Molecular approach to the nucleo-melanosomal interaction in human melanoma cells

This paper presents evidence that L-tyrosine oxidation products and 5,6-dihydroxyindole, an intermediate of melanin synthesis bind to and modify DNA structure, as tested by extracting cell DNA, using topoisomerase I and denaturation assays. When supercoiled plasmid pCU18 or pBR322 DNAs are treated with 5,6-dihydroxyindole the supercoiled species disappear and are converted to species less mobile in a gel retardation test with respect to relaxed DNA. 5,6-Dihydroxyindole causes an easier acid denaturation of the double helix. The results, that are dose dependent,would point to both intercalation and cross-linking of DNA by 5,6-dihydroxyindole and its oxidation product(s). ³H-L-tyrosine deriving radioactivity, bound to nuclear DNA, is higher at low pH, (5.6) if compared to pH 6.8. The highest radioactivity bound to cell DNA is found during the transition from the amelanotic to the melanotic phenotype in human melanoma cell lines. As a control, the binding of ³H-L-tyrosine radioactivity to human prostate fibroblast DNA was investigated.     

Effectiveness of C5 or C6-Cz assembly in predicting immediate post operative facial nerve deficit

Background

Intraoperative neurophysiology monitoring (IOM) is a valuable tool in cerebellopontine angle (CPA) surgeries posing risk to the cranial nerves. Transcranial electrical stimulation (TES) for cranial nerves has been performed in the last 7 years, for obtaining the facial nerve motor evoked potential (MEP), using either C3/C4-Cz or C3-C4 (or inverse) stimulating points, which have been correlated with facial nerve functional outcome.

Method

Intraoperative surgical and electrophysiological findings were documented prospectively. Patient files were reviewed for clinical data. We studied 23 patients undergoing CPA tumor resection using C5 or C6-Cz montage for TES, and were able to determine the correlation between facial nerve functional outcome and the amplitude drop of facial MEP above 50 %. Patients were evaluated for immediate facial nerve outcome and 6 months after the surgery. Follow-up was performed by structured telephone interviews with local physicians.

Results

The sensibility of the studied parameters was 92.8 % for amplitude drop of facial nerve MEP, with positive predictive value of 81.2 %. The absence of changes during IOM has shown a negative predictive value of 100 %.

Conclusion

In this series, the used montage was effective in predicting new facial deficit.     

Cyclooxygenase-1 is involved in endothelial dysfunction of mesenteric small arteries from angiotensin II-infused mice

Angiotensin II induces endothelial dysfunction by reducing NO availability and increasing reactive oxygen species. We assessed whether cyclooxygenase (COX)-1 or COX-2 participate in the angiotensin II-induced endothelial dysfunction in murine mesenteric small arteries and examined the role of reduced nicotinamide-adenine dinucleotide phosphate-dependent reactive oxygen species production. Mice received angiotensin II (600 ng/kg per minute, SC), saline (controls), angiotensin II + apocynin (reduced nicotinamide-adenine dinucleotide phosphate oxidase inhibitor, 2.5 mg/day), or apocynin alone for 2 weeks. Endothelial function of mesenteric arteries was assessed by pressurized myograph. In controls, acetylcholine-induced relaxation was inhibited by NG-monomethyl-L-arginine and unaffected by DFU (COX-2 inhibitor), SC-560 (COX-1 inhibitor), or ascorbic acid. In angiotensin II-infused animals, the attenuated response to acetylcholine was less sensitive to NG-monomethyl-L-arginine, unaffected by DFU, and enhanced by SC-560 and, similarly, by SQ-29548, a thromboxane-prostanoid receptor antagonist. Moreover, response to acetylcholine was unchanged by ozagrel, a thromboxane synthase inhibitor, and normalized by ascorbic acid. Apocynin prevented the angiotensin II-induced vascular dysfunctions. In angiotensin II-infused mice, RT-PCR analysis showed a significant COX-2 downregulation, whereas COX-1 expression was upregulated. These changes were unaffected by apocynin. Modulation of COX isoform by angiotensin II was also documented by immunohistochemistry. In small mesenteric vessels, the reduced NO availability and oxidant excess, which characterize endothelial dysfunction secondary to angiotensin II, are associated with a reduced COX-2 and an increased COX-1 function and expression. Angiotensin II causes an oxidative stress-independent COX-1 overexpression, whereas angiotensin II-mediated oxidant excess production stimulates COX-1 activity to produce a contracting prostanoid endowed with agonist activity on thromboxane-prostanoid receptors.     

Comparative analysis of new innovative vaccine formulations based on the use of procaryotic display systems

A T helper epitope was expressed in three innovative delivery vehicles recently developed in our laboratories and based respectively, on the filamentous bacteriophage fd, the E2 protein from the PDH complex of Bacillus stearothermophilus and the protein CotC of Bacillus subtilis spores. Studies of antigenicity and immunogenicity were performed by using a specific T cell hybridoma and by priming mononuclear cells isolated from the venous blood of human donors. The results indicate that the E2 system is the best suited for inducing a specific immune response towards a CD4 T cell epitope. Importantly, TCR clonal analysis demonstrated the persistence over years of a previously described antigen specific clonotype and its presence correlates with the immunogenic strength of the antigen delivery system.     

Clinical efficacy of esomeprazole in the prevention and healing of gastrointestinal toxicity associated with NSAIDs in elderly patients

NSAIDs are widely prescribed for the treatment of pain, inflammation and rheumatic disorders, but their use is associated with adverse gastrointestinal effects, ranging from dyspeptic symptoms and peptic ulcers to more serious complications. Elderly patients are at high risk of experiencing NSAID-induced gastrointestinal tract injury and should be considered candidates for prophylactic pharmacological therapy. In studies conducted in adult patients, proton pump inhibitors (PPIs) such as esomeprazole have been shown to prevent or reduce NSAID-induced gastrointestinal injury. The beneficial effects of esomeprazole can be ascribed largely to its ability to maintain sustained inhibition of gastric acid secretion, although there is evidence to suggest that pharmacodynamic properties unrelated to acid inhibition may also contribute to the gastroprotective effects of this agent. Although there are limited data on the use of esomeprazole specifically in elderly patient populations, studies of patients at high risk of NSAID-induced gastrointestinal toxicity because of advanced age indicate that this PPI is both effective and well tolerated when administered in conjunction with NSAIDs. Thus, esomeprazole can be regarded as a useful option for prophylactic therapy in elderly patients receiving long-term NSAID therapy.