metallothionein and Communicable-Diseases

Arsenic compounds belong to the most controversial agents concerning human health. Arsenic (As) is considered as a top environmental element influencing human health due to its adverse effects including cancer, diabetes, cardiovascular disease, and reproductive or developmental problems. Despite the proven mutagenic, teratogenic and carcinogenic effects, the arsenic compounds are used for centuries to treat infectious diseases. In our work, we focused on studying of interactions of As(III) and/or As(V) with DNA. Interactions between arsenic ions and DNA were monitored by UV/vis spectrophotometry by measuring absorption and fluorescence spectra, atomic absorption spectrometry, electrochemical measurements (square wave voltammetry) and agarose gel electrophoresis. Using these methods, we observed a stable structure of DNA with As(III) within the concentration range 0.4-6.25 μg mL(-1). Higher As(III) concentration caused degradation of DNA. However, similar effects were not observed for As(V).

Topics: Antineoplastic Agents; Arsenic; Communicable Diseases; DNA; DNA Fragmentation; Humans; Ions; Metallothionein; Spectrophotometry, Atomic

Abnormal increments of pro-inflammatory cytokines (IL-6 and TNF-alpha) characterize the outbreak of infectious diseases, which are the major cause of death in the elderly. A counterbalance to the inflammation is exerted by IL-10 with an inhibitory role on TNF-alpha production. As is well known, some cytokine gene polymorphisms influence the cytokine production, playing a role as susceptibility or resistance factors against immune-mediated and infectious disease. Genetic variations in the -308A/G locus for TNF-alpha seems to affect the clinical outcome of some infectious diseases. In fact, the -308A allele is associated with severe septic shock and death. On this basis, we have screened healthy old subjects, nonagenarians and old patients affected by the acute phase of chronic obstructive bronchitis and bronchopneumonia of bacteria origin for the -308G/A locus (PCR-RFLP). Subjects are grouped in A+ (AG, AA genotypes) and A- (GG genotype) and data on IL-6, TNF-alpha, IL-10, NK cell cytotoxicity, zinc and metallothioneins (MTs) gene expression (RT-PCR) were stratified according to different TNF-alpha genotypes. The frequency of the A allele was increased in infected patients in comparison with healthy old controls. No differences existed between A+ and A- young adult, old and nonagenarian controls in tested parameters. Conversely, A+-infected patients displayed elevated IL-6, TNF-alpha and MTmRNA, low IL-10 coupled with impaired NK cell cytotoxicity and lower zinc ion than A- patients. However, the data reported are gender independent. Therefore, the -308A polymorphism at the locus of TNF-alpha may be one of the susceptibility factor for infectious diseases in old persons, particularly considering its association to the increased release of pro-inflammatory cytokines and to the reduction of zinc release and MTs synthesis involved in the control of the inflammatory response. These data strongly suggest that the genetic screening of the -308G/A polymorphism may be a valid tool for identification of subjects needing a more appropriate therapy when affected by acute and/or recurrent infectious diseases.

Topics: Adult; Aged; Bronchitis, Chronic; Bronchopneumonia; Communicable Diseases; Female; Gene Frequency; Genotype; Humans; Interleukin-6; Killer Cells, Natural; Male; Metallothionein; Middle Aged; Polymorphism, Genetic; Tumor Necrosis Factor-alpha; Zinc