Effects of LL-37 Peptide Mimetics on Gingival Fibroblast Function

Host defence peptides, including the cathelicidin LL-37, play an important role in mucosal immunity, functioning as both antimicrobial agents and modulators of the inflammatory response. In the current climate of antibiotic resistance, the idea of using naturally occurring antimicrobial peptides, or their synthetic mimetics, to combat oral infection is particularly appealing. Objectives: The aim of this study was to investigate the effects of parent LL-37, and two peptide mimetics (KR-12 and KE-18), on cytokine expression and response to bacterial challenge by gingival fibroblasts. Methods: KR-12 and KE-18 are peptide mimetics of the biologically active, mid-region sequence of LL-37. The effects of commercially available LL-37, KR-12 and KE-18 on gingival fibroblast response to E coli and P gingivalis LPS challenge, analysed by IL-6 and IL-8 expression, were determined in cell culture by ELISA. The direct effects of each peptide on IL-6, IL-8, CXCL-1 and HGF expression were also determined by ELISA. The MTT assay was used to evaluate peptide effects on fibroblast viability. Results: LL-37 and KE-18, but not KR-12, inhibited LPS induction of inflammatory cytokine expression and directly stimulated CXCL-1 production by fibroblasts. All 3 peptides stimulated production of IL-8 and HGF. Neither LL-37 nor KE-12 affected cell viability, while KE-18, at higher concentrations, induced cell death. Conclusions: Shorter, peptide mimetics of LL-37, in particular KE-18, retain the immunomodulatory effects of the parent molecule and possess excellent potential as therapeutic agents in the treatment of oral infections including periodontal disease.

Antifungal Activity of LL-37 and Truncated Mimetics

Background: Candida albicans is a commensal organism and a constituent of the normal oral flora. Cell concentrations of 1x102 cells/ml and below are indicative of commensal colonisation in the oral cavity, above this level C. albicans can become an opportunistic pathogen; it is the most prevalent human fungal pathogen and a causal agent of the oral infection, candidiasis. The capacity of C. albicans to cause infection arises from its ability to exist in a biofilm ecosystem. Mature C. albicans biofilms display a high level of resistance to antifungals and the need for other therapeutic options has become paramount. Objectives: The objectives of the current study were to determine the antifungal activity of LL-37 (a member of the human cathelicidin family) and two truncated peptide mimetics against C. albicans in both planktonic and biofilm form. Methods: Radial diffusion assays were used to obtain the minimum inhibitory concentration (MIC) of LL-37 and the truncated mimetics KE-18 and KR-12 against planktonic C. albicans. A 96 well microtitre plate assay was employed to study the effects of the peptides on early candida biofilm formation (up to 24 hours) compared with the antifungal drug fluconazole. Biofilm quantification was achieved using the crystal violet assay. Results: MIC values obtained: LL-37 >250µg/ml; KE-18 51µg/ml; and KR-12 11µg/ml. LL-37 significantly reduced the quantity of biofilm formed by C.albicans at both the 4 h and 24 h timepoints (p <0.0001). KE-18 showed significant biofilm reduction over 4 h and 24 h (p=0.0002, p=0.013 respectively), KR-12 showed significant reduction at the 24 h time point only (p=0.0256). Conclusions: Results suggest that LL-37 has the ability to disrupt early biofilm formation of C. albicans with its potency of action similar with that of fluconazole.

The History of Rome in Painting

There are many paths to reach Rome, immense field open to the eye through the centuries and days, where the presence of the story is haunting. All the artists came to Rome: Italians of various Italian and also French, Dutch, Flemish, Spanish, English and Americans. These painters whose works tell its long history for having lived in the glare of light forever are the Roman pantheon of arts: what are all the anonymous authors of the frescoes of ancient Rome and medieval, but Fabriano, Cimabue , Giotto, Botticelli, Raphael, Giulio Romano, Michelangelo, Caravaggio, Guido Reni, Guercino, Titian, Vasari, Velasquez, Le Nain, Poussin, Zuccari, Van Wittel, Eckersberg, Giraudet, David, Panini, Hubert Robert, Reynolds, Fuseli, Ingres, Sargent, Caffi, Vernet, Turner, Corot, Caffi, De Chirico, etc..

