Alcohol-associated capillarization of sinusoids: A critique since the discovery by Schaffner and Popper in 1963

This article reviews the literature on capillarization of hepatic sinusoids since its discovery in 1963. Liver sinusoidal endothelial cells are uniquely fenestrated and lack an underlying basement membrane. In chronic liver disease, the sinusoids capillarize and transform into systemic capillaries, a process termed capillarization of sinusoids. The histopathology is marked by defenestration, basement membrane formation, and space of Disse fibrogenesis. Capillarized sinusoids compromise the bidirectional exchange of materials between sinusoids and hepatocytes, leading to hepatocellular dysfunction. Sinusoidal capillarization was first described in active cirrhosis of alcoholics in 1963. Since then, it has been found in early and progressive stages of alcoholic hepatic fibrosis before the onset of cirrhosis. The sinusoidal structure is not altered in alcoholic steatosis without fibrosis. Defenestration impairs the ability of the endothelium to filter chylomicron remnants from sinusoids into the Disse's space, contributing to alcohol-induced postprandial hyperlipidemia and possibly atherosclerosis. Ethanol also modulates the fenestration dynamics in animals. In baboons, chronic alcohol consumption diminishes endothelial porosity in concomitance with hepatic fibrogenesis and in rats defenestrates the endothelium in the absence of fibrosis, and sometimes capillarizes the sinusoids. Acute ethanol ingestion enlarges fenestrations in rats and contracts fenestrations in rabbits. In sinusoidal endothelial cell culture, ethanol elicits fenestration dilation, which is likely related to its interaction with fenestration-associated cytoskeleton. Ethanol potentiates sinusoidal injury caused by cocaine, acetaminophen or lipopolysaccharide in mice and rats. Understanding ethanol's mechanisms on pathogenesis of sinusoidal capillarization and fenestration dynamics will lead to development of methods to prevent risks for atherosclerosis in alcoholism.     

An arduous journey from human pluripotent stem cells to functional pancreatic β cells

Type 1 and type 2 diabetes are caused by a destruction and decrease in the number of functional insulin‐producing β cells, respectively; therefore, the generation of functional β cells from human embryonic stem cells and human induced pluripotent stem cells, collectively known as human pluripotent stem cells (hPSCs), for potential cell replacement therapy and disease modelling is an intensely investigated area. Recent scientific breakthroughs enabled derivation of large quantities of human pancreatic β‐like cells in vitro, although with varied glucose‐stimulated insulin secretion kinetics. In the present review, we comprehensively summarize, compare and critically analyze the intricacies of these developing technologies, including differentiation platforms, robustness of protocols, and methodologies used to characterize hPSC‐derived β‐like cells. We also discuss experimental issues that need to be resolved before these β‐like cells can be used clinically.     

Partially-covered stent placement versus surgical gastrojejunostomy for the palliation of malignant gastroduodenal obstruction secondary to pancreatic cancer

Purpose

To compare the outcomes of partially covered self-expandable metallic stent (SEMS) placement with surgical gastrojejunostomy (GJ) in patients with gastroduodenal obstruction caused by pancreatic cancer.

Methods

The medical records of 107 patients with gastroduodenal obstruction caused by pancreatic cancer who underwent fluoroscopic partially covered SEMS placement (n = 75) or surgical GJ (n = 32) at our institution were reviewed.

Results

The technical (100% vs. 100%; P > 0.999) and clinical (98.7% vs. 96.9%; P = 0.511) success rates were similar between the SEMS and GJ group. The mean gastric outlet obstruction scoring system score was higher in the SEMS group at 1 week after treatment (2.3 ± 0.5 vs. 1.2 ± 0.4; P < 0.001) but was similar between the two groups at 1 month (2.7 ± 0.5 vs. 2.8 ± 0.5; P = 0.242). The median hospital stay was shorter in the SEMS group than in the GJ group (7 vs. 14 days; P < 0.001). The overall complication (22.7% vs. 28.1%; P = 0.547) and reintervention (21.3% vs. 25.0%; P = 0.677) rates were similar between the two groups. The median patency (99 vs. 138 days; P = 0.102) and survival (106 vs. 140 days; P = 0.245) were also similar between the two groups.

Conclusion

The outcomes of partially covered SEMS placement seem to be more favorable than surgical GJ in patients with gastroduodenal obstruction caused by pancreatic cancer.

     

Effects of exercise training on pathological cardiac hypertrophy related gene expression and apoptosis

This study determined whether exercise training prevents pathological hypertrophy in the left ventricle by modulation of myocardial and apoptosis-associated genes. We used spontaneously hypertensive rats (n=15, non-exercise SHR), exercise-trained SHR (n=15, treadmill exercise for 12 weeks), and sedentary Wistar-Kyoto (WKY) rats (n=15). Exercise-trained SHR expressed adaptive changes such as reduced body weight, heart rate, blood pressures, left ventricle wall thickness, lipid profiles, and homocysteine level. The mRNA expression of angiotensin converting enzyme, endothelin-1, and brain natriuretic peptides in the heart was lower in the exercise-trained SHR and in the WKY than in the non-exercise SHR, whereas mRNA expression of caveolin-3 and eNOS in the heart was higher. Bcl-2 protein was higher in the exercise-trained SHR than in the WKY and the non-exercise SHR. In contrast, Bax protein levels were lower in the exercise-trained SHR and in the WKY than in the non-exercise SHR. Furthermore, the levels of the active forms of caspase-3 (20 kDa) were lower in the exercise-trained SHR and in the WKY than in the non-exercise SHR. These findings suggest that exercise training prevents pathological hypertrophy in the left ventricle by modulation of myocardial genes and that it interferes with a signal transduction pathway of apoptosis secondary to the pathological cardiac hypertrophy.     

