Sammy Al-Benna

Host defense peptides and their antimicrobial-immunomodulatory duality.

Host defence peptides (HDPs) are short cationic molecules produced by the immune systems of most multicellular organisms and play a central role as effector molecules of innate immunity. Host defence peptides have a wide range of biological activities from direct killing of invading pathogens to modulation of immunity and other biological responses of the host. HDPs have important functions in multiple, clinically relevant disease processes and their imbalanced expression is associated with pathology in different organ systems and cell types. Furthermore, HDPs are now evaluated as model molecules for the development of novel natural antibiotics and immunoregulatory compounds. This review provides an overview of HDPs focused on their antimicrobial-immunomodulatory duality.

Oncolytic activities of host defense peptides.

Cancer continues to be a leading source of morbidity and mortality worldwide in spite of progress in oncolytic therapies. In addition, the incidence of cancers affecting the breast, kidney, prostate and skin among others continue to rise. Chemotherapeutic drugs are widely used in cancer treatment but have the serious drawback of nonspecific toxicity because these agents target any rapidly dividing cell without discriminating between healthy and malignant cells. In addition, many neoplasms eventually become resistant to conventional chemotherapy due to selection for multidrug-resistant variants. The limitations associated with existing chemotherapeutic drugs have stimulated the search for new oncolytic therapies. Host defense peptides (HDPs) may represent a novel family of oncolytic agents that can avoid the shortcomings of conventional chemotherapy because they exhibit selective cytotoxicity against a broad spectrum of malignant human cells, including multi-drug-resistant neoplastic cells. Oncolytic activity by HDPs is usually via necrosis due to cell membrane lysis, but some HDPs can trigger apoptosis in cancer cells via mitochondrial membrane disruption. In addition, certain HDPs are anti-angiogenic which may inhibit cancer progression. This paper reviews oncolytic HDP studies in order to address the suitability of selected HDPs as oncolytic therapies.

Host Defense Peptides as Effector Molecules of the Innate Immune Response: A Sledgehammer for Drug Resistance?

Host defense peptides can modulate the innate immune response and boost infection-resolving immunity, while dampening potentially harmful pro-inflammatory (septic) responses. Both antimicrobial and/or immunomodulatory activities are an integral part of the process of innate immunity, which itself has many of the hallmarks of successful anti-infective therapies, namely rapid action and broad-spectrum antimicrobial activities. This gives these peptides the potential to become an entirely new therapeutic approach against bacterial infections. This review details the role and activities of these peptides, and examines their applicability as development candidates for use against bacterial infections.

Psoriasin (S100A7) up-regulation in oral squamous cell carcinoma and its relation to clinicopathologic features

Proteomic analysis recently suggested aberrant psoriasin (S100A7) expression in oral squamous cell carcinoma (OSCC). In this study, OSCC specimens and matching normal oral tissues from 45 patients who had undergone ablative surgery were examined. Increased psoriasin expression at mRNA level was observed in OSCC samples by quantitative real-time RT-PCR (p=0.015). Immunofluorescence analysis with psoriasin antibody confirmed these observations. Moreover, significantly increased mRNA ratios between malignant and normal samples were correlated with early UICC stage (p=0.006), T1/T2 tumour classification (p=0.043), absence of cervical lymph node metastasis (p=0.027) and age under 65 (p=0.009). Additionally, well-differentiated tumour tissues demonstrated a significantly higher psoriasin expression than moderate and poor differentiated carcinomas (p=0.018). Based on this data, we conclude that psoriasin is a positive marker for oral cancerogenesis and early tumour progression.

Evaluation of toxic side effects of clinically used skin antiseptics in vitro.

