In vivo models of primary brain tumors: pitfalls and perspectives

Animal modeling for primary brain tumors has undergone constant development over the last 60 years, and significant improvements have been made recently with the establishment of highly invasive glioblastoma models. In this review we discuss the advantages and pitfalls of model development, focusing on chemically induced models, various xenogeneic grafts of human cell lines, including stem cell-like cell lines and biopsy spheroids. We then discuss the development of numerous genetically engineered models available to study mechanisms of tumor initiation and progression. At present it is clear that none of the current animal models fully reflects human gliomas. Yet, the various model systems have provided important insight into specific mechanisms of tumor development. In particular, it is anticipated that a combined comprehensive knowledge of the various models currently available will provide important new knowledge on target identification and the validation and development of new therapeutic strategies.     

Functional Impressions in Complete Denture and Overdenture Treatment

Tooth loss can cause loss of occlusal, masticatory, esthetic, physiognomic, phonetic and psychosocial function of patients. The most frequently used treatment method of completely edentulous patients and patients with a small number of remaining teeth are complete dentures or overdentures. One of the most important clinical and laboratory procedures in their fabrication is functional impression taking. The aim of this paper was to present procedures of taking functional impressions in fabrication of complete dentures and overdentures, using standardized techniques and materials. An accurate functional impression together with other correctly performed clinical and laboratory procedures ensure good retention and stability of dentures, which is a precondition for restoring patients’ lost functions.Key words: complete denture, overdenture, functional impression     

Association of epilepsy and headache from the patient perspective

Headache occurs more frequently in patients with epilepsy as compared to the general population. Current studies in patients with epilepsy and migraine show that this increased frequency is independent of the seizure type, etiology or age at onset. People with epilepsy are 2.4 times more likely to be diagnosed with migraine. In our study, we evaluated patients' attitudes toward comorbidity of epilepsy and all headache types. Study results showed a significant number of patients to have experienced headaches after being diagnosed with epilepsy, and some of them assumed it was a side effect of their antiepileptic drug. Based on these data, we propose a more detailed assessment of the history of epilepsy including questions on headache, and offer the epilepsy patient a newer antiepileptic drug. In this way, we can significantly decrease the comorbidity of these two neurologic disorders and improve the quality of life in epilepsy patients.     

Visualization of basal cell carcinoma by fluorescence diagnosis and independent component analysis

Photodynamic detection (PDD) of skin tumours is based on the visualization of a fluorophores, with the ability to accumulate in tumour tissue, by the use of fluorescence imaging. Of particular importance is the application of δ-5-aminolaevulinic acid (ALA) that, through the process of biosynthesis causes formation of the protoporphyrin IX (PpIX). The PpIX has the ability of selective fluorescence after basal cell carcinoma (BCC) has been treated with ALA. Higher concentration of PpIX in tumour tissue compared to surrounding normal skin is the basis for PDD. Our contribution in this preliminary study is application of the independent component analysis (ICA) to extract the BCC spatial map, by processing fluorescent RGB image acquired under excitation with 405 nm light. Comparative performance analysis with other two widely used image processing methods: ratio imaging and optimal threshold based imaging, reveals that ICA produces BCC spatial map that is most consistent in term of diagnostic quality by both visual assessment and calculation of the BCC demarcation line. We believe this represents a solid basis for the design of a compact and low-cost multi-spectral fluorescence imaging system, capable for real time calculation of the skin tumour demarcation.     

An essential role for tumor necrosis factor in the formation of experimental murine Staphylococcus aureus-induced brain abscess and clearance

Tumor necrosis factor-alpha (TNF-alpha) is a central mediator of the immune response to pathogens, but may also exert neurotoxic effects, thereby contributing to immunopathology. To define the role of TNF during the course of brain abscess, TNF-deficient (TNF(0/0) mice were stereotaxically infected with Staphylococcus (S.) aureus-laden agarose beads. In comparison to 100% survival of wild type (WT) mice, TNF(0/0) mice displayed high mortality rates (54%) in the initial phase of abscess development as well as significantly increased morbidity in the course of the disease. The worse clinical outcome was due to an increased intracerebral (i.c.) bacterial load in TNF(0/0) mice as compared to WT mice. The impaired control of S. aureus was associated with reduced inductible nitric oxide synthase (iNOS) mRNA and protein expression in TNF(0/0)mice. Similarly, numbers of inflammatory leukocytes, cytokine expression of IL-6, IL-12p40, IFNgamma IL-beta mRNA, and brain edema were significantly increased in TNF(0/0)mice as compared to WT animals. In addition, resolution of i.c. infiltrates was delayed in TNF(0/0)mice correlating with reduced apoptosis of inflammatory leukocytes and formation of a fibrous abscess capsule. Collectively, these data demonstrate that TNF is of key importance for the control of S. aureus-induced brain abscess and regulates the ensuing host immune response.     

Severe argatroban-induced coagulopathy in a patient with a history of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia is a serious complication of heparin therapy, and it remains a therapeutic challenge in the subset of patients requiring cardiopulmonary bypass. Alternative anticoagulation strategies include lepirudin, danaparoid, bivalirudin, and argatroban, or a combination of unfractionated heparin with a platelet antagonist. Argatroban is eliminated by a hepatic route, making it a practical option for patients with renal insufficiency. However, the lack of an effective antidote poses a significant problem. We present a patient with a history of heparin-induced thrombocytopenia with thrombosis who underwent a redo aortic valve replacement. Although the level of anticoagulation achieved with argatroban was initially adequate, its persistence after the completion of cardiopulmonary bypass proved to be life threatening.