Norepinephrine Protects against Methamphetamine Toxicity through β2-Adrenergic Receptors Promoting LC3 Compartmentalization

Norepinephrine (NE) neurons and extracellular NE exert some protective effects against a variety of insults, including methamphetamine (Meth)-induced cell damage. The intimate mechanism of protection remains difficult to be analyzed in vivo. In fact, this may occur directly on target neurons or as the indirect consequence of NE-induced alterations in the activity of trans-synaptic loops. Therefore, to elude neuronal networks, which may contribute to these effects in vivo, the present study investigates whether NE still protects when directly applied to Meth-treated PC12 cells. Meth was selected based on its detrimental effects along various specific brain areas. The study shows that NE directly protects in vitro against Meth-induced cell damage. The present study indicates that such an effect fully depends on the activation of plasma membrane β2-adrenergic receptors (ARs). Evidence indicates that β2-ARs activation restores autophagy, which is impaired by Meth administration. This occurs via restoration of the autophagy flux and, as assessed by ultrastructural morphometry, by preventing the dissipation of microtubule-associated protein 1 light chain 3 (LC3) from autophagy vacuoles to the cytosol, which is produced instead during Meth toxicity. These findings may have an impact in a variety of degenerative conditions characterized by NE deficiency along with autophagy impairment.     

Cyanobacteria,Cyanotoxins, and Neurodegenerative Diseases: Dangerous Liaisons

The prevalence of neurodegenerative disease (ND) is increasing, partly owing to extensions in lifespan, with a larger percentage of members living to an older age, but the ND aetiology and pathogenesis are not fully understood, and effective treatments are still lacking. Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis are generally thought to progress as a consequence of genetic susceptibility and environmental influences. Up to now, several environmental triggers have been associated with NDs, and recent studies suggest that some cyanotoxins, produced by cyanobacteria and acting through a variety of molecular mechanisms, are highly neurotoxic, although their roles in neuropathy and particularly in NDs are still controversial. In this review, we summarize the most relevant and recent evidence that points at cyanotoxins as environmental triggers in NDs development.     

Multiparameter Evaluation of the Platelet-Inhibitory Effects of Tyrosine Kinase Inhibitors Used for Cancer Treatment

Current antiplatelet drugs for the treatment of arterial thrombosis often coincide with increased bleeding risk. Several tyrosine kinase inhibitors (TKIs) for cancer treatment inhibit platelet function, with minor reported bleeding symptoms. The aim of this study was to compare the antiplatelet properties of eight TKIs to explore their possible repurposing as antiplatelet drugs. Samples of whole blood, platelet-rich plasma (PRP), or isolated platelets from healthy donors were treated with TKI or the vehicle. Measurements of platelet aggregation, activation, intracellular calcium mobilization, and whole-blood thrombus formation under flow were performed. Dasatinib and sunitinib dose-dependently reduced collagen-induced aggregation in PRP and washed platelets; pazopanib, cabozantinib, and vatalanib inhibited this response in washed platelets only; and fostamatinib, axitinib, and lapatinib showed no/limited effects. Fostamatinib reduced thrombus formation by approximately 50% on collagen and other substrates. Pazopanib, sunitinib, dasatinib, axitinib, and vatalanib mildly reduced thrombus formation on collagen by 10–50%. Intracellular calcium responses in isolated platelets were inhibited by dasatinib (>90%), fostamatinib (57%), sunitinib (77%), and pazopanib (82%). Upon glycoprotein-VI receptor stimulation, fostamatinib, cabozantinib, and vatalanib decreased highly activated platelet populations by approximately 15%, while increasing resting populations by 39%. In conclusion, the TKIs with the highest affinities for platelet-expressed molecular targets most strongly inhibited platelet functions. Dasatinib, fostamatinib, sunitinib, and pazopanib interfered in early collagen receptor-induced molecular-signaling compared with cabozantinib and vatalanib. Fostamatinib, sunitinib, pazopanib, and vatalanib may be promising for future evaluation as antiplatelet drugs.     

Monogenic Autoinflammatory Diseases: State of the Art and Future Perspectives

Systemic autoinflammatory diseases are a heterogeneous family of disorders characterized by a dysregulation of the innate immune system, in which sterile inflammation primarily develops through antigen-independent hyperactivation of immune pathways. In most cases, they have a strong genetic background, with mutations in single genes involved in inflammation. Therefore, they can derive from different pathogenic mechanisms at any level, such as dysregulated inflammasome-mediated production of cytokines, intracellular stress, defective regulatory pathways, altered protein folding, enhanced NF-kappaB signalling, ubiquitination disorders, interferon pathway upregulation and complement activation. Since the discover of pathogenic mutations of the pyrin-encoding gene MEFV in Familial Mediterranean Fever, more than 50 monogenic autoinflammatory diseases have been discovered thanks to the advances in genetic sequencing: the advent of new genetic analysis techniques and the discovery of genes involved in autoinflammatory diseases have allowed a better understanding of the underlying innate immunologic pathways and pathogenetic mechanisms, thus opening new perspectives in targeted therapies. Moreover, this field of research has become of great interest, since more than a hundred clinical trials for autoinflammatory diseases are currently active or recently concluded, allowing us to hope for considerable acquisitions for the next few years. General paediatricians need to be aware of the importance of this group of diseases and they should consider autoinflammatory diseases in patients with clinical hallmarks, in order to guide further examinations and refer the patient to a specialist rheumatologist. Here we resume the pathogenesis, clinical aspects and diagnosis of the most important autoinflammatory diseases in children.     

