Marco Rainer Kesting

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.

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.

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.

Immunodepletion of high-abundant proteins from acute and chronic wound fluids to elucidate low-abundant regulators in wound healing

BackgroundThe process of wound healing consists of several well distinguishable and finely tuned phases. For most of these phases specific proteins have been characterized, although the underlying mechanisms of regulation are not yet fully understood. It is an open question as to whether deficits in wound healing can be traced back to chronic illnesses such as diabetes mellitus. Previous research efforts in this field focus largely on a restricted set of marker proteins due to the limitations detection by antibodies imposes. For mechanistic purposes the elucidation of differences in acute and chronic wounds can be addressed by a less restricted proteome study. Mass spectrometric (MS) methods, e.g. multi dimensional protein identification technology (MudPIT), are well suitable for this complex theme of interest. The human wound fluid proteome is extremely complex, as is human plasma. Therefore, high-abundant proteins often mask the mass spectrometric detection of lower-abundant ones, which makes a depletion step of such predominant proteins inevitable.FindingsIn this study a commercially available immunodepletion kit was evaluated for the detection of low-abundant proteins from wound fluids. The dynamic range of the entire workflow was significantly increased to 5-6 orders of magnitude, which makes low-abundant regulatory proteins involved in wound healing accessible for MS detection.ConclusionThe depletion of abundant proteins is absolutely necessary in order to analyze highly complex protein mixtures such as wound fluids using mass spectrometry. For this the used immunodepletion kit is a first but important step in order to represent the entire dynamic range of highly complex protein mixtures in the future.

Bronchoscopy screening in primary oral squamous cell carcinoma: a 10-year experience

Squamous cell carcinoma (SCC) in the head and neck is associated with synchronous or metachronous carcinomas of the lung. Preoperative pulmonary screening is advocated and may be done by bronchoscopy, thoracic radiograph, computed tomography (CT), or positron emission tomography (PET) with CT (PET/CT fusion). We evaluated the role of bronchoscopy in patients with primary oral SCC to ascertain the incidence of synchronous malignancies of the lung. We retrospectively reviewed a decades experience of screening by bronchoscopy in 570 pathologically confirmed and previously untreated patients with oral SCC (188 female, 382 male). Univariate and multivariate analyses were done after evaluating the incidence of synchronous lesions and the clinical and histological features of the index tumour. Investigation by bronchoscopy showed disease in 166 patients, and malignancy of the lung in 9 (2%). The Union International contre le Cancer (UICC) stages I and II oral SCC were significantly associated with a synchronous malignancy of the lung (p=0.038). We recommend the use of bronchoscopy even in early tumour stages. Some patients had their treatment altered because of its use, including upstaging, diagnosis of distant and unresectable disease, and investigation of second primary malignancies.