Cancer-Associated Thrombosis in Cirrhotic Patients with Hepatocellular Carcinoma.

It is common knowledge that cancer patients are more prone to develop venous thromboembolic complications (VTE). It is therefore not surprising that patients with hepatocellular carcinoma (HCC) present with a significant risk of VTE, with the portal vein being the most frequent site (PVT). However, patients with HCC are peculiar as both cancer and liver cirrhosis are conditions that can perturb the hemostatic balance towards a prothrombotic state. Because HCC-related hypercoagulability is not clarified at all, the aim of the present review is to summarize the currently available knowledge on epidemiology and pathogenesis of non-malignant thrombotic complications in patients with liver cirrhosis and HCC. They are at increased risk to develop both PVT and non-splanchnic VTE, indicating that both local and systemic factors can foster the development of site-specific thrombosis. Recent studies have suggested multiple and often interrelated mechanisms through which HCC can tip the hemostatic balance of liver cirrhosis towards hypercoagulability. Described mechanisms include increased fibrinogen concentration/polymerization, thrombocytosis, and release of tissue factor-expressing extracellular vesicles. Currently, there are no specific guidelines on the use of thromboprophylaxis in this unique population. There is the urgent need of prospective studies assessing which patients have the highest prothrombotic profile and would therefore benefit from early thromboprophylaxis

New Perspectives in Liver Transplantation: From Regeneration to Bioengineering

Advanced liver diseases have very high morbidity and mortality due to associated complications, and liver transplantation represents the only current therapeutic option. However, due to worldwide donor shortages, new alternative approaches are mandatory for such patients. Regenerative medicine could be the more appropriate answer to this need. Advances in knowledge of physiology of liver regeneration, stem cells, and 3D scaffolds for tissue engineering have accelerated the race towards efficient therapies for liver failure. In this review, we propose an update on liver regeneration, cell-based regenerative medicine and bioengineering alternatives to liver transplantation

In-house validation of chromatographic speciation methods for arsenic in fishery products

The relatively high concentrations of arsenic found in shellfish in recent years have contributed to raise the threshold of attention of European Union, in terms of food security. Among the various factors that influence the toxicity of arsenic, the chemical form is of particular significance, given the high toxicity of the inorganic form in respect of the organic that frequently contaminates fishery products. The Expert Committee of FAO / WHO defined a provisional tolerable weekly intake (PTWI) of 15 mg/kg b.w. only for the inorganic form and, in view of definition of residual limits for arsenic in fish, it becomes necessary to have analytical methods able to differentiate inorganic form from the organic ones (e.g. monomethyland dimethylarsenic acid, arsenobetaine, arsenocholine). The purpose of this study was to optimize and validate an analytical method for the speciation of arsenic in fishery products, that could identify and quantify the organic forms of arsenic. Screening of organic forms of arsenic was carried out using HPLC (high performance liquid chromatography) coupled to a tandem mass spectrometry detector, while determination of total arsenic was carried out using the atomic absorption spectroscopy. The validation procedure was conducted according to the requirements of the European Community to allow the use of the present method by the Official Control laboratories. The matrices considered for method optimization and validation have been fish, molluscs and crustaceans from the coasts of southern Italy. Obtained results allowed the method to enter within the routinely activities of the laboratory and require method accreditation

EFFECTS OF NDL-PCB AND TCDD ON INTESTINAL EPITHELIAL CELLS HOMEOSTASIS

Polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins (PCDD) are persistent organic pollutants (POPs) recognized as causing adverse effects on humans, animals and environment. Exposure occurs mainly through the consumption of contaminated food, in particular those of animal origin. the aim of the current study was to evaluate the effects of three ndl-PCB congeners, PCB 138, PCB 153 and PCB 180, and tetrachlorodibenzo-p-dioxins (TCDD), alone and differently combined, on non tumorigenic rat intestinal epithelial cell line (IEC-6). The results of the current study showed that ndl-PCBs and TCDD reduced significantly cell viability only at the highest concentrations (50-100 µM and 0.1-1 µM, respectively); such effect was not linked to apoptosis induction or cell cycle arrest. The contemporary presence of more than one contaminant (differently combined) did not induce any enhancement of effects on IEC-6 cell line. Intestinal restitution was not affected by low non cytotoxic concentrations of ndl-PCBs and TCDD. The results of the current study highlight the need to continue the evaluation of toxic properties of ndl-PCBs, which represent a less studied PBCs; such studies could provide useful information in particular in term of risk assessment

Association between asymptomatic carotid atherosclerosis and degenerative aortic stenosis.

