Insulin Activation Mediated by Uptake Mechanisms: A Comparison of the Behavior between Polymer Nanoparticles and Extracellular Vesicles in 3D Liver Tissues.

In this work, we compare the role of two different uptake mechanisms in the effectiveness of a nanoformulated drug, specifically insulin. Insulin is activated by interacting with insulin receptors exposed on the liver cell membrane that triggers the uptake and storage of glucose. To prove that the uptake mechanism of a delivery system can interfere directly with the effectiveness of the delivered drug, two extremely different delivery systems are tested. In detail, hydrogel-based NPs (cHANPs) and natural lipid vesicles (EVs) encapsulating insulin are used to trigger the activation of this hormone in 3D liver microtissues (µTs) based on their different uptake mechanisms. Results demonstrated that the fusion mechanism of Ins-EVs mediates faster and more pronounced insulin activation with respect to the endocytic mechanism of Ins-cHANPs. Indeed, the fusion causes an increased reduction in glucose concentration in the culture medium EV-treated l-µTs with respect to free insulin-treated tissues. The same effect is not observed for Ins-cHANPs that, taken up by endocytosis, can only equal the reduction in glucose concentration produced by free insulin in 48 h. Overall, these results demonstrate that the effectiveness of nanoformulated drugs depends on the identity they acquire in the biological context (biological identity). Indeed, the nanoparticle (NP) biological identity, such as the uptake mechanism, triggers a unique set of nano-bio-interactions that is ultimately responsible for their fate both in the extracellular and intracellular compartments.

A retrospective observational study comparing somatosensory amplification in fibromyalgia, chronic pain, psychiatric disorders and healthy subjects.

OBJECTIVES: Somatosensory amplification (SA) has been described as an important feature of somatoform disorders, and an "amplifying somatic style" has been reported as a negative connotation of body perception. As widespread pain (WSP) in fibromyalgia (FM) is due to a central sensitization (CS) rather than organic alterations, there has been discussion as to whether FM is equivalent to or distinct from somatization disorder (SD). Assuming SD and FM are two distinct entities, an increase in somatic amplification should be expected only in subjects who have SD, regardless of the type of pain they experience. Purpose of the study was to explore the magnitude of SA in FM, and whether this depends on the association with SD. METHODS: FM (n=159) other forms of chronic pain (OCP, n=582), psychiatric (Psy, n=53) and healthy (H, n=55) subjects were investigated using the Somatosensory Amplification Scale (SSAS), Illness Behavior Questionnaire, (IBQ), Italian Pain Questionnaire (IPQ), and Cold Pressor Test (CPT) in a retrospective observational study. RESULTS: FM subjects displayed higher SSAS scores than the other groups. High SSAS score was associated with FM (OR=8.39; 95%CI: 5.43-12.46) but not OCP. Although FM has the highest prevalence of SD (x2=14.07; p=.007), high SSAS scores were associated with SD in OCP but not in FM. CONCLUSIONS: Unlike in OCP, in FM high SSAS scores were independent of the presence of SD. From a biopsychosocial perspective, SSAS may be a factor associated with the onset of FM.

[Extra-hepatic manifestations associated with Hepatitis and virus infection].

Hepatitis E virus (HEV) is a significant public health problem that affects almost 20 million individuals annually and cause acute liver injury in 3,5 million. Hepatitis E virus can cause acute, fulminant and chronic hepatitis and has been associated with a range of extrahepatic manifestation. The spectrum of these manifestation is still emerging. Acute pancreatitis and neurological, renal, hematologic, and muscoloskeletal manifestations have been described. Renal injury include membranoproliferative glomerulonephritis with or without cryoglobulinemia, membranous glomerulonephritis and tubular necrosis. The etiopathogenesis of extrahepatic manifestation is only supposed. It could be caused by a direct tossic effect of HEV or by an autoimmune process. We report a case of a 46 years old man who presented with acute hepatitis E. He was diagnosed to have acute severe renal failure and severe pancreatitis due to hepatitis E. Few cases have been reported in the literature concerning patients suffering from hepatitis E and severe extraepatic manifestations with a benign course and complete recovery.

[Therapy of glucocorticoid induced osteoporosis]. / Terapia dell'osteoporosi da glucocorticoidi.

Glucocorticoid-induced osteoporosis (GIO) is a major cause of secondary osteoporosis that starts early after the beginning of therapy even for low drug doses. Glucocorticoids are used for the treatment of immunologic nephropathies and in the setting of kidney transplant. In clinical practice, a number of algorithms are available; they allow us to estimate the long-term risk of major osteoporotic fracture; but none of them is specific for GIO. To date, the therapeutic approach comprises both general measures aimed at correcting calcium and vitamin D intake, and drugs (bisphosphonates, teriparatide, hormone replacement therapy, denosumab) that ameliorate bone mineral density and patient outcomes.

[Acute hepatotoxicity from intravenous amiodarone in a patient on hemodialysis]. / Epatotossicità acuta da amiodarone endovena in una paziente in emodialisi.

Amiodarone is a class III antiarrhythmic drug used to treat several tachyarrhythmias. Although toxicity by long-term oral therapy is known, it is rare to observe the acute toxicity correlated to intravenous use. We report an unusual case of acute hepatotoxicity after the initiation of intravenous amiodarone for atrial fibrillation in a patient on regular hemodialysis. Liver enzymes progressively decreased and normalized upon discontinuing the drug. As a result, closely monitoring of liver enzyme is suggested when intravenous amiodarone is prescribed.

[Severe neutropenia during treatment with amoxicillin/clavulanic acid in a patient on regular hemodialysis treatment]. / Severa neutropenia durante trattamento con amoxicillina/acido clavulanico in un paziente in trattamento emodialitico regolare.

Beta-lactams are one of the most widely used antibiotics in respiratory diseases, both in adults and in the pediatric population. Their widespread use is also linked to the elevated tolerability and low risk of side effects that are generally not severe. We present here the case of a patient on regular haemodialysis pertaining to our Center who, after a seven-day treatment period with amoxicillin/clavulanic acid antibiotic therapy (medication originator), developed a framework of severe neutropenia (neutrophils till 10/mmc) resulting in hospitalization and the beginning of a specific diagnostic and therapeutic work-up. Our case is characterised, differently from other reports in the literature, for the onset of neutropenia after a short course of antibiotics, with a drug already used in the past without any side effects. During hospitalization, use of immunostimulant therapy led to the rapid recovery of a normal white blood cell count and resolution of severe neutropenia.

Allopurinol, an inhibitor of purine catabolism, enhances susceptibility of tobacco to Tobacco mosaic virus.

Tobacco (cv. Xanthi nn) plants were watered with allopurinol [4-hydroxypyrazolo (3,4-d) pyrimidine, HPP], a xanthine oxidoreductase (XOR) inhibitor, to investigate its effects on infection by Tobacco mosaic virus engineered to express the green fluorescent protein (TMV.GFP). TMV.GFP infection was monitored by examination of inoculated leaves under UV light, by confocal scanning laser microscopy and by epifluorescence microscopy. Susceptibility to TMV.GFP was enhanced in HPP-treated plants. This was seen as a statistically significant increase in numbers of infection sites per leaf and in the number of infected cells per infection site. Two hypotheses are discussed to explain the enhanced susceptibility. The inhibition exerted by HPP against XOR activity could provoke either (i) an increased adenine and guanine nucleotide pool, which could facilitate viral RNA synthesis or (ii) it could cause changes in IAA/auxin levels, which has been proposed to influence TMV susceptibility in tobacco.