BACKGROUND Skin antiseptics are widely used in health-care worldwide. However, there is a need to determine cytotoxicity of these medications on wounds. The aim of this study was to evaluate cytotoxic effects of five clinically used antiseptics on human skin cells. MATERIAL AND METHODS Five clinically used skin antiseptics (Prontosan, Lavasept, Braunol, Octenisept, and Betaisodona) were tested. The minimal inhibitory concentration was determined against Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Escherichia coli). The cytotoxic effects on primary keratinocytes, fibroblasts, and a HaCaT cell line were determined (MTT-assay and BrdU-ELISA) at a wide range of concentrations. RESULTS The agents tested showed effective antibacterial properties (Octenisept, Lavasept, and Prontosan showed higher efficacy than Braunol and Betaisodona) and different degrees of cytotoxicity. Lavasept and Prontosan demonstrated less toxicity on primary human fibroblasts and keratinocytes, whereas Octenisept, Betaisodona, and Braunol showed a significant (P<0.05) decrease in cell viability to 0% on keratinocytes at concentrations of 4%, 7.5%, and 12.5%, and on fibroblasts at 7.5% and 10%, respectively. CONCLUSION Due to the cytotoxic effect of some antiseptics on human skin cells, it is advised that health care professionals balance the cytotoxicity of the medication, their antiseptic properties, and the severity of colonization when selecting a wound care antiseptic. In this study, Lavasept and Prontosan showed best result regarding antibacterial efficacy and cell toxicity.

Revascularization and tissue regeneration of an empty root canal space is enhanced by a direct blood supply and stem cells.

BACKGROUND Regenerative endodontics is an innovative treatment concept aiming to regenerate pulp, dentin and root structures. In the diseased or necrotic tooth, the limitation in vascular supply renders successful tissue regeneration/generation in a whole tooth challenging. The aim of this study is to evaluate the ability of vascularized tissue to develop within a pulpless tooth using tissue engineering techniques. MATERIALS AND METHODS A pulpless tooth chamber, filled with collagen I gel containing isolated rat dental pulp cells (DPC) and angiogenic growth factors, was placed into a hole created in the femoral cortex or into its own tooth socket, respectively. The gross, histological and biochemical characteristics of the de novo tissue were evaluated at 4 and 8 weeks post-transplantation. RESULTS Tooth revascularization and tissue generation was observed only in the femur group, confirming the important role of vascular supply in tissue regeneration. The addition of cells and growth factors significantly promoted connective tissue production in the tooth chamber. CONCLUSION Successful revascularization and tissue regeneration in this model demonstrate the importance of a direct vascular supply and the advantages of a stem cell approach.

Accuracy of references in burns journals

AIMS To study the incidence and risk factors for citation and quotation errors in two major burns surgery journals. METHODS 120 references were randomly selected from original articles published in the following two journals - January to December 2006 issues of Burns and Journal of Burn Care & Research. For each reference, the ease of retrieval on PubMed and the presence of citation errors were noted. Two independent observers analysed each reference for quotation errors. The characteristics of the root article, that is, type of study, author numbers, number of references and article word count were noted. RESULTS Of the 120 selected references, 117 referred to articles from indexed medical journals published in English. Among these, 4 articles could not be retrieved due to fatal citation errors (3.3%). A further 12 citation errors were noted giving a total citation error rate of 13.3% (95% CI: 6.74-19.93%). Of the 117 references analysed, the quotation error rate was 13.7% (95% CI: 8.6-19.5%) half of which were major errors. There was no significant association between the combined error rate per article and the journal (Kruskal-Wallis test; p=0.861, type of study (Kruskal-Wallis test; p=0.717), author numbers (Spearmans rho=0.197, p=0.423), article length (Spearmans rho=0.118, p=0.705) or references per article (Spearmans rho=0.229, p=0.189). CONCLUSION Significant numbers of citation and quotation errors still appear in current burns literature. Incorrect spelling of author names and partial omissions of article titles were the two most common errors. No observable underlying factors were identified in this study. The present results serve as a reminder to authors, editors and peer reviewers for more care of citation accuracy when striving for their common goal of scientific excellence.

