Bone metastases as initial presentation of hepatocellular carcinoma

Extra-hepatic spread is present in 5% to 15% of patients with hepatocellular carcinoma(HCC) at the time of diagnosis. The most frequent sites are lung and regional lymph nodes. Here, we report 3 cases of unsuspected HCC with symptoms due to bone lesions as initial presentation. Morphological characteristics and immunohistochemistry from the examined bone were the key data for diagnosis. None of the patients had an already known chronic liver disease. Differential diagnoses with HCC upon ectopic liver disease or hepatoid adenocarcinoma were shown. Therapy with the orally active multikinase inhibitor sorafenib plus symptomatic treatment was indicated.

Cardiac ischemic preconditioning prevents dystrophin proteolysis by MMP-2 inhibition

Dystrophin is a membrane-associated protein responsible for structural stability of the sarcolem-ma in cardiac myocytes and is very sensitive to ischemic damage.The goal of our study was to determine if ischemic preconditioning could prevent dystrophin breakdown through inhibition of matrix metalloprotein-ase-2(MMP-2)activity.Isolated rabbit hearts were subjected to global ischemia with or without reperfusion in order to evaluate if dystrophin is preserved by ischemic preconditioning through MMP-2 inhibition.Ischemic preconditioning significantly reduced the infarct size induced by 30 min of ischemia and 180 min of reperfusion.Importantly,it also diminished dystrophin proteolysis and attenuated MMP-2 activity after 30 min ischemia.Thus,our study shows a novel protective role of ischemic preconditioning as a mechanism of preservation of plasma membrane integrity by inhibiting MMP-2 activation.

Astrocytes and retrograde degeneration of nigrostriatal dopaminergic neurons in Parkinson’s disease:removing axonal debris

Objective:The dopaminergic nigrostriatal neurons(DA cells)in healthy people present a slow degeneration with aging,which produces cellular debris throughout life.About 2%-5%of people present rapid cell degeneration of more than 50%of DA cells,which produces Parkinson's disease(PD).Neuroinflammation accelerates the cell degeneration and may be critical for the transition between the slow physiological and the rapid pathological degeneration of DA cells,particularly when it activates microglial cells of the medial forebrain bundle near dopaminergic axons.As synaptic debris produced by DA cell degeneration may trigger the parkinsonian neuroinflammation,this study investigated the removal of axonal debris produced by retrograde degeneration of DA cells,paying particular attention to the relative roles of astrocytes and microglia.Methods:Rats and mice were injected in the lateral ventricles with 6-hydroxydopamine,inducing a degeneration of dopaminergic synapses in the striatum which was not accompanied by non-selective tissue damage,microgliosis or neuroinflammation.The possible retrograde degeneration of dopaminergic axons,and the production and metabolization of DA-cell debris were studied with immunohistochemical methods and analyzed in confocal and electron microscopy images.Results:The selective degeneration of dopaminergic synapses in the striatum was followed by a retrograde degeneration of dopaminergic axons whose debris was found within spheroids of the medial forebrain bundle.These spheroids retained mitochondria and most(e.g.,tyrosine hydroxylase,the dopamine transporter protein,and amyloid precursor protein)but not all(e.g.,α-synuclein)proteins of the degenerating dopaminergic axons.Spheroids showed initial(autophagosomes)but not late(lysosomes)components of autophagy(incomplete autophagy).These spheroids were penetrated by astrocytic processes of the medial forebrain bundle,which provided the lysosomes needed to continue the degradation of dopaminergic debris.Finally,dopaminergic proteins were observed in the cell somata of astrocytes.No microgliosis or microglial phagocytosis of debris was observed in the medial forebrain bundle during the retrograde degeneration of dopaminergic axons.Conclusions:The present data suggest a physiological role of astrocytic phagocytosis of axonal debris for the medial forebrain bundle astrocytes,which may prevent the activation of microglia and the spread of retrograde axonal degeneration in PD.

Treatment, residual chlorine and season as factors affecting variability of trihalomethanes in small drinking water systems

Seasonal variability in source water can lead to challenges for drinking water providers related to operational optimization and process control in treatment facilities. The objective of this study is to investigate seasonal variability of water quality in municipal small water systems （〈 3000 residents） supplied by surface waters. Residual chlorine and trihalomethanes （THM） were measured over seven years （2003-2009）. Comparisons are made within each system over time, as well as between systems according to the type of their treatment technologies. THM concentrations are generally higher in the summer and autumn. The seasonal variability was generally more pronounced in systems using chlorination plus additional treatment. Chloroform, total THM （TTHM） and residual chlorine concentrations were generally lower in systems using chlorination plus additional treatment. Conversely, brominated THM concentrations were higher in systems using additional treatment. Residual chlorine was highest in the winter and lowest in the spring and summer. Seasonal variations were most pronounced for residual chlorine in systems with additional treatment. There was generally poor correlation between THM concentrations and concentrations of residual chlorine. Further study with these data will be beneficial in finding determinants and indicators for both quantity and variability of disinfection byproducts and other water quality parameters.

Concentrations of disinfection by-products in swimming pool following modifications of the water treatment process:An exploratory study

The formation and concentration of disinfection by-products（DBPs） in pool water and the ambient air vary according to the type of water treatment process used. This exploratory study was aimed at investigating the short-term impact of modifications of the water treatment process on traditional DBP levels（e.g., trihalomethanes（THMs）, chloramines） and emerging DBPs（e.g., Halonitromethanes, Haloketones, NDMA） in swimming pool water and/or air. A sampling program was carried to understand the impact of the following changes made successively to the standard water treatment process： activation of ultraviolet（UV）photoreactor, halt of air stripping with continuation of air extraction from the buffer tank,halt of air stripping and suppression of air extraction from the buffer tank, suppression of the polyaluminium silicate sulfate（PASS） coagulant. UV caused a high increase of Halonitromethanes（8.4 fold）, Haloketones（2.1 fold）, and THMs in the water（1.7 fold） and, of THMs in the air（1.6 fold） and contributed to reducing the level of chloramines in the air（1.6fold） and NDMA in the water（2.1 fold）. The results highlight the positive impact of air stripping in reducing volatile contaminants. The PASS did not change the presence of DBPs, except for the THMs, which decrease slightly with the use of this coagulant. This study shows that modifications affecting the water treatment process can rapidly produce important and variable impacts on DBP levels in water and air and suggests that implementation of any water treatment process to reduce DBP levels should take into account the specific context of each swimming pool.