Non invasive tools for the diagnosis of liver cirrhosis

Liver cirrhosis (LC), the end stage of many forms of chronic hepatitis of different etiologies is a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules surrounded by annular fibrosis. This chronic progressive clinical condition, leads to liver cell failure and portal hypertension, which can favour the onset of hepatocellular carcinoma. Defining the phase of the natural history is crucial for therapeutic choice and prognosis. Liver biopsy is currently considered the best available standard of reference but it has some limits, so alternative tools have been developed to substitute liver biopsy when assessing liver fibrosis. Serum markers offer a cost-effective alternative to liver biopsy being less invasive and theoretically without complications. They can be classified into direct and indirect markers which may be used alone or in combination to produce composite scores. Diagnostic imaging includes a number of instruments and techniques to estimate liver fibrosis and cirrhosis like ultrasound (US), US Doppler, contrast enhanced US and Elastography. US could be used for the diagnosis of advanced LC while is not able to evaluate progression of fibrosis, in this case Elastography is more reliable. This review aims to revise the most recent data from the literature about non invasive methods useful in defining liver fibrosis

Detection of vitellogenin in a subpopulation of sea urchin coelomocytes

Sea urchin vitellogenin is a high molecular weight glycoprotein, which is the precursor of the major yolk protein present in the unfertilized egg. Vitellogenin processing into the major yolk protein and its further enzymatic cleavage during sea urchin embryonic development, has been extensively described, and the adhesive properties of the processed molecule have been studied. The function of vitellogenin in the adult, where it has been found in the coelomic fluid of both male and female individuals, is still unknown, although its role on promoting the adhesion of embryonic cells has been shown. In this report we describe the detection of vitellogenin in lysates of whole circulating coelomocytes of both male and female sea urchins of the species Paracentrotus lividus. By metrizoic acid gradients we purified total coelomocytes into six subpopulations that were tested for the occurrence of the molecule using vitellogenin-specific polyclonal antibodies. We detected vitellogenin only in the coelomocyte subpopulation called colorless spherule cells, packed in kidney-shaped granules located around the nucleus. We also showed that coelomocytes respond to stress conditions by discharging vitellogenin into the medium. This result together with previous observations on the adhesive properties of the molecule suggest a role for vitellogenin in the clotting phenomenon occurring after host invasion

Novel Combination of Sorafenib and Celecoxib Provides Synergistic Anti-Proliferative and Pro-Apoptotic Effects in Human Liver Cancer Cells

Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, recently received FDA approval for the treatment of advanced HCC. However, although sorafenib is well tolerated, concern for its safety has been expressed. Celecoxib (Celebrex®) is a selective cyclooxygenase-2 (COX-2) inhibitor which exhibits antitumor effects in human HCC cells. The present study examined the interaction between celecoxib and sorafenib in two human liver tumor cell lines HepG2 and Huh7. Our data showed that each inhibitor alone reduced cell growth and the combination of celecoxib with sorafenib synergistically inhibited cell growth and increased apoptosis. To better understand the molecular mechanisms underlying the synergistic antitumor activity of the combination, we investigated the expression profile of the combination-treated liver cancer cell lines using microarray analysis. Combination treatment significantly altered expression levels of 1,986 and 2,483 transcripts in HepG2 and Huh7 cells, respectively. Genes functionally involved in cell death, signal transduction and regulation of transcription were predominantly up-regulated, while genes implicated in metabolism, cell-cycle control and DNA replication and repair were mainly down-regulated upon treatment. However, combination-treated HCC cell lines displayed specificity in the expression and activity of crucial factors involved in hepatocarcinogenesis. The altered expression of some of these genes was confirmed by semi-quantitative and quantitative RT-PCR and by Western blotting. Many novel genes emerged from our transcriptomic analyses, and further functional analyses may determine whether these genes can serve as potential molecular targets for more effective anti-HCC strategies

Experiments on crack propagation and threshold at defects in press-fits of railway axles

Fatigue strength under fretting fatigue is one of the open problems in the area of fatigue. In the case of railway wheel-axle press-fits, there are no records of recent failures because design rules are today based on making the shape of geometrical transitions the most stressed point. However, it is important to analyze correctly the acceptability of defects and micro-cracks at press-fits. In this paper, after a preliminary presentation of the results obtained by a new criterion for predicting the non-propagation of cracks under rolling contact fatigue conditions, a new series of experiments on full-scale axle press-fits containing artificial defects is presented and discussed. Results show the modified Dang Van criterion is adequate for describing the development of natural cracks and cracks from artificial defects. The latter, characterized by a depth of 250 350 m, are competitors of fretting cracks naturally developed from surface scars and surface damage

Hidatidosis ósea: nuestra casuística

Se revisan los resultados de 16 casos de hidatidosis musculoesquelética tratados en la Unidad de Sépticos del Aparato Locomotor del Hospital Universitario "La Fe" de Valencia en el período 1972-1989. Las dificultades diagnósticas fueron importantes, siendo en 5 de los casos un diagnóstico operatorio. Analizados los métodos de tratamiento se llega a la conclusión de que la curación definitiva sólo se consigue con la resección completa y amplia de la lesión. Los curetajes, acompañados o no de aseptizaciones químicas, suelen dar recidivas. Se recomienda combinar el tratamiento médico con el quirúrgico.The results of 16 cases of musculoskeletal hydatidosis treated in the locomotive Apparatus Septic Unit of the Valencia University Hospital "La Fe" between 1972 and 1989 wer e reviewed. The diagnostic difficulties wer e marked and 5 cases wer e diagnosed at surgery. After analyzing the therapeutical approaches, it is drawn the conclusion that a definitive healing is achieved only when an extensive and complete resection is done. Curettage, with and without chemical aseptization, generally results in recurrence. A combined medical and surgical treatment is recommended

Heat shock protein 70 serum levels differ significantly in patients with chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma.

