Anti-Melanogenic Property of Geoditin A in Murine B16 Melanoma Cells

Geoditin A, an isomalabaricane triterpene isolated from marine sponge Geodia japonica, has been demonstrated to induce apoptosis in leukemia HL60 cells and human colon HT29 cancer cells through an oxidative stress, a process also interfering with normal melanogenesis in pigment cells. Treatment of murine melanoma B16 cells with geoditin A decreased expression of melanogenic proteins and cell melanogenesis which was aggravated with adenylate cyclase inhibitor SQ22536, indicating melanogenic inhibition was mediated through a cAMP-dependent signaling pathway. Immunofluorescence microscopy and glycosylation studies revealed abnormal glycosylation patterns of melanogenic proteins (tyrosinase and tyrosinase-related protein 1), and a co-localization of tyrosinase with calnexin (CNX) and lysosome-associated membrane protein 1 (LAMP-1), implicating a post-translational modification in the ER and a degradation of tyrosinase in the lysosome. Taken together, potent anti-melanogenic property and the relatively low cytotoxicity of geoditin A have demonstrated its therapeutic potential as a skin lightening agent

The assessment of motor carrier lane profitability : methods and implementation

The traffic moved between two cities by a long-haul carrier is commonly termed a lane. The purpose of this study is to demonstrate methods to assess the profitability of individual lanes. To tackle the problem of lane profitability, one needs to have accurate and valid data of revenue and costs. In view of the importance of properly prepared data, a secondary purpose of this study is to recommend accounting procedures to record data in a usable form for further studies of this kind. The concept of revenue for a lane is not difficult to understand. However, the concept of cost for a lane raises some difficult questions. Since a terminal handles traffic from a variety of lanes, the crux of the problem is to disaggregate the terminal costs to each individual lane. Statistical costing is the main tool used in this study. It is not the most accurate method but is less costly than most other methods. Thus, it is often an indeal substitution for detailed engineering studies. Statistical methods have applicability when direct observation of the relationship between cost and output is difficult or impossible. To this end, regression analysis was proposed extensively in the study to examine the behaviour of different cost elements. With a good grasp of the relationship between terminal costs and terminal output (activities) one can apportion the related terminal costs to the lanes of interest. This study presents a normative model. To construct the model, the examination of a common motor carrier's operation has provided much insight regarding (1) the kinds of data that are generally available, (2) how the available data can be improved, and (3) how the constructed model relates to the motor carrier examined. To appreciate the subtleties inherent in this study, a general understanding of the industry as well as the daily operation of a motor carrier is required. To assess the profitability relating to different lanes, one requires some workable methods, and above all, workable data.Business, Sauder School ofGraduat

Outcome and risk factor analysis of patients who underwent open infrarenal aortic aneurysm repair

Introduction: The aim of this study was to evaluate the short- and long-term outcomes in patients who underwent open infrarenal aortic aneurysm repair. Methods: Consecutive patients who underwent open repair of infrarenal aortic aneurysms at our institution from July 1st 1990 to June 30th 2012 were reviewed from a prospective collected departmental database. Short-term outcomes included 30-day mortality and peri-operative complications. Independent risk factors to predict 30-day mortality were identified. Long-term survival and secondary interventions were also reported. Results: Three hundred and eighty-three patients (317 males, median age 72 years with a range of 15–90 years) underwent open infrarenal aortic aneurysm repair during the period, of whom 266 (69.5%) were elective, 18 (4.7%) were urgent for symptomatic but nonruptured cases, and 99 (25.8%) were emergency procedures for ruptured aneurysms. Mean aneurysm size was 6.5 cm (ranging from 2.5 cm to15 cm). All patients were followed up for at least 24 months with a mean follow up period 163 months. Overall 30-day mortality was 11.0% (36.4% for ruptured cases, 11.1% for symptomatic cases, and 1.5% for elective cases; p < 0.001). Preexisting renal disease and ruptured aneurysms were independent risk factors for 30-day mortality (p = 0.001 and p = 0.006 respectively). Systemic complications included 50 cardiac events, 52 respiratory events, six renal events, three cerebral vascular accidents, and one deep vein thrombosis/pulmonary embolism. Local complications included two anastomotic/graft hemorrhage, 10 distal thrombosis/embolisms, five bowel ischemias, one spinal cord ischemia, and 17 wound complications. The ruptured group presented survival rates of 53.5%, 50.5%, 47.5%, 42.3%, 38.0%, 21.9%, and 12.5% at 1 year, 2 years, 3 years, 4 years, 5 years, 10 years, and 15 years, respectively; while nonruptured survival rates were 91.5%, 88.0%, 83.7%, 78.3%, 73.0%, 43.0%, and 25.3%, respectively (log rank p < 0.001). For those who died 30 days after the operation, only six patients (1.8%) died from aneurysm related mortality. A total of three (0.9%) patients underwent late re-interventions, one for late aorto-enteric fistulae and two for anastomotic pseudoaneurysms. Conclusion: In the current era of endovascular repair, open infrarenal aneurysm repair is effective and durable, and has very low secondary interventions rates

Geoditin A Induces Oxidative Stress and Apoptosis on Human Colon HT29 Cells

Geoditin A, an isomalabaricane triterpene isolated from the marine sponge Geodia japonica, has been demonstrated to dissipate mitochondrial membrane potential, activate caspase 3, decrease cytoplasmic proliferating cell nuclear antigen (PCNA), and induce apoptosis of leukemia cells, but the underlying mechanism remains unclear [1]. In this study, we found fragmentation of Golgi structure, suppression of transferrin receptor expression, production of oxidants, and DNA fragmentation in human colon cancer HT29 cells after treatment with geoditin A for 24 h. This apoptosis was not abrogated by chelation of intracellular iron with salicylaldehyde isonicotinoyl hydrazone (SIH), but suppressed by N-acetylcysteine (NAC), a thiol antioxidant and GSH precursor, indicating that the cytotoxic effect of geoditin A is likely mediated by a NAC-inhibitable oxidative stress. Our results provide a better understanding of the apoptotic properties and chemotherapeutical potential of this marine triterpene