Epigallocatechin-gallate (EGCg), the major catechin present in green tea extracts, has been shown to have several antibacterial activities, limiting bacterial growth and invasion and acting in synergy with ␤-lactam antibiotics. In this article, we report that EGCg at doses half and below its calculated MIC of 100 g/ml, is able to reverse tetracycline resistance in staphylococcal isolates expressing the specific efflux pump Tet(K) and appears to improve the MICs of tetracycline for susceptible staphylococcal isolates as well. The visible effect of EGCg is an increased accumulation of tetracycline inside bacterial cells. This effect is likely due to the inhibition of pump activity, and it is evident not only for Tet(K) pumps but also for efflux pumps of a different class [Tet(B)]. In summary, our data indicate that the observed dramatic enhancement by EGCg of tetracycline activity for resistant staphylococcal isolates is caused by impairment of tetracycline efflux pump activity and increased intracellular retention of the drug, suggesting a possible use of EGCg as an adjuvant in antibacterial therapy.

Autophagy is an important homeostatic cellular process encompassing a number of consecutive steps indispensable for degrading and recycling cytoplasmic materials. Basically autophagy is an adaptive response that under stressful conditions guarantees the physiological turnover of senescent and impaired organelles and, thus, controls cell fate by various cross-talk signals. Diabetic retinopathy (DR) is a serious microvascular complication of diabetes and accounts for 5% of all blindness. Although, various metabolic disorders have been linked with the onset of DR, due to the complex character of this multi-factorial disease, a connection between any particular defect and DR becomes speculative. Diabetes increases inflammation, advanced glycation end products (AGEs) and oxidative stress in the retina and its capillary cells. Particularly, a great number of evidences suggest a mutual connection between oxidative stress and other major metabolic abnormalities implicated in the development of DR. In addition, the intricate networks between autophagy and apoptosis establish the degree of cellular apoptosis and the progression of DR. Growing data underline the crucial role of reactive oxygen species (ROS) in the activation of autophagy. Depending on their delicate balance both redox signaling and autophagy, being detrimental or beneficial, retain opposing effects. The molecular mechanisms of autophagy are very complex and involve many signaling pathways cooperating at various steps. This review summarizes recent advances of the possible molecular mechanisms in autophagic process that are involved in pathophysiology of DR. In-depth analysis on the molecular mechanisms leading to autophagy in the retinal pigment epithelial (RPE) will be helpful to plan new therapies aimed at preventing or improving the progression of DR.

Epigallocatechin gallate (EGCg), the main polyphenol component of green tea, has several antibacterial properties. Here we show that sub-MICs of EGCg appear to decrease slime production, therefore inhibiting biofilm formation by ocular staphylococcal isolates previously characterized for the presence of ica genes by the Congo red agar plate assay and for adhesion to microtiter plates.Biofilm formation is a three-stage process (6) that significantly contributes to the pathogenesis of staphylococcal infections. The first stage, docking, is mainly due to hydrophobic interactions, whereas the next two stages, locking and maturation, are mediated by capsular polysaccharide adhesins, PIA (polysaccharide intercellular adhesin) and PNAG (poly-Nacetylglucosamine polysaccharide), both of which are synthesized by the gene products of the ica operon (icaADBC), with the main contribution coming from an N-acetylglucosaminyltransferase encoded by the icaA gene (5, 12). The expression of the icaA gene alone results in low enzymatic activity, but coexpression with icaD leads to a significant increase in activity (8).Green tea polyphenols and, more specifically, epigallocatechin gallate (EGCg) are known to possess both direct bactericidal activity (18,19) and the ability to potentiate the effects of certain antibiotics (15,16,17,21). Moreover, they have already been shown to have at least an indirect influence on biofilm production, in that they can retard the formation of dental plaque (9,11,20).In this study, we have investigated the effects of sub-MICs of EGCg (99% pure; Sigma) ( Fig. 1A, inset) on biofilm formation by 20 different ocular staphylococcal isolates derived from patients with community-acquired ocular infections and belonging to our private collection. The different isolates included 8 Staphylococcus aureus isolates and 12 Staphylococcus epidermidis isolates. Moreover, two American Type Culture Collection strains (S. epidermidis ATCC 35984 and S. epidermidis ATCC 12228) were used as reference controls. Table 1 summarizes the characterization of bacterial isolates for biofilm production. The MIC of EGCg for each strain was determined in tryptic soy broth (TSB) by a broth dilution method according to the guidelines of the CLSI (formerly the NCCLS) (13). The quality of the lot of EGCg was controlled by reverse-phase high-pressure liquid chromatography (HPLC) and showed just one single, sharp peak, suggesting a very high degree of purity (Fig. 1A). The MICs obtained ranged from 125 to 500 mg/ml, similar to that which we reported recently (17); however, they were slightly higher than those already described by other authors (22, 24).Each ocular isolate was then characterized for biofilm-related properties. Biofilm-forming ability was tested by determination of adhesion to microtiter plates (5) and was quantitated by safranin staining and reading of the absorbance at 492 nm. The biofilm production of the different strains was then arbitrarily classified as strong (optical density [OD], Ͼ0.9 OD), medium (0.6 Ͻ OD Ͻ 0.9),...

UPARANT mitigates laser-induced CNV by inhibiting angiogenesis and inflammation through an action on transcription factors encoding angiogenesis and inflammatory genes. The finding that UPARANT is effective against CNV may help to establish uPAR and its membrane partners as putative targets in the treatment of AMD.

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