Members of the heat shock protein 70 (HSP70) family play an important role in assisting protein folding, preventing protein aggregation and transport of proteins across membranes under physiological conditions. Following environmental (i.e., irradiation, chemotherapy), physiological (i.e., cell growth, differentiation), and pathophysiological (i.e., inflammation, tumorigenesis) stress, the synthesis of heat shock proteins (HSPs) is highly up-regulated, whereas protein synthesis in general is reduced. In contrast to normal cells, many tumor entities including hepatocellular carcinoma (HCC) overexpress HSP70, the major-stress-inducible member of the HSP70 family, present it on their cell surface and secrete it into the extracellular milieu. Herein, the prognostic relevance of serum HSP70 levels in patients with chronic hepatitis (CH; n = 50), liver cirrhosis (LC; n = 46), and HCC (n = 47) was analyzed. Similar to other tumor entities, HSP70 is also present on the surface of primary HCC cells. The staining intensity of intracellular HSP70 in HCC tissue is stronger compared to control and cirrhotic liver sections. HSP70 serum levels in all HCC patients were significantly higher compared to a control group without liver disease (n = 40). No significant age- and gender-related differences in HSP70 serum levels were observed in male and female healthy human volunteers (n = 86). Patients with CH (n = 50) revealed significantly higher HSP70 serum levels compared to the control group, however, these values were significantly lower than those of HCC patients (n = 47). Furthermore, a subgroup of patients with LC who subsequently developed HCC (LC-HCC, n = 13) revealed higher HSP70 serum levels than patients with LC (n = 46, p = 0.05). These data indicate that serum HSP70 levels are consecutively increased in patients with CH, LC and liver carcinomas and thus might have a prognostic value

Nanostructured Lipid Carriers-Containing Anticancer Compounds: Preparation, Characterization, and Cytotoxicity Studies

This article describes the development of nanostructured lipid carriers (NLC) as colloidal carriers for two antitumor compounds that possess a remarkable antineoplastic activity. But their limited stability and low solubility in water could give a very low parenteral bioavailability. Results revealed an enhancement of the cytotoxicity effect of drug-loaded NLC on human prostate cancer (PC-3) and human hepatocellular carcinoma (HuH-6, HuH-7) cell lines with respect to that of both free drugs. Results of characterization studies strongly support the potential application of these drugs-loaded NLC as prolonged delivery systems for lipophilic drugs by several administration routes, in particular for intravenous administration

Potential uses of olive oil secoiridoids for the prevention and treatment of cancer: A narrative review of preclinical studies

The Mediterranean diet (MD) is a combination of foods mainly rich in antioxidants and anti-inflammatory nutrients that have been shown to have many health-enhancing effects. Extra-virgin olive oil (EVOO) is an important component of the MD. The importance of EVOO can be attributed to phenolic compounds, represented by phenolic alcohols, hydroxytyrosol, and tyrosol, and to secoiridoids, which include oleocanthal, oleacein, oleuropein, and ligstroside (along with the aglycone and glycosidic derivatives of the latter two). Each secoiridoid has been studied and char-acterized, and their effects on human health have been documented by several studies. Secoiridoids have antioxidant, anti-inflammatory, and anti-proliferative properties and, therefore, exhibit anti-cancer activity. This review summarizes the most recent findings regarding the pharmacological properties, molecular targets, and action mechanisms of secoiridoids, focusing attention on their preventive and anti-cancer activities. It provides a critical analysis of preclinical, in vitro and in vivo, studies of these natural bioactive compounds used as agents against various human cancers. The prospects for their possible use in human cancer prevention and treatment is also discussed

Synthetic peptide-labelled micelles for active targeting of cells overexpressing EGF receptors

The goal of nanomedicine is to transport drugs to pathological tissues, reducing side effects while increasing targeting and efficacy. Aggregates grafted by bioactive molecules act as the active targeting agents. Among bioactive molecules, peptides, which are able to recognize overexpressed receptors on cancer cell membranes, appear to be very promising. The aim of this study was to formulate analog peptide-labeled micelles enabled to potentially deliver highly hydrophobic drugs to cancer cells overexpressing epidermal growth factor (EGF) receptor (EGFR). The selected synthetic peptide sequences were anchored to a hydrophobic moiety, aiming to obtain amphiphilic peptide molecules. Mixed micelles were formulated with Pluronic® F127. These micelles were fully characterized by physico-chemical methods, estimating the critical micellar concentration (CMC) by fluorescence. Their sizes were established by dynamic light scattering (DLS) analysis. Then, micelles were also tested in vitro for their binding capacity to human hepatocellular carcinoma (HCC) cell lines overexpressing EGF