Azithromycin possesses biofilm–inhibitory activity and potentiates non-bactericidal colistin methanesulfonate (CMS) and polymyxin B against <i>Klebsiella pneumonia</i>

Novel antibiotic combinations may act synergistically to inhibit the growth of multidrug-resistant bacterial pathogens but predicting which combination will be successful is difficult, and standard antimicrobial susceptibility testing may not identify important physiological differences between planktonic free-swimming and biofilm-protected surface-attached sessile cells. Using a nominally macrolide-resistant model Klebsiella pneumoniae strain (ATCC 10031) we demonstrate the effectiveness of several macrolides in inhibiting biofilm growth in multi-well plates, and the ability of azithromycin (AZM) to improve the effectiveness of the antibacterial last-agent-of-choice for K. pneumoniae infections, colistin methanesulfonate (CMS), against biofilms. This synergistic action was also seen in biofilm tests of several K. pneumoniae hospital isolates and could also be identified in polymyxin B disc-diffusion assays on azithromycin plates. Our work highlights the complexity of antimicrobial-resistance in bacterial pathogens and the need to test antibiotics with biofilm models where potential synergies might provide new therapeutic opportunities not seen in liquid culture or colony-based assays

Potent Inhibition of Cicatricial Contraction in Proliferative Vitreoretinal Diseases by Statins

OBJECTIVE—Despite tremendous progress in vitreoretinal surgery, certain postsurgical complications limit the success in the treatment of proliferative vitreoretinal diseases (PVDs), such as proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). One of the most significant complications is the cicatricial contraction of proliferative membranes, resulting in tractional retinal detachment and severe vision loss. Novel pharmaceutical approaches are thus urgently needed for the management of these vision-threatening diseases. In the current study, we investigated the inhibitory effects of statins on the progression of PVDs

A selective cyclic integrin antagonist blocks the integrin receptors α(v)β(3 )and α(v)β(5 )and inhibits retinal pigment epithelium cell attachment, migration and invasion

BACKGROUND: Proliferative vitreoretinopathy (PVR) is a leading cause of blindness after failed retinal reattachment surgery. PVR is characterized by the proliferation, migration and contraction of retinal pigmented epithelial cells (RPE), and these cellular responses are influenced by the expression and function of integrin receptors. The effect of a cyclic integrin antagonist containing the amino acid sequence Arg-Gly-Asp-D-Phe-Val (RGDfV), specific for the integrin receptors α(v)β(3 )and α(v)β(5), was investigated on basic fibroblast growth factor (bFGF), platelet derived growth factor-BB (PDGF-BB), and serum induced human RPE proliferation, migration, invasion and attachment to the extracellular matrix. Furthermore, the effects of bFGF and PDGF-BB regulated expression of integrins α(v)β(3 )and α(v)β(5 )on RPE cells was examined. METHODS: The effect of a cyclic integrin antagonist and a control peptide (0.01 μg/ml to 300 μg/ml) was investigated on serum or cytokine (bFGF or PDGF-BB pretreatment) induced human fetal RPE cell proliferation by H(3)-thymidine uptake. The effect of the cyclic integrin antagonist on RPE cell attachment onto different extracellular matrices (laminin, collagen IV, fibronectin), RPE cell invasion stimulated by PDGF-BB or serum, and migration stimulated by PDGF-BB, vascular endothelial growth factor (VEGF) or serum was explored. PDGF-BB and bFGF modulation of the integrin receptors α(v)β(3 )and α(v)β(5 )was evaluated by flow cytometry. RESULTS: The integrin antagonist did not inhibit DNA synthesis stimulated by serum, bFGF, or PDGF-BB treatment. RPE attachment onto fibronectin was inhibited in a concentration range of 1–10 μg/ml (p < 0.05). Attachment of the RPE cells onto collagen IV and laminin was inhibited in a range of 3–10 μg/ml (p < 0.05). Serum and PDGF-BB stimulated migration was inhibited by the cyclic integrin antagonist in a concentration range of 1–10 μg/ml (p < 0.05). Furthermore, the cyclic integrin antagonist inhibited PDGF-BB stimulated RPE cell invasion through fibronectin (3μg/ml: 66% inhibition, p < 0.001). In each of these experiments, the control peptides had no significant effects. PDGF-BB and bFGF pretreatment of RPE cells increased the expression of integrin receptors α(v)β(3 )(bFGF: 1.9 fold, PDGF-BB: 2.3 fold) and α(v)β(5 )(bFGF: 2.9 fold, PDGF-BB: 1.5 fold). CONCLUSION: A selective inhibition of the integrin receptors α(v)β(3 )and α(v)β(5 )through a cyclic integrin antagonist is able to inhibit RPE cell attachment, migration and invasion. Since these steps are of importance for the progression of PVR, a cyclic integrin antagonist should be further evaluated for the treatment of this disease

Dermatoscopic patterns observed in acral nevi among 3 ethnic groups

Acral pigmented lesions have unique patterns of dermatoscopic features due to the skin anatomy in this region. We performed a pilot study documenting common dermatoscopic patterns of clinically benign acral nevi in white (W), Hispanic (H), and African-Americans (AA). This study was approved by the UIC institutional review board. We examined 141 consecutive patients who presented to the UIC dermatology clinic and volunteered to participate. Images were captured using a digital polarized dermatoscopy photography system. All images were reviewed by 2 investigators. Unclear images and those from transitional zones were not included in the review for a total of 106 lesions, 65 palmar melanocytic nevi, and 41 plantar melanocytic nevi. The largest group of hand (palm) nevi photographs were from AAs (39 total) had the following distribution of patterns: a) 26 parallel furrow pattern (PFP); b) 6 nontypical; c) 3 lattice-like; d) 1 fibrillar; e) 1 globulostreak; f) 1 globular; and g) 1 homogenous. A smaller number of images were available from H (12) andW (14) groups. Palmar patterns from Hs were a) 11 PFP and b) 1 globular pattern while among whites a) 11 PFP; b) 2 nontypical; and c) 1 homogenous pattern were observed. A total of 41 foot (plantar) melanocytic nevi were photographed. Among the AA group (16 images) there were a) 7 PFP; b) 3 nontypical; c) 2 lattice-like; d) 2 PFP with lattice-like; e) 1 fibrillar; and f) 1 bluish homogenous. Among H (10) with plantar nevi there were 9 PFP patterns and 1 bluish homogenous while among theW (15) volunteers 14 had PFP and 1 nontypical pattern. Benign melanocytic acral dermatoscopic patterns include PFP, lattice-like, fibrillar, homogenous, globulostreak- like, reticular, globular, and nontypical. Nontypical patterns do not have a pattern they can be classified into and are not suggestive of malignancy either clinically or dermatoscopically. The PFP was the most common pattern observed in all ethnicities (78/74%) in following proportions: hands 1) AA 26/66%; 2) H 11/92%; W 11/78%; for the lesions on the feet 4) AA 7/44%; 5) H 9/90%; and 6) W 14/93%. PFP with linear pigmentation was themost common variant while double-dotted the least. AAs had the largest variety of patterns while Hispanic and Caucasian lesions were more likely to show a parallel furrow pattern. AAs were also more likely to have the lattice-like and nontypical patterns on hands or feet. Larger studies can help further clarify ethnic variations in acral nevi

Woman and love,

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