OBJECTIVE: Degenerative aortic stenosis shows similarities with atherosclerosis. To confirm the hypothesis that aortic stenosis is an "atherosclerosis-like" disease, we investigated the association between degenerative aortic stenosis and atherosclerosis of carotid arteries. METHODS: We studied 270 consecutive patients, 135 with degenerative aortic stenosis (trans-aortic peak velocity ≥ 2 m/sec) and other 135 subjects without aortic valve disease. All patients underwent echocardiography and ultrasound scan of the supra-aortic trunks to assess the presence of plaque and/or intima-media thickening (IMT). RESULTS: Atherosclerosis of carotid arteries (IMT and plaque) was significantly more frequent in patients with aortic stenosis than in controls (95.5% vs. 66.6%, p < 0.0001). The same result was confirmed as concerns carotid plaques (69.6% vs. 42.2%, p < 0.0001). In addition, there was a significant association between aortic stenosis and degenerative carotid plaque (OR = 3.13; 95% C.I. = 1.90-5.17). Thus the presence of a linear correlation between the trans-aortic peak velocity of the cases and the thickness of the plaques and IMT was evaluated by calculating the coefficient of correlation (R = 0.15 for plaque and R = 0.53 for IMT). CONCLUSIONS: The presence of carotid atherosclerosis is associated with degenerative aortic stenosis and the severity of aortic stenosis corresponds to an increase of the thickness of plaque and IMT. This relationship is quite new. Our result strengthens the pathogenetic hypothesis "atherosclerosis-like" of degenerative aortic stenosis and suggest the ultrasound scan as a non invasive method for risk stratification in patient with aortic stenosis, with therapeutic implications especially for higher risk subgroups

Heavy Metal Levels in Dog Liver and Kidney in Naples (Campania, Italy)

The aim of the current study was to carry out a retrospective analysis of heavy metal (Pb, Cd, and Hg) levels in liver and kidney of 38 dogs living in an urban habitat (city of Naples). Tissues were homogenized, digested in a microwave digestion system, and analyzed by atomic absorption spectrometry. The results of this study showed generally low levels of heavy metals in tissues of all examined dogs; only mercury concentrations in kidneys of pet dogs were higher than in stray dogs, and no significant age-dependent differences in metal levels were shown between the two groups. In conclusion, these results suggest the involvement of ad hoc-formulated pet food exposure to heavy metals in domestic animals

Levels of heavy metals in liver and kidney of dogs from urban environment

Lead, cadmium and mercury were detected in liver and kidney tissue of dogs from an urban habitat. Samples were digested in a microwave system and analyzed by atomic absorption spectroscopy. Results of the current study showed that at least one of the three heavy metals was detected in tissues of all examined dogs. These findings make us suppose that humans are exposed to the same heavy metals similar to those of dogs that are exposed since they share the same environment. Mercury concentrations detected in kidney of household dogs were higher than stray dogs, therefore the involvement of pet food in exposure to mercury can be supposed

CTCF and BORIS Regulate Rb2/p130 Gene Transcription: A Novel Mechanism and a New Paradigm for Understanding the Biology of Lung Cancer

Although innumerable investigations regarding the biology of lung cancer have been carried out, many aspects thereof remain to be addressed, including the role played by the retinoblastoma-related protein Rb2/ p130 during the evolution of this disease. Here we report novel findings on the mechanisms that control Rb2/ p130 gene expression in lung fibroblasts and characterize the effects of Rb2/p130 deregulation on the proliferative features of lung cancer cells.We revealed for the first time that in lung fibroblasts the expression of Rb2/p130 gene is directly controlled by the chromatin insulator CCCTC-binding factor, CTCF, which by binding to the Rb2/p130 gene promoter induces, and/or maintains, a specific local chromatin organization that in turn governs the transcriptional activity of Rb2/p130 gene. However, in lung cancer cells the activity of CTCF in controlling Rb2/p130 gene expression is impaired by BORIS, a CTCF-paralogue, which by binding to the Rb2/p130 gene could trigger changes in the chromatin asset established by CTCF, thereby affecting CTCF regulatory activity on Rb2/p130 transcription. These studies not only provide essential basic insights into the molecular mechanisms that control Rb2/p130 gene expression in lung cancer, but also offer a potential paradigm for the actions of other activators and/or corepressors, such as CTCF and BORIS, that could be crucial in explaining how alterations in the mechanism regulating Rb2/p130 gene expression may accelerate the progression of lung tumors, or favor the onset of recurrence after cancer treatment. Mol Cancer Res; 9(2); 225–33. 2011 AACR

LEVELS OF HEAVY METALS IN ITALIAN MARKETED CANNED TUNA

Fish products are essential and irreplaceable components of human diet; nevertheless, they could result in a risk to the health of consumers due to the potential content of some xenobiotics such as heavy metals and persistent organic contaminants (Debeka et al., 2004; Storelli et al., 2005). Constant control network and surveys are valuable tools in order to prevent such risk and to ensure product quality and consumers??? safety. The aim of the current study was to measure the levels of some heavy metals (Hg, Pb, Cd) in samples of marked canned tuna in olive oil. The results showed that levels of Cd and Hg were always within the law limits and, in many samples, below the detection limit. Pb was found in concentrations exceeding the law limits in 9.8% of the analyzed samples. In conclusion, the results of the current study, quite reassuring in terms of food safety, highlighted the need to constantly monitor the levels of some chemical contaminants in fish products such as heavy metals that might endanger the health of the consumers