Glycogen Synthase Kinase-3β Inhibition Attenuates the Development of Bleomycin-Induced Lung Injury:

Glycogen synthase kinase-3 (GSK-3) is an ubiquitous serine-threonine protein kinase that participates in a multitude of cellular processes and has recently been implicated in the pathophysiology of a number of diseases. The aim of this study is to investigate the effects of TDZD-8, a potent and selective GSK-3β inhibitor, on the development of lung injury caused by administration of bleomycin (BLM). Mice subjected to intra-tracheal administration of BLM developed significant lung injury characterized by marked neutrophil infiltration and tissue edema. An increase in immunoreactivity to nitrotyrosine, iNOS, TNF-α and IL-1β was also observed in the lungs of BLM-treated mice. In contrast, administration of BLM-treated mice with TDZD-8 (1 mg/kg daily) significantly reduced (I) the degree of lung injury, (II) the increase in staining (immunohistochemistry) for myeloperoxidase (MPO), nitrotyrosine, iNOS, TNF-α and IL-1β and (III) the degree of apoptosis, as evaluated by Bax and Bcl-2 immunoreactivity and TUNEL staining. Taken together, these results clearly demonstrate treatment with the GSK-3β inhibitor TDZD-8 reduces the development of lung injury and inflammation induced by BLM in mice

N -Thiocarbazole-based gold nanoparticles: synthesis, characterization and anti-proliferative activity evaluation

Carbazoles are aromatic heterocyclic compounds derived from the fusion of a benzene ring with an indole nucleus in 2,3 position. Today, many carbazole derivatives are widely studied as anticancer, anti-fungal, antioxidants, photoconductor, anti-bacterial, antimalarials, anti-Alzheimer, anti-tuberculosis, anti-HIV agents and for the treatment of obesity. Some of them, differently substituted on carbazole nucleus, have been synthetized and their biological activity have been evaluated. The purpose of this work is the study of new species obtained binding, a series of carbazole derivatives in which the carbazolic nitrogen has been functionalized with different alkyl-thiol chains, with gold nanoparticles, synthesized in organic solvent. The formation of self-assembled monolayers of these ligands is obtained on the spherical surface of gold nanoparticles, with a stabilizing effect against aggregation. These systems might present a double innovative function, matching an antineoplastic activity typical of carbazoles, with the photothermal effects of gold nanoparticles

Probiotics in the add-on treatment of otitis media in clinical practice

Otitis media (OM) affects the middle ear and is typically characterized by earache. OM may be classified as acute (AOM) or chronic (COM), based on symptom duration. OM may be clinically suspected, but the diagnosis is usually confirmed by the otoscopy. Antibiotic therapy is frequently used in clinical practice. However, antibiotics often induce intestinal and respiratory dysbiosis associated with some clinical problems. A one-month course of a probiotic mixture (Abincol® containing Lactobacillus plantarum LP01 (1 billion of living cells), Lactobacillus lactis subspecies cremoris LLC02 (800 million living cells), and Lactobacillus delbrueckii LDD01 (200 million living cells), was prescribed in the Group A, and was compared with no addon treatment, such as the Group B. Patients were evaluated at baseline (T0), at the end of antibiotic treatment (T1), at the end of probiotic course (T2), and at the end of 3-month follow-up (T3)

Effects of zileuton and montelukast in mouse experimental spinal cord injury

Background and purpose: 5-lipoxygenase (5-LO) is the key enzyme in leukotriene (LT) biosynthesis from arachidonic acid (AA). Here, we examined the role of the 5-LO-product, cysteinyl-LT (Cys-LT), with a 5-LO inhibitor (zileuton) and a Cys-LT, receptor antagonist (montelukast), in the inflammatory response and tissue injury associated with spinal cord injury (SCI). Experimental approach: SCI was induced in mice by the application of vascular clips to the dura via a two-level T6 to T7 laminectomy for 1 min. Cord inflammation was assessed histologically and by measuring inflammatory mediators (ELISA) and apoptosis by annexin V, TUNEL, Fas ligand staining and Bax and Bcl-2 expression (immunohistochemistry and western blots). Motor function in hindlimbs was assessed by a locomotor rating scale, for 10 days after cord injury. Key results: SCI in mice resulted in tissue damage, oedema, neutrophil infiltration, apoptosis, tumour necrosis-α (TNF-α) and cyclooxygenase-2 (COX-2) expression, prostaglandin E 2 (PGE 2) and leukotriene B 4 (LTB 4) production, and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation in injured tissue. Treatment of the mice with zileuton or montelukast reduced the spinal cord inflammation and tissue injury, neutrophil infiltration, TNF-α, COX-2 and pERK1/2 expression, PGE 2 and LTB 4 production, and apoptosis. In separate experiments, zileuton or montelukast significantly improved the recovery of limb function over 10 days. Conclusions and implications: Zileuton and montelukast produced a substantial reduction of inflammatory events associated with experimental SCI. Our data underline the important role of 5-LO and Cys-LT in neurotrauma