دانلود رایگان مقاله انگلیسی درمان اختلال فلوروکینولون وابسته: پیامدهای پاتوبیولوژیک - هینداوی 2017

Long-term fluoroquinolone-associated disability (FQAD) after fluoroquinolone (FQ) antibiotic therapy appears in recent years as a significant medical and social problem, because patients suffer for many years after prescribed antimicrobial FQ treatment from tiredness, concentration problems, neuropathies, tendinopathies, and other symptoms. The knowledge about the molecular activity of FQs in the cells remains unclear in many details. The effective treatment of this chronic state remains difficult and not effective. The current paper reviews the pathobiochemical properties of FQs, hints the directions for further research, and reviews the research concerning the proposed treatment of patients. Based on the analysis of literature, the main directions of possible effective treatment of FQAD are proposed: (a) reduction of the oxidative stress, (b) restoring reduced mitochondrion potential ΔΨm, (c) supplementation of uni- and bivalent cations that are chelated by FQs and probably ineffectively transported to the cell (caution must be paid to Fe and Cu because they may generate Fenton reaction), (d) stimulating the mitochondrial proliferation, (e) removing FQs permanently accumulated in the cells (if this phenomenon takes place), and (f) regulating the disturbed gene expression and enzyme activity.

4. Therapeutic Conclusions

The treatment of the FQAD, especially that lasting for many years, is a very difficult therapeutic problem. The effectiveness of different therapies carried out on patients is rather low. A large number of patients suffers from chronic tiredness, tendinopathies, neuropathies, and lack of sleep, even more than 12 h/24 h. Understanding all the molecular mechanisms of the FQ activity in the cell is the urgent aim for the current science to find methods helping these people.

The main question that arises here concerns the reasons of chronicity of FQAD symptoms which last for many years, sometimes, even after a standard 5-day FQ treatment. 3 reasons can be taken into consideration:

(a) Long-lasting OS destroys the mitochondrial DNA and the newly synthesized proteins creating cytochrome complexes are disturbed in their structure leading to permanent electron leakage and OS.

(b) The complexes of FQ with proteins and cations are so stabile that they exist in the cells by many years disturbing energy production and epigenetics.

(c) Epigenetic changes in gene regulation become persistent many years of FQ application even in the case of lack of FQ in the cell.