Hepatic and Extrahepatic Sources and Manifestations in Endoplasmic Reticulum Storage Diseases

Alpha-1-antitrypsin (AAT) and fibrinogen are secretory acute phase reactant proteins. Circulating AAT and fibrinogen are synthesized exclusively in the liver. Mutations in the encoding genes result in conformational abnormalities of the two molecules that aggregate within the rough endoplasmic reticulum (RER) instead of being regularly exported. That results in AAT-deficiency (AATD) and in hereditary hypofibrinogenemia with hepatic storage (HHHS). The association of plasma deficiency and liver storage identifies a new group of pathologies: endoplasmic reticulum storage disease (ERSD).     

Inflammatory Cutaneous Diseases in Renal Transplant Recipients

Kidney transplant recipients frequently suffer from skin infections and malignancies, possibly due to the effects of long-term immunosuppressive therapy. While the relationships between immunosuppression and these pathological conditions have been widely investigated, little is known about the relative incidence and characteristics of inflammatory skin diseases in this type of patient. In this study, we analyze the incidence of a number of inflammatory cutaneous diseases in a cohort of patients who underwent kidney transplantation. Although our study shows a relatively low incidence of these pathologies in transplanted patients—in agreement with the general action of immunosuppressant therapies in reducing inflammation—we scored a different efficacy of the various immunosuppressive regimens on inflammatory and autoimmune skin diseases. This information can be key for designing immunosuppressive regimens and devising accurate follow-up protocols.     

Identification and Optimization of Microbial Attractants for <Emphasis Type="Italic">Philornis downsi</Emphasis>, an Invasive Fly Parasitic on Galapagos Birds

We investigated the role of olfactory cues from actively fermenting yeast (Saccharomyces cerevisiae) in attraction of adult Philornis downsi and identified two synergistically attractive yeast volatiles. Larvae of this invasive fly parasitize the hatchlings of passerines and threaten the Galapagos avifauna. Gas chromatography coupled with electroantennographic detection (GC-EAD), coupled gas chromatography-mass spectrometry (GC-MS), and field trapping experiments were used to identify volatile compounds from a yeast-sugar solution. EAD responses were consistently elicited by 14 yeast volatiles. In a series of field trapping experiments, a mixture of the 14 EAD-active compounds was similarly attractive to P. downsi when compared to the yeast-sugar solution, and we found that acetic acid and ethanol were essential for attraction. A mixture of 0.03 % acetic acid and 3 % ethanol was as attractive as the 14-component blend, but was not as attractive as the yeast-sugar solution. Philornis downsi showed positive and negative dose-responses to acetic acid in the ranges of 0.01 ~ 0.3 % and 0.3 ~ 9 %, respectively. Further optimization showed that the mixture of 1 % acetic acid and 3 % ethanol was as attractive as the yeast-sugar solution. Both mixtures of acetic acid and ethanol were more selective than the yeast-sugar solution in terms of non-target moths and Polistes versicolor wasps captured. These results indicate that acetic acid and ethanol produced by yeasts are crucial for P. downsi attraction to fermented materials on which they feed as adults and can be used to manage this invasive fly in Galapagos.     

A comprehensive investigation of dye–chitosan blended films for green chemistry applications

In this paper, the ability of chitosan film to remove dyestuff from wastewater was evaluated for environmental applications, using three commercial direct azo dyes. Two chitosan films were adopted: the standard one prepared following a well‐known procedure to form it, and a novel one, with a weakly acidic character. Moreover, to improve the adsorption process, the hydrophobic character of the films was investigated. The pH of the dye solutions was also changed, showing an excellent ability in dye removal at pH 12. The films were characterized by means of spectroscopic and morphologic methods to better understand the nature of interactions between dyes and chitosan chains. Swelling ratio measurements were also performed. All analyses suggest that all dyes showed a strong affinity to chitosan polymer chains, with the presence of extended hydrogen bonds and Van der Waals forces perturbing the chitosan network. Interestingly, very good results were obtained in recycling experiments related to the dyeing capacities of chitosan blended films in the presence of textiles. An ecofriendly application is thus presented in this paper. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45945.     

A fan‐equipped reactor for dust explosion tests

A Computational Fluid Dynamics (CFD) model was developed with the aim at simulating the turbulent flow field and associated dust dispersion in an agitated spherical explosion vessel. Simulations were performed in the presence of two counter‐rotating fans and also after having switched‐off the fans. Numerical results have shown that the dust mainly accumulates at the center of the sphere in the space left by the four vortices formed. After the switch‐off of the fans, the dust particles start filling the empty volumes inside the sphere, reaching a quite uniform distribution (with concentration equal to the nominal value) and simultaneously ensuring a controlled value of turbulent kinetic energy. © 2015 American Institute of Chemical Engineers AIChE J, 61: 1572–1580, 2015     

Use of ionic liquids based on phosphonium salts for preparing biocomposites by in situ polymerization

A sodium montmorillonite, Dellite HPS, was modified with ionic liquids based on phosphonium salts, such as octadecyltriphenylphosphonium tetrafluoroborate and octadecyltriphenylphosphonium bromide. Thanks to their high thermal stability, these salts can be used during in situ polymerization, a method that favors the achievement of a good dispersion of the clay. Poly(1,4‐dimethylcyclohexane adipate) (PCHA), was chosen as an example of aliphatic polyester which can be a suitable matrix for new biocomposites with organo‐clays. The organo modified clays prepared were characterized by X‐ray diffraction (XRD), ATR‐FTIR spectroscopy, and thermal gravimetric analysis (TGA) while biocomposites were analyzed in terms of molecular structure, thermal and thermomechanical properties. The degree of dispersion of the clays in the polymer matrix was studied by XRD. The results show that the clays are well dispersed in the biocomposites, despite an intercalated structure highlighted by XRD analysis. Moreover, the clays confer a certain improvement in mechanical properties to the final materials. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42467.