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1.
J Clin Virol ; 114: 37-42, 2019 05.
Article in English | MEDLINE | ID: mdl-30913521

ABSTRACT

BACKGROUND: Experimental data show that type I interferon has a key role in innate immune response against influenza infection. OBJECTIVE: We compared nasal levels of interferon-α2 and ß among inpatients and outpatients with influenza. STUDY DESIGN: Children younger than 5 years of age with influenza-like illness seeking care at the emergency department within the first 72 h of disease onset were prospectively included. Clinical and demographic data and secretions through nasal wash were obtained. Influenza infection was assessed through reverse-transcription polymerase chain reaction and nasal levels of interferon-α2 and ß were measured by enzyme-linked immunosorbent assay. All patients followed until the end of the disease. RESULTS: One hundred patients were included, of which 24 had confirmed influenza infection, and 5 of them were hospitalized. Subtypes A (H3N2) and B were confirmed in 10 and 14 patients, respectively. Seventy-six patients without influenza, including 48% of outpatients, were recruited as controls. All hospitalized patients were significantly younger regardless of influenza status (age <6 months in 59% vs. 23.2%, p < 0.001). All other data were similar among the groups. Comparing median levels of interferon-α2 among children with influenza, levels were significantly higher in outpatients than in hospitalized patients and were 263.2 pg/mL (25-75 interquartile range: 58.3-634) and detectable in only one patient (90 pg/mL), respectively. The levels of interferon-α2 in controls and those of interferon-ß in all groups were not detected. CONCLUSIONS: Higher levels of interferon-α2 in patients with less severe influenza reinforce experimental evidence about the protective role of interferon-α2 against influenza infection.


Subject(s)
Immunity, Innate , Influenza, Human/immunology , Interferon Type I/analysis , Nose/immunology , Respiratory Tract Infections/immunology , Bodily Secretions/virology , Child, Preschool , Cohort Studies , Female , Hospitalization , Humans , Infant , Influenza A Virus, H3N2 Subtype/genetics , Influenza A Virus, H3N2 Subtype/immunology , Inpatients/statistics & numerical data , Interferon Type I/immunology , Interferon alpha-2/analysis , Interferon alpha-2/immunology , Interferon-beta/analysis , Interferon-beta/immunology , Male , Nose/virology , Outpatients/statistics & numerical data , Respiratory Tract Infections/virology
2.
Bioorg Med Chem Lett ; 27(15): 3238-3242, 2017 08 01.
Article in English | MEDLINE | ID: mdl-28647350

ABSTRACT

Resveratrol (Rsv) is widely reported to possess anticarcinogenic properties in a plethora of cellular and animal models having limited toxicity toward normal cells. In the molecular level, Rsv can act as a suppressive agent for several impaired signaling pathways on cancer cells. However, Fukuhara and Miyata have shown a non-proteic reaction of Rsv, which can act as a prooxidant agent in the presence of copper (Cu), causing cellular oxidative stress accompanied of DNA damage. After this discovery, the complex Rsv-Cu was broadly explored as an antitumor mechanism in multiples tumor cell lines. The aim of the study is to explore the anticarcinogenic behavior of resveratrol-Cu(II) complex in MCF-7 cell line. Selectivity of Rsv binding to Cu ions was analyzed by HPLC and UV-VIS. The cells were enriched with concentrations of 10 and 50µM CuSO4 solution and treated with 25µM of Rsv. Copper uptake after enrichment of cells, as its intracellular distribution in MCF-7 line, was scanned by ICP-MS and TEM-EDS. Cell death and intracellular ROS production were determined by flow cytometry. Different from the extracellular model, no relationship of synergy between Rsv-Cu(II) and reactive oxidative species (ROS) production was detected in vitro. ICP-MS revealed intracellular copper accumulation to both chosen concentrations (0.33±0.09 and 1.18±0.13ppb) but there is no promotion of cell death by Rsv-Cu(II) complex. In addition, significant attenuation of ROS production was detected when cells were exposed to CuSO4 after Rsv treatment, falling from 7.54% of ROS production when treated only with Rsv to 3.07 and 2.72% with CuSO4. Based on these findings antitumor activity of resveratrol when in copper ions presence, is not mediated by Rsv-Cu complex formation in MCF-7 human cell line, suggesting that the antitumoral reaction is dependent of a cancer cellular model.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Copper/chemistry , Copper/pharmacology , Stilbenes/chemistry , Stilbenes/pharmacology , Apoptosis/drug effects , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Humans , MCF-7 Cells , Neoplasms/drug therapy , Neoplasms/metabolism , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Resveratrol
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