Apoptosis causes lumen formation during angiogenesis in vitro.

The influence of the C1-inhibitor BERINERT® and the protein-free haemodialysate ACTIHAEMYL20%® on the evolution of the depth of scald burns in a porcine model

Standardized deep partial-thickness burns were inflicted on domestic pigs by scalding 30 per cent of the skin surface for 25 s with 75 degrees C hot water. The animals (n = 18; weight 25-35 kg) were divided into three groups: I, control group (n = 6), Ringer's lactate only; II, haemodialysate group (n = 6), Ringer's lactate and a protein-free haemodialysate of calf-blood (ACTIHAEMYL20%; AH) and III, C1-inhibitor group (n = 6), Ringer's lactate and C1-inhibitor (C1-INH; BERINERT). Skin biopsies were taken at defined time points (4, 28, 52 and 76 h) and investigated histologically. Depth of burn was determined morphometrically after coloration with a modified MTT-staining on frozen sections o…

Biomaterial-based approaches and adult stem cells

Prognostic significance of tumor ploidy and histomorphological parameters in adenocarcinoma of Barrett's esophagus.

<i>Background:</i> Despite recent advances in surgical and multidisciplinary treatment, the prognosis for patients with adenocarcinoma of Barrett’s esophagus remains poor. The low prognostic accuracy of even surgical pathologic TNM staging suggests that additonal parameters are necessary in determining the prognosis. <i>Method:</i> In a retrospective analysis of 50 patients who underwent transhiatal or transthoracic esophageal resection due to adenocarcinoma of Barrett’s esophagus, a quantitative DNA analysis using image cytometry was performed in addition to the TNM classification and usual morphological criteria. At the time of DNA analysis the histomorphological p…

Use of a collagen/elastin-membrane for the tissue engineering of dermis.

In an experimental model in rats, xenogeneic membranes consisting of processed native collagen and elastin were grafted to serve as a template for the formation of a neo-dermis, while in vitro-cultured autogeneic keratinocytes were applied on top of this to restore an epidermis. The process of tissue reconstruction and the digestion of the grafted membrane components were analysed by histological and immunohistochemical methods as well as electron microscopy. Approximately 3 weeks post grafting the membranes were completely vascularised and colonized by different types of cells. After 6 weeks, the collagenous fibres of the graft were mostly replaced by newly formed collagenous texture, wher…

Tissue reaction to sealing materials: different view at biocompatibility

Abstract The biodegradability of root canal sealers in areas other than the root canal system is crucial to the overall success rate of endodontic treatment. The aim of the present study was to investigate, the cell and tissue reaction to GuttaFlow and AHPlus, both in vitro and in vivo. For the in vitro experiments the materials were incubated with Human Periodontal Ligament Fibroblasts and cell proliferation and cytotoxicity analyses were performed. Additional fluorescence-microscope stainings were carried out in order to visualize cell growth and morphology. For assessment of the tissue reaction to the materials a subcutaneous implantation model in Wistar rats was employed and the inflamm…

Boron determination in liver tissue by combining quantitative neutron capture radiography (QNCR) and histological analysis for BNCT treatment planning at the TRIGA Mainz.

The typical primary malignancies of the liver are hepatocellular carcinoma and cholangiocarcinoma, whereas colorectal liver metastases are the most frequently occurring secondary tumors. In many cases, only palliative treatment is possible. Boron neutron capture therapy (BNCT) represents a technique that potentially destroys tumor tissue selectively by use of externally induced, locally confined secondary particle irradiation. In 2001 and 2003, BNCT was applied to two patients with colorectal liver metastases in Pavia, Italy. To scrutinize the rationale of BNCT, a clinical pilot study on patients with colorectal liver metastases was carried out at the University of Mainz. The distribution o…

Activation of Muscarinic Receptors by Non-neuronal Acetylcholine

The biological role of acetylcholine and the cholinergic system is revisited based particularly on scientific research early and late in the last century. On the one hand, acetylcholine represents the classical neurotransmitter, whereas on the other hand, acetylcholine and the pivotal components of the cholinergic system (high-affinity choline uptake, choline acetyltransferase and its end product acetylcholine, muscarinic and nicotinic receptors and esterase) are expressed by more or less all mammalian cells, i.e. by the majority of cells not innervated by neurons at all. Moreover, it has been demonstrated that acetylcholine and “cholinergic receptors” are expressed in non-neuronal organism…

Reduced expression of TLR4 is associated with the metastatic status of human colorectal cancer.

Signaling mediating colorectal cancer (CRC) progression is incompletely understood. Previously, we identified lipopolysaccharide (LPS), an endotoxin of ubiquitously existing colonic bacteria, as a pivotal stimulus increasing the metastatic potential of human CRC. Since the ubiquitous colonic bacteria release large amounts of LPS this observation could be of enormous relevance for the progression of CRC. In this study we present data contributing to the elucidation of its mode of action. Since both receptors CD14 and TLR4 act as LPS mediators, we determined their expression in various CRC cell lines and in 115 non-metastatic, lymphogenous-metastatic and haematogenous-metastatic CRC specimens…

Tissue response and biomaterial integration: the efficacy of in vitro methods

Implantation involves tissue trauma, which evokes an inflammatory response, coupled to a wound healing reaction, involving angiogenesis, fibroblast activation and matrix remodelling. Until now the type and extent of such reactions to give optimal integration of various biomaterials are practically unknown. Three principal fields of research can yield useful data to understand these phenomena better: studies on explanted biomaterials, animal models and relevant in vitro techniques. This paper will present examples of the latter field and the application of endothelial cell (EC) culture systems to study the effects of important tissue (e.g. pro-inflammatory cytokines, chemokines) and material…

