Cisplatin is the most common antineoplastic drug used for the therapy of solid tumours. To date, researchers have focused on the dosage to be administered for each specific tumour, mainly considering the local adverse effects. The aim of this study was to correlate the severity of the adverse effects with: i) the dosage of cisplatin; ii) the specific site of the tumour; iii) the association with other drugs; and iv) the symptoms. We analysed data from 123 patients with 11 different tumour classes undergoing therapy from 2007 to 2008 at St. Anna Hospital (Ferrara, Italy), using the Spearman non-parametric correlation index. Even though significant correlations were found among the variables, the overall results showed that the main factor influencing the severity of the adverse effects was the dosage of cisplatin administered.

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Gonad development and sex differentiation from embryos to 594-day-old individuals were investigated in farmed Acipenser naccarii using light and transmission electron microscopy. The migrating primordial germ cells first appear along the dorsal wall of the body cavity in embryos 1.5 days before hatching. The gonadal ridge, containing a few primary primordial germ cells (PGC-1) surrounded by enveloping cells, appears in 16-day-old larvae. At 60 days, the undifferentiated gonad is lamellar and PGC-1 multiply, producing PGC-2. In 105-day-old juveniles, a distinct germinal area with advanced PGC-2 appears on the lateral side near the mesogonium and the first blood vessels are visible. At 180 days, putative ovaries with a notched gonadal epithelium and putative testes with a smooth one appear, together with adipose tissue on the distal side. In 210-day-old juveniles, active proliferation of germ cells begins in the putative ovaries, whereas putative testes still contain only a few germ cells. The onset of meiosis and reorganization of stromal tissue occurs in ovaries of 292-day-old individuals. Ovaries with developed lamellae enclosing early oocyte clusters and follicles with perinucleolar oocytes occur at 594 days. Meiotic stages are never found, even in anastomozing tubular testes of 594-day-old individuals. Steroid producing cells are detected in the undifferentiated gonad and in the differentiated ones of both sexes. Anatomical differentiation of the gonad precedes cytological differentiation and female differentiation largely precedes that of the male. Gonad development and differentiation are also associated with structural changes of connective tissue, viz. collagen-rich areas are massive in developing testes and reduced in ovaries.

Rhinoviruses are the major cause of the common cold and acute exacerbations of asthma and chronic obstructive pulmonary disease. We previously reported rapid rhinovirus induction of intracellular superoxide anion, resulting in NF-B activation and pro-inflammatory molecule production. The mechanisms of rhinovirus superoxide induction are poorly understood. Here we found that the proteolytic activation of the xanthine dehydrogenase/xanthine oxidase (XD/XO) system was required because pretreatment with serine protease inhibitors abolished rhinovirus-induced superoxide generation in primary bronchial and A549 respiratory epithelial cells. These findings were confirmed by Western blotting analysis and by silencing experiments. Rhinovirus infection induced intracellular depletion of reduced glutathione (GSH) that was abolished by pretreatment with either XO inhibitor oxypurinol or serine protease inhibitors. Increasing intracellular GSH with exogenous H 2 S or GSH prevented both rhinovirus-mediated intracellular GSH depletion and rhinovirus-induced superoxide production. We propose that rhinovirus infection proteolytically activates XO initiating a pro-inflammatory vicious circle driven by virus-induced depletion of intracellular reducing power. Inhibition of these pathways has therapeutic potential. Rhinoviruses (RV)3 are the major cause of the commonest human acute infectious disease, the common cold (1). They are also associated with the majority of acute exacerbations of asthma (2, 3) and chronic obstructive pulmonary disease (COPD) (4,5). No licensed effective antiviral is currently available for the treatment of the common cold (6, 7) and treatment of virus-induced asthma and COPD exacerbations is a major unmeet therapeutic need (8). Understanding the mechanisms of virus-induced exacerbation of airway diseases is required to identify molecular targets for therapeutic intervention.The mechanisms underlying virus-induced exacerbations of airway diseases are poorly understood. However, rhinoviruses are believed to directly infect airway epithelium inducing proinflammatory cytokine production (9 -11). This leads to recruitment and activation of inflammatory cells, resulting in airway inflammation (12,13). We have recently demonstrated that bronchial epithelial cells from asthmatic subjects have a deficient innate immune response to rhinovirus infection, responsible for: (i) increased virus replication (14, 15) that could account for increased and more persistent inflammatory responses (12); (ii) increased severity and duration of lower respiratory tract symptoms and reductions in lung function (16) in rhinovirus-induced asthma exacerbations.Increased oxidative stress is implicated in induction of the acute airway inflammation during exacerbations of asthma and COPD (17). Oxidants are directly involved in inflammatory responses via signaling mechanisms, including the redox-sensitive activation of transcription factors such as 19).Recent data indicate that rhinovirus and other respiratory viruses can alter cellular re...

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