![]() ![]() Inclusion criteria were as follows: age: 20–70 years the presence of a venous leg ulcer for a minimum of 6 weeks, as chronic leg ulcers often are defined as those wounds lasting longer than 6 weeks 2. Patients eligible for this study were of both sexes, older than 20 years with chronic venous leg ulcer, evidence of venous reflux at duplex scanning and with no evidence of ischaemia (ankle‐brachial pressure index > 0♹). Before the beginning of this study, all participants provided written informed consent. We performed an open‐label, parallel‐group, single clinical centre study, conducted between January 2010 and October 2012 with prior approval from the Institutional Review Board, in accordance with the Declaration of Helsinki and the Guideline for Good Clinical Practice. In this light, in this study, we evaluated the effects of subantimicrobial doses of doxycycline in patients with chronic venous leg ulcers. Moreover, clinical and experimental studies reported that doxycycline is able to inhibit, at lower doses, the activation of MMPs 14, 15, 16, 17, 18. In particular, tetracyclines are able to affect inflammation, immunomodulation, cell proliferation and angiogenesis and have been used to treat a wide variety of non‐infectious diseases including rheumatoid arthritis, acne and periodontitis 11. Several antibiotics have been reported to be able, at lower dosages, to have immunomodulatory and anti‐inflammatory actions, suppressing the ‘cytokine storm’ of inflammation and conferring an additional clinical benefit through their immunomodulatory properties 11, 12, 13. NGAL seems to positively modulate the activity of the MMP‐9 enzyme 8, 9, which degrades basement membranes as well as the extracellular matrix, thus liberating vascular endothelial growth factor, which is involved in wound healing 10. ![]() Chronic wounds, that is, venous ulcers, exhibit dysfunctions in extracellular matrix that cannot support healing, and some studies reported that both matrix metalloproteinases (MMPs) and neutrophil gelatinase‐associated lipocalin (NGAL) could play a role in the healing process in patients with chronic venous ulcers 6, 7. Pharmacological treatments, as doxycycline administration, which by means of its immunomodulatory and anti‐inflammatory actions, through the inhibition of MMP, could improve extracellular matrix functioning and represent a possible solution to support wound healing.Ĭhronic venous disorders are widespread in western countries and their main complication, that is, venous leg ulcers, with an overall prevalence ranging up to 2% in the general population, is responsible for important socioeconomic problems 1, 2, 3, 4, 5. In group B, the lower healing rate was related to higher levels of MMP‐9 neutrophil gelatinase‐associated lipocalin and vascular endothelial growth factor, documented in plasma wound fluid and biopsies executed and compared between both groups. Group A showed a higher healing rate compared with group B. Healing was assessed by means of direct ulcer tracing with computerised planimetry. for 3 months, whereas patients of group B received basic treatment only. Patients of group A in addition to the basic treatment, described above, received the administration of oral low doses of doxycycline 20 mg b.i.d. Patients were randomised into two groups of 32 persons in each (groups A and B). All patients were subjected to the most appropriate treatment considering also the patient's wishes (compression therapy followed or not by vein surgery). Sixty‐four patients with venous ulcers were recruited in a 22‐month period. Matrix metalloproteinases ( MMPs) are involved in the alteration of extracellular matrix that could lead to venous ulceration. Venous ulcers are common, with an overall prevalence of up to 2% in the general population of western countries, and have significant socioeconomic impact. ![]()
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