Revascularization and tissue regeneration of an empty root canal space is enhanced by a direct blood supply and stem cells

BACKGROUND Regenerative endodontics is an innovative treatment concept aiming to regenerate pulp, dentin and root structures. In the diseased or necrotic tooth, the limitation in vascular supply renders successful tissue regeneration/generation in a whole tooth challenging. The aim of this study is to evaluate the ability of vascularized tissue to develop within a pulpless tooth using tissue engineering techniques. MATERIALS AND METHODS A pulpless tooth chamber, filled with collagen I gel containing isolated rat dental pulp cells (DPC) and angiogenic growth factors, was placed into a hole created in the femoral cortex or into its own tooth socket, respectively. The gross, histological and biochemical characteristics of the de novo tissue were evaluated at 4 and 8 weeks post-transplantation. RESULTS Tooth revascularization and tissue generation was observed only in the femur group, confirming the important role of vascular supply in tissue regeneration. The addition of cells and growth factors significantly promoted connective tissue production in the tooth chamber. CONCLUSION Successful revascularization and tissue regeneration in this model demonstrate the importance of a direct vascular supply and the advantages of a stem cell approach.

Suppression of Soft Tissue Sarcoma Growth by a Host Defense-Like Lytic Peptide

Background Soft tissue sarcoma (STS) is an anatomically and histologically heterogeneous neoplasia that shares a putative mesenchymal cell origin. The treatment with common chemotherapeutics is still unsatisfying because of association with poor response rates. Although evidence is accumulating for potent oncolytic activity of host defense peptides (HDPs), their potential therapeutic use is often limited by poor bioavailability and inactivation in serum. Therefore, we tested the designer host defense-like lytic D,L-amino acid peptide [D]-K3H3L9 on two STS cell lines in vitro and also in an athymic and syngeneic mouse model. In recent studies the peptide could show selectivity against prostate carcinoma cells and also an active state in serum. Methods In vitro the human synovial sarcoma cell line SW982, the murine fibrosarcoma cell line BFS-1 and primary human fibroblasts as a control were exposed to [D]-K3H3L9, a 15mer D,L-amino acid designer HDP. Cell vitality in physiological and acidic conditions (MTT-assay), cell growth (BrdU) and DNA-fragmentation (TUNEL) were investigated. Membrane damage at different time points could be analyzed with LDH assay. An antibody against the tested peptide and recordings using scanning electron microscopy could give an inside in the mode of action. In vivo [D]-K3H3L9 was administered intratumorally in an athymic and syngeneic (immunocompetent) mouse model with SW982 and BFS-1 cells, respectively. After three weeks tumor sections were histologically analyzed. Results The peptide exerts rapid and high significant cytotoxicity and antiproliferating activity against the malignant cell lines, apparently via a membrane disrupting mode of action. The local intratumoral administration of [D]-K3H3L9 in the athymic and syngeneic mice models significantly inhibited tumor progression. The histological analyses of the tumor sections revealed a significant antiproliferative, antiangiogenic activity of the treatment group. Conclusion These findings demonstrate the in vitro and in vivo oncolytic activity of [D]-K3H3L9 in athymic and syngeneic mouse models.

Repair of oronasal fistulas with human amniotic membrane in minipigs

We evaluated the use of multilayer human amniotic membrane (HAM) as a grafting material for the repair of mid-palate oronasal fistulas in seven Berlin minipigs. After two weeks, three animals had the fistulas repaired with multilayered HAM grafts, three had them repaired with a collagen-based dermal substitute (INTEGRA((R)), Integra Life Sciences, Plainsboro, NJ, USA), and one fistula was left untreated to serve as a control. Grafts were interposed between the oral and nasal mucosa, traversing the fistulas. After healing for 40 days, the pigs were killed for clinical, histological, and immunohistochemical examination. Two of the three fistulas closed with HAM were successful, the diameter of the third was reduced in size, and there was no change in the diameter of the fistula in the control. This study shows successful closure of oronasal fistulas in minipigs using interposed grafts of cryopreserved HAM, and offers promise as a simple and effective technique for tension-free closure of such fistulas.