the Incidence of End Stage Renal Disease in Patients with IgA Nephropathy

Oxidative stress plays various roles in the development and progression of IgA nephropathy, while bilirubin is known as a potent antioxidant. We therefore hypothesized that serum bilirubin would be associated with renal prognosis in IgA nephropathy. The study subjects comprised 1,458 adult patients with primary IgA nephropathy in Korea. We grouped patients according to the following quartile levels of bilirubin: <0.4 mg/dL (Q1), 0.4-0.5 mg/dL (Q2), 0.6-0.7 mg/dL (Q3), and >0.8 mg/dL (Q4). The outcome data were obtained from the Korean Registry of end-stage renal disease (ESRD). Eighty patients (5.5%) contracted ESRD during a mean follow-up period of 44.9 months. The ESRD incidences were 10.7% in Q1, 8.2% in Q2, 2.8% in Q3, and 2.8% in Q4 (p<0.001). The relative risk of ESRD compared to that in Q1 was 0.307 (95% confidence interval [CI], 0.126-0.751) in Q3 and 0.315 (95% CI, 0.130-0.765) in Q4. The differences of ESRD incidence were greater in subgroups of males and of patients aged 35 yr or more, with serum albumin 4.0 g/dL or more, with normotension, with eGFR 60 mL/min/1.73 m2 or more, and with proteinuria less then 3+ by dipstick test. In conclusion, higher bilirubin level was negatively associated with ESRD incidence in IgA nephropathy