The modulation of attachment,growth and morphology of cancerous prostate cells by polyelectrolyte nanofilms

The behaviour of cancerous epithelial prostatic cells (PC3) growing on polyelectrolytes (PE) coatings was compared to the behaviour of immortalized normal prostatic cells (PNT-2). The cell behaviour was evaluated and quantified in terms of initial cell attachment, growth, metabolic activity, morphometry, adhesion, apoptosis and stress related gene expression. Both the anionic PSS (poly(sodium 4-styrenesulphonate))-terminated surface and cationic PAH (poly(allylamine hydrochloride))-terminated surfaces were not cytotoxic. The initial attachment of cells was better on the PAH-terminated surface compared to fibronectin. However, the proliferation rate of PC3 cells was reduced on the PAH-terminated surface and slightly increased on the PSS coatings. Only PAH prevented the clustering phenotype of PC3 and reduced the number of focal adhesion points as compared to fibronectin or PSS coatings. In contrast, none of the PE surfaces significantly affected the biological responses of PNT-2 cells. PAH-terminating films provide a tool to preferentially modulate the growth of some cancerous phenotypes, in this case as a micro-environment that reduces the growth of metastatic PC3 cells.     

Clinical correlate of brain SPECT perfusion abnormalities in fibromyalgia

The purpose of this study was to investigate the specific clinical correlate of brain SPECT perfusion abnormalities reported in fibromyalgia. METHODS: We performed a whole-brain voxel-based correlation analysis involving regional cerebral blood flow and various parameters related to pain (Visual Analog Scale, Tubingen Pain Behavior Scale, and Questionnaire Douleur de Saint-Antoine Scale), disability (Fibromyalgia Impact Questionnaire [FIQ]), and anxiety and depression status (Hospital Anxiety and Depression scale) in 20 patients with fibromyalgia (P voxel < 0.005). Ten healthy control women were also included, in order to determine areas of significant hypo- and hyperperfusions in patients. RESULTS: FIQ total score was positively correlated with bilateral parietal perfusion, including postcentral cortex. These clusters of correlation were included in the areas of significant hyperperfusion. FIQ total score was also negatively correlated with perfusion of a left anterior temporal cluster, included in the areas of significant hypoperfusions. No other clinical correlation was observed with regional cerebral blood flow. CONCLUSION: These results show that brain perfusion abnormalities in patients with fibromyalgia are correlated with the clinical severity of the disease.     

Arylamine N-acetyltransferase activity in bronchial epithelial cells and its inhibition by cellular oxidants

Bronchial epithelial cells express xenobiotic-metabolizing enzymes (XMEs) that are involved in the biotransformation of inhaled toxic compounds. The activities of these XMEs in the lung may modulate respiratory toxicity and have been linked to several diseases of the airways. Arylamine N-acetyltransferases (NAT) are conjugating XMEs that play a key role in the biotransformation of aromatic amine pollutants such as the tobacco-smoke carcinogens 4-aminobiphenyl (4-ABP) and β-naphthylamine (β-NA). We show here that functional human NAT1 or its murine counterpart Nat2 are present in different lung epithelial cells i.e. Clara cells, type II alveolar cells and bronchial epithelial cells, thus indicating that inhaled aromatic amines may undergo NAT-dependent biotransformation in lung epithelium. Exposure of these cells to pathophysiologically relevant amounts of oxidants known to contribute to lung dysfunction, such as H₂O₂ or peroxynitrite, was found to impair the NAT1/Nat2-dependent cellular biotransformation of aromatic amines. Genetic and non genetic impairment of intracellular NAT enzyme activities has been suggested to compromise the important detoxification pathway of aromatic amine N-acetylation and subsequently to contribute to an exacerbation of untoward effects of these pollutants on health. Our study suggests that oxidative/nitroxidative stress in lung epithelial cells, due to air pollution and/or inflammation, could contribute to local and/or systemic dysfunctions through the alteration of the functions of pulmonary NAT enzymes.     

Age-related macular degeneration: Current and novel therapies

Age-related macular degeneration (AMD) is a leading cause of vision loss in people over the age of 60 with a prevalence that continues to rise, particularly in industrialized nations. Although treatments for AMD were once limited, with disappointing clinical results, new treatments have emerged for both the nonexudative and exudative forms of the disease, which have improved prognostic outcomes. These treatments include nutritional supplementation, antioxidant prophylaxis, and intravitreal injection of medications that inhibit aberrant vascular proliferation. This review serves as a summary of the current and experimental therapies for both exudative and nonexudative AMD. Although a number of challenges and clinical questions remain, the future of treating AMD appears promising particularly as we gain further insights into the genetic and biochemical pathways of the disease.