FVIII production by human lung microvascular endothelial cells

While extrahepatic factor VIII (FVIII) synthesis suffices for hemostasis, the extrahepatic production sites are not well defined. We therefore investigated the ability of the human lungs to produce FVIII. Lungs from heart-beating donors who were declined for transplantation were perfused and ventilated in an isolated reperfusion model for 2 hours. A progressive accumulation of FVIII and von Willebrand factor (VWF) was recorded in the perfusion medium in 3 of 4 experiments. By contrast, factor V, fibrinogen, and immunoglobulin G (IgG) levels remained constant during the perfusion period, indicating that the accumulation of FVIII and VWF was not due to diffusion from the intercellular medium …

The Non-neuronal Cholinergic System

Acetylcholine, one of the most exemplary neurotransmitters, has been detected in bacteria, algae, protozoa, tubellariae and primitive plants, suggesting an extremely early appearance in the evolutionary process and a wide expression in non-neuronal cells. In plants (Urtica dioica), acetylcholine is involved in the regulation of water resorption and photosynthesis. In humans, acetylcholine and/or the synthesizing enzyme, choline acetyltransferase, have been demonstrated in epithelial (airways, alimentary tract, urogenital tract, epidermis), mesothelial (pleura, pericardium), endothelial, muscle and immune cells (granulocytes, lymphocytes, macrophages, mast cells). The widespread expression o…

Metallic nanoparticles exhibit paradoxical effects on oxidative stress and pro-inflammatory response in endothelial cells in vitro

Particulate matter is associated with different human diseases affecting organs such as the respiratory and cardiovascular systems. Very small particles (nanoparticles) have been shown to be rapidly internalized into the body. Since the sites of internalization and the location of the detected particles are often far apart, a distribution via the blood stream must have occurred. Thus, endothelial cells, which line the inner surface of blood vessels, must have had direct contact with the particles. In this study we tested the effects of metallic nanoparticles (Co and Ni) on oxidative stress and proinflammatory response in human endothelial cells in vitro. Exposure to both nanoparticle types…

Fibronectin-mediated endothelialisation of chitosan porous matrices.

Chitosan (Ch) porous matrices were investigated regarding their ability to be colonized by human microvascular endothelial cells (HPMEC-ST1.6R cell line) and macrovascular endothelial cells namely HUVECs. Specifically we assessed if previous incubation of Ch in a fibronectin (FN) solution was effective in promoting endothelial cell (EC) adhesion to Ch matrices with different degrees of acetylation (DAs). Upon FN physiadsorption, marked differences were found between the two DAs investigated, namely DA 4% and 15%. While cell adhesion was impaired on Ch with DA 15%, ECs were able to not only adhere to Ch with DA 4%, but also to spread and colonize the scaffolds, with retention of the EC pheno…

Isolated erythema (cellulitis) of the breast.

Abstract This paper reports nine cases of breast cellulitis in women patients (four cases in pregnancy, four postmenopausal cases following hormone replacement therapy and one case of unilateral breast oedema following a mediastinal lymphoma). Biopsies were obtained from the erythematous area in one pregnant patient, one postmenopausal patient and the patient with breast oedema associated with the mediastinal lymphoma. Histology revealed unspecific dermatitis with extensive perivascular lymphoplasmocellular infiltrates. Histopathological examination of biopsies obtained from the underlying mammary tissue along with the corresponding mammographic data gave no evidence of mastitis or mammary …

Prediction model of lymph node metastasis in superficial esophageal adenocarcinoma and squamous cell cancer including D2-40 immunostaining

Background It was the aim of our study to establish a model for prediction of lymph node metastases in superficial esophageal cancer. Methods We analyzed the clinical and histopathological data of 50 consecutive patients with pT1-esophageal cancer who underwent oncological resection. Submucosal carcinomas (pT1b) were classified according to sm levels 1–3. D2-40 immunostaining was investigated using the ABC technique. In a first step, we performed univariate analysis (One-way ANOVA: Sigma restricted parameterization; test of SS whole vs. SS predicted) to test the predictive value of the following categorical parameters for lymph node status (positive/negative): sex, histologic tumor type, lo…

Focal adhesions and assessment of cytotoxicity

Focal adhesions are highly ordered assemblies of transmembrane receptors, extracellular matrix proteins, and a large number of cytoplasmic proteins, including structural proteins, as well as tyrosine kinases, phosphatases, and their substrates. They are now accepted as a prime component of signal transduction. Because focal adhesions also play an important role in cell morphology and migration, it can be argued that their presence is indicative of healthy cells. This has been the reason for several research groups to conclude that biomaterials sustaining focal adhesion assembly are biocompatible. In this study we demonstrate that cells under cytotoxic stress may still be able to retain thei…

Infected osteoradionecrosis of the mandible: follow-up study suggests deterioration in outcome for patients with Actinomyces-positive bone biopsies.

Abstract Infected osteoradionecrosis (IORN) is one of the major complications of oral cancer radiotherapy. Recent studies showed a high prevalence of Actinomyces in IORN. In this study, the clinical follow up of IORN patients ( n  = 25; 20 male, 5 female) with regard to Actinomyces detection in the mandible was analyzed. Within 1.6–119 months of follow up, disease control was achieved in almost 90% of the patients with Actinomyces -negative bone biopsies, but only in 25% of the Actinomyces -positive group. The presence of Actinomyces was associated with a significantly higher risk of treatment failure ( P  = 0.004; Fisher's exact test). This held true when the data were controlled for ‘exte…