Identification of tumor suppressor loci on the long arm of chromosome 15 in primary small cell lung cancer

Small cell lung cancer (SCLC) frequently shows a loss of heterozygosity (LOH) on chromosome 15q. In order to define the commonly affected region on chromosome 15q, we tested 23 primary SCLCs by microsatellite analysis. By analyzing 43 polymorphic microsatellite markers located on chromosome 15q, we found that 14 (60.8%) of 23 tumors exhibited a LOH in at least one of the tested microsatellite markers. Two (14.3%) of the 14 tumors were found to have more than a 50% LOH on chromosome 15q. LOH was observed in five commonly deleted regions on 15q. Of those regions, LOH from D15S1012 to D15S1016 was the most frequent (47.8%). LOH was also observed in more than 20-30% of tumors at four other regions, from D15S1031 to D15S1007, from D15S643 to D15S980, from D15S979 to D15S202, and from D15S652 to D15S642. Four of the 23 tumors exhibited shifted bands in at least one of the tested microsatellite markers. Shifted bands occurred in 3.2% (29 of 914) of the loci tested. Our data suggests the presence of at least five tumor suppressor loci on chromosome 15q in SCLC, and further that these may play an important role in SCLC tumorigenesis.     

Effects of Coffee Intake on Incident Chronic Kidney Disease: A Community-Based Prospective Cohort Study

Background

Drinking coffee can raise public health problems, but the association between coffee and kidney disease is unknown. We studied whether coffee intake can affect the development of chronic kidney disease in the general population.

Diffuse Ependymal Dysembryoplastic Neuroepithelial Tumor Causing Spinal Drop Metastases: A Case Report

Dysembryoplastic neuroepithelial tumors (DNETs) arise mostly in the supratentorial cerebral cortex. A very rare case of intraventricular DNET with diffuse ependymal involvement, which causes spinal drop metastasis, is presented.     

Intravenous dexamethasone followed by oral prednisolone versus oral prednisolone in the treatment of childhood Henoch�CSch?nlein purpura

The aim of this study was to evaluate the effectiveness of intravenous corticosteroid therapy when Henoch–Sch?nlein purpura (HSP) patients are unable to tolerate oral medications due to abdominal pain. We retrospectively analyzed 111 children with a diagnosis of HSP (mean age 6.9 ± 2.3 years, male:female = 54:57) from the years 2000 to 2007. They were divided into two groups: 49 patients received only oral prednisolone (PL group) and 62 patients received oral prednisolone after intravenous dexamethasone (Dexa + PL group). Palpable purpura was seen in all 111 patients (100%), abdominal pain in 55 (50%), and arthralgia in 65 (59%). Dexa + PL group had significantly longer duration of fasting than PL group (0.7 ± 1.2 vs. 0.02 ± 0.1 days, P < 0.01) due to more severe and frequent abdominal pain (68 vs. 27%, P < 0.01). Intravenous dexamethasone resulted in the rapid resolution of abdominal pain or arthralgia in all patients without major complications. However, the development of nephritis (21% in PL group versus 32% in Dexa + PL group, P = 0.098), the number of relapse (4 vs. 11%, P = 0.167), and persistent nephritis at last follow-up (12 vs. 16%, P = 0.563) were not different between the two groups despite more severe symptoms in Dexa + PL group. Intravenous dexamethasone followed by oral prednisolone may be a useful and effective therapeutic strategy in HSP children who cannot tolerate oral medications due to severe abdominal pain.     

Clinical manifestation of cancer related stroke: retrospective case–control study

Cancer related stroke may have different phenotypes from non-cancer stroke, especially in terms of stroke progression and recurrence. We performed a case–control study to identify their incidences and risk factors in cancer related stroke. Between January 2001 and December 2009, we conducted a retrospective review of acute ischemic stroke patients with cancer who were admitted to Seoul National University Hospital, Seoul, Korea. The stroke patients without cancer served as control. We collected demographic variables, vascular risk factors, stroke phenotype, clinical course, and cancer information including diagnosis, stage, and treatment status. Among cancer stroke patients, the potential risk factor of stroke recurrence was evaluated. The mean age of the 102 cancer patients was 66.4 ± 10.8 years, and 64.7 % were men. The mean time interval from cancer diagnosis to stroke onset was 39.7 ± 60.9 months. The principal lesion pattern of cancer stroke was multiple dots extending single vascular territory (39.2 %), and they were associated with low hemoglobin and high fibrinogen levels. Stroke progression and recurrence were noted in 9.8 and 27.5 % of cancer stroke patients, and in 9.3 and 12.7 % of control patients, respectively. The stroke subtype was independently associated with recurrence of cancer stroke after multiple logistic regression (odds ratio = 3.165, 95 % confidence interval = 1.080–9.277, p = 0.036). Cancer related stroke has a distinct phenotype in terms of infarction pattern and laboratory findings. Stroke recurrence is frequently observed among cancer stroke patients, and its risk is related with stroke subtype.