Message from the President of the United States, transmitting copies of a convention concluded at St. Petersburg, the 12th day of July, 1822, under the mediation of the Emperor of all the Russias, between the United States of America and His Britannic Majesty. --

United States. 18th Congress, 1st session, 1823-1824. House. Doc. no. 30.

The fall of Maximilian, late Emperor of Mexico : Whit an historical introduction

UANL

Life of Maximilian I late Emperor of Mexico, with a sketch of the Empress Carlota

UANL

Ahmedabad | Laboratorio di architettura moderna Il National Institute of Design (1961-68) fra contatti internazionali ed echi della tradizione

Oggetto della ricerca è lo studio del National Institute of Design (NID), progettato da Gautam Sarabhai e sua sorella Gira, ad Ahmedabad, assunta a paradigma del nuovo corso della politica che il Primo Ministro Nehru espresse nei primi decenni del governo postcoloniale. Obiettivo della tesi è di analizzare il fenomeno che unisce modernità e tradizione in architettura. La modernità indiana, infatti, nacque e si sviluppò con i caratteri di un Giano bifronte: da un lato, la politica del Primo Ministro Nehru favorì lo sviluppo dell’industria e della scienza; dall’altro, la visione di Gandhi mirava alla riscoperta del locale, delle tradizioni e dell’artigianato. Questi orientamenti influenzarono l’architettura postcoloniale. Negli anni ‘50 e ’60 Ahmedabad divenne la culla dell’architettura moderna indiana. Kanvinde, i Sarabhai, Correa, Doshi, Raje trovarono qui le condizioni per costruire la propria identità come progettisti e come intellettuali. I motori che resero possibile questo fermento furono principalmente due: una committenza di imprenditori illuminati, desiderosi di modernizzare la città; la presenza ad Ahmedabad, a partire dal 1951, dei maestri dell’architettura moderna, tra cui i più noti furono Le Corbusier e Kahn, invitati da quella stessa committenza, per la quale realizzarono edifici di notevole rilevanza. Ad Ahmedabad si confrontarono con forza entrambe le visioni dell’India moderna. Lo sforzo maggiore degli architetti indiani si espresse nel tentativo di conciliare i due aspetti, quelli che derivavano dalle influenze internazionali e quelli che provenivano dallo spirito della tradizione. Il progetto del NID è uno dei migliori esempi di questo esercizio di sintesi. Esso recupera nella composizione spaziale la lezione di Wright, Le Corbusier, Kahn, Eames ibridandola con elementi della tradizione indiana. Nell’uso sapiente della struttura modulare e a padiglione, della griglia ordinatrice a base quadrata, dell’integrazione costante fra spazi aperti, natura e architettura affiorano nell’edificio del NID echi di una cultura millenaria.

Role of glial cells in the functional expression of LL-37/rat cathelin-related antimicrobial peptide in meningitis

Antimicrobial peptides are intrinsic to the innate immune system in many organ systems, but little is known about their expression in the central nervous system. We examined cerebrospinal fluid (CSF) and serum from patients with active bacterial meningitis to assess antimicrobial peptides and possible bactericidal properties of the CSF. We found antimicrobial peptides (human cathelicidin LL-37) in the CSF of patients with bacterial meningitis but not in control CSF. We next characterized the expression, secretion, and bactericidal properties of rat cathelin-related antimicrobial peptide, the homologue of the human LL-37, in rat astrocytes and microglia after incubation with different bacterial components. Using real-time polymerase chain reaction and Western blotting, we determined that supernatants from both astrocytes and microglia incubated with bacterial component supernatants had antimicrobial activity. The expression of rat cathelin-related antimicrobial peptide in rat glial cells involved different signal transduction pathways and was induced by the inflammatory cytokines interleukin 1beta and tumor necrosis factor. In an experimental model of meningitis, infant rats were intracisternally infected with Streptococcus pneumoniae, and rat cathelin-related antimicrobial peptide was localized in glia, choroid plexus, and ependymal cells by immunohistochemistry. Together, these results suggest that cathelicidins produced by glia and other cells play an important part in the innate immune response against pathogens in central nervous system bacterial infections.