2017 Vol. 31, No. 2
Cholesterol crystal embolic (CCE) syndrome is often a clinically challenging condition that has a poor prognostic implication. It is a result of plaque rupture with release of cholesterol crystals into the circulation that embolize into various tissue organs. Plaque rupture seems to be triggered by an expanding necrotic core during cholesterol crystallization forming sharp tipped crystals that perforate and tear the fibrous cap. Embolizing cholesterol crystals then initiate both local and systemic inflammation that eventually lead to vascular fibrosis and obstruction causing symptoms that can mimic other vasculitic conditions. In fact, animal studies have demonstrated that cholesterol crystals can trigger an inflammatory response via NLRP3 inflammasome similar to that seen with gout. The diagnosis of CCE syndrome often requires a high suspicion of the condition. Serum inflammation biomarkers including elevated sedimentation rate, abnormal renal function tests and eosinophilia are useful but non-specific. Common target organ involvement includes the skin, kidney, and brain. Various testing including fundoscopic eye examination and other non-invasive procedures such as trans-esophageal echocardiography and magnetic resonance imaging may be helpful in identifying the embolic source. Treatment includes aspirin and clopidogrel, high dose statin and possibly steroids. In rare cases, mechanical intervention using covered stents may help isolate the ruptured plaque. Anticoagulation with warfarin is not recommended and might even be harmful. Overall, CCE syndrome is usually a harbinger of extensive and unstable atherosclerotic disease that is often associated with acute cardiovascular events.
The liver directs cholesterol metabolism in the organism. All the major fluxes of cholesterol within the body involve the liver: dietary cholesterol is directed to the liver; cholesterol from peripheral cells goes to the liver; the liver is a major site of cholesterol synthesis for the organism; cholesterol is secreted from the liver within the bile, within apoB lipoproteins and translocated to nascent HDL. The conventional model of cholesterol homeostasis posits that cholesterol from any source enters a common, rapidly exchangeable pool within the cell, which is in equilibrium with a regulatory pool. Increased influx of cholesterol leads rapidly to decreased synthesis of cholesterol. This model was developed based on in vitro studies in the fibroblast and validated only for LDL particles. The challenges the liver must meet in vivo to achieve cholesterol homeostasis are far more complex. Our model posits that the cholesterol derived from three different lipoproteins endosomes has three different fates: LDL-derived cholesterol is largely recycled within VLDL with most of the cholesterol shunted through the hepatocyte without entering the exchangeable pool of cholesterol; high density lipoprotein-derived CE is transcytosed into bile; and chylomicron remnant-derived cholesterol primarily enters the regulatory pool within the hepatocyte. These endosomal channels represent distinct physiological pathways and hepatic homeostasis represents the net result of the outcomes of these distinct channels. Our model takes into account the distinct physiological challenges the hepatocyte must meet, underlie the pathophysiology of many of the apoB dyslipoproteinemias and account for the sustained effectiveness of therapeutic agents such as statins.
2017, 31(2): 108-115. doi: 10.7555/JBR.31.20150175
It is generally recognized that Caucasians and Asians have different skin aging features. The aim of this study was to develop a facial wrinkle grading scale for Chinese women. Standard photographs were taken of 242 Chinese women. Six sets of 0 to 9 wrinkle scales with reference photographs and descriptions were selected, including grading scales for resting and hyperkinetic crow's feet, frontalis lines, glabellar frown lines, and nasolabial folds. To identify the scale by objective quantitative measurement, skin surface measurements from the Visioscan? VC98 were used. To test the reliability and validity of our wrinkle scale, a multi-rater consensus method was used. A double-blind, randomized, vehicle-controlled 12-week study was conducted to use this clinical photo-score to evaluate the efficacy and safety of Centella triterpenes cream? in treating crow's feet. A newly developed 10-point photographic and descriptive scale emerged from this study. The final atlas of these photographs contained a total of 6 sets with 10 pictures each. From 0 to 9, surface evaluation of smoothness (SEsm) parametric measurements decreased progressively, indicating that the scale increased inversely. Weighted kappa coefficients for intra-assessor were between 0.75-0.87. The overall Kendall's coefficient is 0.86 on the first rating and 0.87 on the second rating. Thirtysix volunteers were recruited and 35 subjects completed a 12-week trial. Clinical photo-score by investigator showed a significant difference (P <0.05) between the treatment side and control side after 4 weeks. Use of these scales in clinical settings to evaluate facial wrinkles in Asians individuals is recommended.
