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  • In previous works Gotor Vila et al c

    2020-09-15

    In previous works (Gotor-Vila et al., 2017c), differences in solubility between the two carriers used during formulation were evidenced. Summarizing, maltodextrin (BA3 product) resulted in a much more soluble product since this polysaccharide is typically composed of an amount of reducing sugars between 3 and 20% (whereas starch is close to zero) (Shamekh et al., 2002). In this study, it was also observed that BA3 samples stored at 4 °C (in either flasks or bags) the moisture content, and therefore aw, increased much more compared to the BA4 product stored at 4 °C. Therefore, we also aimed to prove the degree of dispersion in water of different packaged formulations including both carriers. As it was observed, products including potato starch (BA4) were not so easy to dissolve showing a retention time prior precipitation considerably shorter compared to the BA3 product (rate of precipitation > 31.1 and >2.0 %, respectively). It was measured in terms of turbidity, a qualitative characteristic which is impacted by solids obstructing the transmittance of light through a water sample. As it was demonstrated, products including maltodextrin would have a long-rate spray; however, potato starch enables a better deposition and maintenance of the product in the surface of gpcr signaling (Gotor-Vila et al., 2017c).
    Introduction Fibrosis progression is the common consequence of most chronic liver diseases and histologic examination of a liver biopsy specimen is the reference standard for the assessment of liver fibrosis. However, liver biopsy is burdened by invasiveness and low degree of acceptance by patients, potentially lethal complications, sampling error, observer-dependent diagnostic variability and handling costs [1]. In the last decade, non-invasive and reproducible methodologies, with an acceptable level of diagnostic accuracy have been proposed for the non-invasive assessment of fibrosis [2], [3]. These mainly include the measurement of tissue elasticity by transient elastography and serum markers of liver fibrosis [4], [5]. The gpcr signaling “indirect serum markers” are panels of clinical and biochemical parameters not directly related to extracellular matrix metabolism while the “direct serum markers”, such as the serum levels of molecules diffused into the systemic circulation, are related to the metabolism of the extracellular matrix [6]. Currently, the ELF score is derived by the assessment of direct serum markers of fibrosis, namely hyaluronic acid, aminoterminal propeptide of type III collagen and tissue inhibitor of matrix metalloproteinase 1 [7]. All non-invasive fibrosis tests to date were developed and calibrated with reference to semi-quantitative histological scoring systems, such as Ishak’s or METAVIR, rather than quantitative histological measurement of fibrosis, which would be more accurate and appropriate. Indeed, existing scoring systems do not represent a measurement of quantitative fibrosis, but rather a categorical description of both architecture and fibrosis. Collagen proportionate area (CPA) is a validated method for the quantification of fibrosis by measuring hepatic collagen using digital image analysis [8], [9], [10], [11], [12], [13]. This method was first described by Calvaruso et al. [8], who determined relationships between computer–assisted digital analysis, Ishak score and HVPG. The authors found a significant relationship between CPA and HVPG, indicating that computer-assisted digital image analysis measurement of CPA has clinical relevance, because it could be useful to stratify prognostic groups. Based on these premises, the aims of this study was to evaluate the diagnostic accuracy of CPA for the diagnosis of fibrosis stages using a standard semi-quantitative method (Ishak’s score) and to provide a further validation of ELF by comparing ELF with a method (CPA) able to assess liver fibrosis quantitatively.
    Study design and methods The study was performed on 143 liver biopsy samples of available tissue blocks largely from patients with HCV-related chronic liver disease, obtained at the time of the original ELF study at the University of Florence University Hospitals (AOUC) in Florence, Italy, as a part of an international, multicenter, cross-sectional cohort study [7].