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Oxygen transport is optimized at the cellular level, since oxygen serves as the terminal electron acceptor in mitochondrial oxidative phosphorylation and several enzymatic processes require molecular oxygen as substrate. During development and aging, redundant cells and exhausted cells are eliminated, respectively, whereas others can adapt to the stressful environment and survive. The study investigated the molecular mechanisms activated in the lung during normal aging, through the expression of hypoxia inducible factor (HIF), vascular endothelial growth factor (VEGF), p53, p66Shc, putative cysteine protease (CPP32) and kinaseB-α phosphorylation (pIkB-α). Twelve male Wistar rats divided into two age-groups, each consisting of 6 animals, 3 and 24 months old, were used. The rats were anesthetized with Nembutal (40 mg/kg, ip) and the lungs were excised from each rat and processed for TUNEL and Western blotting analyses. The expressions of p53, p66Shcand CPP32 were significantly increased in the old normoxic rat lung specimens, when compared with the young ones. In parallel, expressions of VEGF and pIkBα were increased in old rather than young rats. Aging leads to increased expressions of p53, p66Shcand CPP32, suggesting that apoptosis is in progress. At the same time, the lung tries to counteract apoptosis through the production of VEGF and pIkB-α to adapt itself to a stressful situation. The aging lung creates a life-support system in order to counteract the apoptotic process.

Nutrient composition, particularly the omega-6/omega-3 polyunsaturated fatty acids ratio, may differently affect inflammatory mediators production in tissues, which could be causally related to increased cancer incidence in obesity. We evaluated prostaglandin E2levels in male Wistar rat prostate, kidney and testicle tissues after 15 days of either a high fat, cafeteria-style diet (5.50 Kcal/g, 30% calories from fat, omega-6/omega-3 ratio 2.33) or a standard laboratory chow diet (3.35 Kcal/g, 3% calories from fat, omega-6/omega-3 ratio 0.56). In the cafeteria diet compared to standard laboratory diet rats, we found both an increase in weight gain and increased prostaglandin E2(PGE2) levels in prostate, kidney and testicle tissues. The increased levels of PGE2induced by the cafeteria diet could drive an inflammatory process leading to increased incidence of prostate, kidney and testicular cancer in overweight patients.

The aim of the present study is to investigate oxidative stress produced by experimental hypoxia and hyperoxia in young and old pampiniform plexus rats, in order to evaluate the oxidative role of oxygen. Oxidative stress causing molecular and cellular dysfunction increases in hypertension and can therefore be considered a state of oxidative stress. This consideration makes us reflect on the responsibility of oxidative stress in the veins of the pampiniform plexus, notoriously under high hydrostatic pressure. After experimental hypoxia and hyperoxia we studied the 8-iso-PGF2alpha release (a specific index of cellular oxidative stress) in young and old left pampiniform plexus rats. The basal 8-iso-PGF2alpha release showed a statistically significant difference P=0.0067 between young and old rats PP. After hypoxia and hyperoxia, the release was higher in young rats as compared to normoxia, respectively P=0.0001 and P=0.0002. After hypoxia the release was not modified in old rats P=0.544 while after hyperoxia the release was increased in old rats as compared to control P<0.0001. The results show how chronic hypoxia and hyperoxia represent two important causes of oxidative stress and lipid peroxidation in pampiniform plexus rats. In young rats an increase of oxidative stress suggests that pampiniform plexus is sensitive to variations of oxygen supply. In old rats the pampiniform plexus is liable to a reduction of oxygen-sensing mechanisms and it is possible that the missing oxidative answer to the hypoxia in old rats is attributable in all likelihood to adaption to a hypoxic condition typical of aging.

The skeleton is the third most common site for cancer to spread after the liver and lungs. Malignancies that can cause destruction of skeletal bones include multiple myeloma and metastatic diseases of the lung, prostate and other solid cancers. The clinical complications include pain, fractures, compression of the spinal cord and hypercalcemia of malignancy. Bisphosphonates are bone-seeking agents originally designed to treat loss of bone density. Accumulating data show that they are effective in diseases in which there is upregulation of osteoclastic or osteolytic activity. Bisphosphonates can reduce skeletal-related events and bone pain, as well as reduce the adverse effects of androgen deprivation therapy on skeletal integrity. However, it is clear that bisphosphonates do not represent a decisive treatment in the care of metastases but a therapeutic choice in synergy with regular anti-tumor drugs. The preclinical and clinical data to support this are reviewed here.