Cholesterol-core nanoparticles (LDE) have been shown to be recognized by low-density lipoprotein receptors (LDLR) after administration; therefore, LDE is an ideal vehicle to deliver drug with targeting property. Paclitaxel, when incorporated into LDE, promotes atherosclerosis regression with reduced drug toxicity in rabbits through LDLR. Here, we tested whether LDE paclitaxel could still be effective in reducing diet-induced atherosclerosis in a mouse model without LDLR. Nineteen LDLR knockout male mice were fed 1% cholesterol for 12 weeks. Then, 12 animals received 4-weekly intraperitoneal LDE-paclitaxel (4 mg/kg) while 7 controls received saline solution. On week 12 and 16, in vivo MRI of the aortic roots was performed. Aorta macroscopy was made after euthanasia. Reduction of atherosclerotic lesions was observed. LDE-paclitaxel treatment resulted in reduction of wall area (14%) and stenosis (22%) by MRI and 33% by macroscopy. Thus, LDE-paclitaxel may produce pharmacological effects through LDE uptake by mechanisms other than LDLR.
Since plant oils are believed to be better than animal fats for cerebrovascular and cardiovascular diseases, the effects of various plant oils and trans-fat on blood lipid profiles and ischemic stroke were investigated. SpragueDawley rats were fed a diet containing the oils or trans-fat, and then body weights, blood lipids, and effects on brain infarction and physical dysfunction induced by middle cerebral artery occlusion (MCAO) were analyzed. All the oils and trans-fat, except perilla oil, significantly increased body fats and body weight gain. Sesame oil and trans-fat specifically increased blood cholesterols and triglycerides, respectively, while perilla oil decreased both cholesterols and triglycerides. Perilla oil not only attenuated cerebral infarction, but also restored locomotor activity and rota-rod performances of MCAO rats. It is suggested that perilla oil among oils and fats could be the first choice to reduce the risk of metabolic syndrome and ischemic stroke.
The International Agency for Research on Cancer and the World Health Organization have designated airborne particulates, including particulates of median aerodynamic diameter ≤ 2.5 μm (PM2.5), as Group 1 carcinogens. It has not been determined, however, whether exposure to ambient PM2.5 is associated with an increase in respiratory related diseases. This meta-analysis assessed the association between exposure to ambient fine particulate matter (PM2.5) and the risk of respiratory tract diseases, using relevant articles extracted from PubMed, Web of Science, and Embase. In results, of the 1,126 articles originally identified, 35 (3.1%) were included in this meta analysis. PM2.5 was found to be associated with respiratory tract diseases. After subdivision by age group, respiratory tract disease, and continent, PM2.5 was strongly associated with respiratory tract diseases in children, in persons with cough, lower respiratory illness, and wheezing, and in individuals from North America, Europe, and Asia. The risk of respiratory tract diseases was greater for exposure to traffic related than non-traffic-related air pollution. In children, the pooled relative risk (RR) represented significant increases in wheezing (8.2%), cough (7.5%), and lower respiratory illness (15.3%). The pooled RRs in children were 1.091 (95%CI: 1.049, 1.135) for exposure to < 25 μg/m3 PM2.5, and 1.126 (95%CI: 1.067, 1.190) for exposure to ≥ 25 μg/m3 PM2.5. In conclusion, exposure to ambient PM2.5 was significantly associated with the development of respiratory tract diseases, especially in children exposed to high concentrations of PM2.5.
