211 research outputs found

    The time has come to look for metabolic dysfunction-associated fatty liver disease in adult patients with type 1 Gaucher disease

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    MAFLD is highly prevalent in Gaucher type 1 adult patients as well as in the general population and may worsen liver disease progression. Hepatic complications should be followed up. A healthy lifestyle and therapies of cardiometabolic risk factors should be recommended in Gaucher disease patients

    NAFLD in Some Common Endocrine Diseases: Prevalence, Pathophysiology, and Principles of Diagnosis and Management

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    Secondary nonalcoholic fatty liver disease (NAFLD) defines those complex pathophysiological and clinical consequences that ensue when the liver becomes an ectopic site of lipid storage owing to reasons other than its mutual association with the metabolic syndrome. Disorders affecting gonadal hormones, thyroid hormones, or growth hormones (GH) may cause secondary forms of NAFLD, which exhibit specific pathophysiologic features and, in theory, the possibility to receive an effective treatment. Here, we critically discuss epidemiological and pathophysiological features, as well as principles of diagnosis and management of some common endocrine diseases, such as polycystic ovary syndrome (PCOS), hypothyroidism, hypogonadism, and GH deficiency. Collectively, these forms of NAFLD secondary to specific endocrine derangements may be envisaged as a naturally occurring disease model of NAFLD in humans. Improved understanding of such endocrine secondary forms of NAFLD promises to disclose novel clinical associations and innovative therapeutic approaches, which may potentially be applied also to selected cases of primary NAFLD

    Note sul rivestimento parietale di due nicchie poste lungo il muro perimetrale della strada basolata alle spalle della Basilica di Massenzio

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    On the wall with niches that characterizes the paved road behind the Basilica of Maxentius (so-called intercapedine) there is a wall covering made with painted plaster and concretions. The limited remains, concentrated in the sector in which the road bends at right angles, allow you to reconstruct a geometric decorative pattern with colored bands inside two niches with a tympanum pattern. Unusual and particularly interesting is the technique adopted for the realization that sees the insertion of pumice stones soaked in the same color used for the laying of the bottom, a solution that currently finds sporadic examples mostly attributable to environments that simulate caves (well known as “finta grotta”)

    Do Nonalcoholic Fatty Liver Disease and Fetuin-A Play Different Roles in Symptomatic Coronary Artery Disease and Peripheral Arterial Disease?

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    Nonalcoholic fatty liver disease (NAFLD) is strongly associated with both atherosclerotic cardiovascular disease (CVD) and Fetuin-A. However, the association of Fetuin-A with atherosclerosis is more controversial. We hypothesized that the pathogenic interplay of NAFLD, Fetuin-A and atherosclerosis varies based on arterial site. Accordingly, we aimed to assess NAFLD prevalence, Fetuin-A values and their relationship with symptomatic atherosclerosis occurring in different localizations: coronary artery disease (CAD) vs. peripheral arterial disease (PAD)

    Successful Treatment of Enterocutaneous Fistula in a Hemodialysis Patient with Somatostatin

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    Although cysticercosis is the most common parasitic disease affecting the central nervous system, spinal cysticercosis is rare. A rare form of spinal cysticercosis involving the whole spinal canal is presented. A 45-year-old Korean male had a history of intracranial cysticercosis and showed progressive paraparesis. Spinal magnetic resonance scan showed multiple cysts compressing the spinal cord from C1 to L1. Three different levels (C1-2, T1-3, and T11-L1) required operation. Histopathological examination confirmed cysticercosis. The patient improved markedly after surgery

    Liver steatosis is highly prevalent and is associated with metabolic risk factors and liver fibrosis in adult patients with type 1 Gaucher disease

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    Background and Aims: Gaucher disease (GD) is associated with peculiar metabolic abnormalities (ie hypermetabolic state, peripheral insulin resistance, dyslipidaemia), partially reverted by enzyme replacement therapy (ERT) at the expense of weight gain. Such metabolic alterations together with an unhealthy lifestyle acquired by an ageing GD population may favour the development of liver steatosis. We aimed at evaluating the prevalence of significant liver steatosis and at identifying the factors associated with liver steatosis in a cohort of patients with type 1 GD. Methods: Twenty adult type 1 GD patients from an Italian academic referral centre were prospectively submitted to vibration-controlled transient elastography (Fibroscan®) with controlled attenuation parameter (CAP); significant steatosis was defined as CAP values ≥250 dB/min. Results: Median CAP values were 234 [165-358] dB/min and 8 patients (40%) had significant steatosis. Significant steatosis was associated with indices of adiposity (weight, BMI and waist circumference), high blood pressure, insulin resistance and metabolic syndrome. GD-related variables and dose and duration of ERT were not associated with significant steatosis. In the subgroup of 16 patients on stable ERT for at least 24 months, CAP resulted significantly and positively associated with liver stiffness (rho 0.559, P =.024). Conclusions: Significant steatosis is highly prevalent in adult type 1 GD patients and is strongly associated with a worse metabolic profile, featuring metabolic dysfunction-associated fatty liver disease (MAFLD). MAFLD may determine liver fibrosis progression in GD patients on stable ERT and may be a risk factor for long-term liver-related complications

    An integrative in silico methodology for the identification of modulators of macrophage migration inhibitory factor (MIF) tautomerase activity

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    Macrophage migration inhibitory factor (MIF) is a major proinflammatory cytokine that has been increasingly implicated in the pathogenesis of several inflammatory, autoimmune, infectious and oncogenic diseases. Accumulating evidence suggests that the tautomerase activity of MIF plays a role in modulating some of its intra- and extra-cellular activities. Therefore, the identification and development of small-molecule inhibitors targeting the catalytic activity of MIF has emerged as an attractive and viable therapeutic strategy to attenuate its function in health and disease. Herein we report a novel virtual screening protocol for the discovery of new inhibitors of MIF's tautomerase activity. Our protocol takes into account the flexibility and dynamics of the catalytic site by coupling molecular dynamics (MD) simulations aimed at modeling the protein's flexibility in solution to (i) docking with FlexX, or (ii) docking with FlexX and pharmacophoric filtering with Unity. In addition, we applied in parallel a standalone docking using the new version of Surflex software. The three approaches were used to screen the ChemBridge chemical library and the inhibitory activity of the top-ranked 333 compound obtained from each approach (1000 compound in total) was assessed in vitro using the tautomerase assay. This biochemical validation process resulted in the identification of 12 novel MIF inhibitors corresponding to a 1.2% hit rate. Six of these hits came from Surflex docking; two from FlexX docking with MD simulations and four hits were identified with MDS and pharmacophore filtering with minimal overlap between the hits from each approach. Six hits were identified with IC50 values lower than 10 microM (three hits with IC50 lower than 1 microM); four were shown to be suicide inhibitors and act via covalent modification of the N-terminal catalytic residues Pro1. One additional inhibitor, N-phenyl-N-1,3,4-thiadiazol-2-yl-thiourea, (IC50=300 nM) was obtained from FlexX docking combined to pharmacophoric filtering on one of the eight MD structures. These results demonstrate the power of integrative in silico approaches in the discovery of new modulator of MIF's tautomerase activity. The chemical diversity and mode of action of these compounds suggest that they could be used as molecular probes to elucidate the functions and biology of MIF and as lead candidates in drug developments of anti-MIF drugs
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