Noise has been regarded as an environmental/occupational stressor that causes damages to both auditory and nonauditory organs. Prolonged exposure to these mediators of stress has often resulted in detrimental effect, where oxidative/nitrosative stress plays a major role. Hence, it would be appropriate to examine the possible role of free radicals in brain discrete regions and the "antioxidants" mediated response of S. dulcis. Animals were subjected to noise stress for 15 days (100 dB/4 hours/day) and estimation of endogenous free radical and antioxidant activity were carried out on brain discrete regions (the cerebral cortex, cerebellum, brainstem, striatum, hippocampus and hypothalamus). The result showed that exposure to noise could alleviate endogenous free radical generation and altered antioxidant status in brain discrete regions when compared to that of the control groups. This alleviated free radical generation (H2O2 and NO) is well supported by an upregulated protein expression on immunohistochemistry of both iNOS and nNOS in the cerebral cortex on exposure to noise stress. These findings suggest that increased free radical generation and altered anti-oxidative status can cause redox imbalance in the brain discrete regions. However, free radical scavenging activity of the plant was evident as the noise exposed group treated with S. dulcis[200 mg/(kg $b$w)] displayed a therapeutic effect by decreasing the free radical level and regulate the anti-oxidative status to that of control animals. Hence, it can be concluded that the efficacy of S. dulcis could be attributed to its free radical scavenging activity and anti-oxidative property.
Zeaxanthin is a common carotenoid, which is a powerful antioxidant that protects against damage caused by reactive oxygen species. The aim of the present study was to investigate the effects of zeaxanthin supplementation on in vitro maturation of porcine embryo development. We investigated nuclear maturation, intracellular glutathione (GSH), and reactive oxygen species (ROS) levels during in vitro maturation, and subsequent embryonic development following parthenogenetic activation and in vitro fertilization (IVF). The oocytes were maturated and used at the metaphase II stage. After 42 hours of in vitro maturation, the zeaxanthin-treated group (0.5 mmol/L) showed significant increases in nuclear maturation (89.6%) than the control group (83.4%) (P < 0.05). The intracellular GSH levels increased significantly (P < 0.05) as zeaxanthin concentrations increased; ROS generation levels decreased with increased zeaxanthin concentrations, but there were no significant differences. There were no significant differences in subsequent embryonic development, cleavage rate, blastocyst stage rate, and total blastocyst cell numbers following parthenogenetic activation and IVF when in vitro maturation media was supplemented with zeaxanthin. These results suggest that treatment with zeaxanthin during in vitro maturation improved the nuclear maturation of porcine oocytes by increasing the intracellular GSH level, thereby slightly decreasing the intracellular ROS level.
The aim of this study was to assess sensitivity and responsiveness of power Doppler ultrasound (PDUS) in detecting enthesitis for ankylosing spondylitis (AS) patients compared to clinical examinations. Twenty AS patients initiating etanerceptunderwent clinical and PDUS examinations of six bilateral entheseal sites at baseline and after 1, 2 and 3 months of treatment. Clinical and PDUS examinations identified at least one entheseal lesion in nine (45%) and 19 (95%) patients, respectively. Furthermore, of 240 entheseal sites examined in these 20 patients, PDUS detected 123 entheseal lesions (51.3% of sites), compared with only 47 entheseal lesions (19.6%) detected by clinical examination (P < 0.05). The entheseal lesions found on PDUS were most commonly identified by calcification (33.3%), tendon edema (29.2%), abnormal blood flow (25.8%), a thickened tendon (22.1%), cortical irregularity (12.9%), bony erosions (9.6%) and bursitis at the tendon insertion to the bone cortex (7.1%). Improvements in clinical symptoms and laboratory parameters, and significant decreases in PDUS scores were observed following treatment with etanercept. Improvements in PDUS scores continued during follow-up in patients who entered remission following treatment. In conclusion, PDUS improve detection of structural and inflammatory abnormalities of the enthesis in AS compared to physical examination. In addition, PDUS may be useful inascertaining medications.
This report details the CT and MR imaging findings of a primary orbital Ewing's sarcoma case involving the middle cranial fossa in a 13-year old boy. CT showed an ill-circumscribed homogeneous soft-tissue density mass with needle-like bone reaction. On MRI, the mass showed homogeneous iso-intensity on T1WI, heterogeneous hyperintensity on T2WI, and marked homogeneous enhancement. Meanwhile, the mass was hyper-intense on DWI, and ADC value was 575×10-6 mm2/s. The mass showed as high rCBV and rCBF, prolonged MTT based on DCSPWI, and wash-out pattern of TIC derived from the DCE-MRI. Our case suggests that functional MRI modalities, including DWI, DSC-PWI or DCE-MR, could provide additional information for differential diagnoses. Both CT and MRI should be performed and comprehensively analyzed for limiting differential diagnoses, determining lesion extension and facilitating operative approach.