Tatjana Kanjevac

Cytotoxic Effects of Glass Ionomer Cements on Human Dental Pulp Stem Cells Correlate with Fluoride Release

OBJECTIVES Glass ionomer cements (GICs) are commonly used as restorative materials. Responses to GICs differ among cell types and it is therefore of importance to thoroughly investigate the influence of these restorative materials on pulp stem cells that are potential source for dental tissue regeneration. Eight biomaterials were tested: Fuji I, Fuji II, Fuji VIII, Fuji IX, Fuji Plus, Fuji Triage, Vitrebond and Composit. We compared their cytotoxic activity on human dental pulp stem cells (DPSC) and correlated this activity with the content of Fluoride, Aluminium and Strontium ions in their eluates. METHODS Elution samples of biomaterials were prepared in sterile tissue culture medium and the medium was tested for toxicity by an assay of cell survival/proliferation (MTT test) and apoptosis (Annexin V FITC Detection Kit). Concentrations of Fluoride, Aluminium and Strontium ions were tested by appropriate methods in the same eluates. RESULTS Cell survival ranged between 79.62% (Fuji Triage) to 1.5% (Fuji Plus) and most dead DPSCs were in the stage of late apoptosis. Fluoride release correlated with cytotoxicity of GICs, while Aluminium and Strontium ions, present in significant amount in eluates of tested GICs did not. SIGNIFICANCE Fuji Plus, Vitrebond and Fuji VIII, which released fluoride in higher quantities than other GICs, were highly toxic to human DPSCs. Opposite, low levels of released fluoride correlated to low cytotoxic effect of Composit, Fuji I and Fuji Triage.

The New and Old Europe: East-West Split in Pharmaceutical Spending

HIGHLIGHTS Since the geopolitical developments of 1989, former centrally planned economies of Eastern Europe followed distinctively different pathways in national pharmaceutical expenditure evolution as compared to their free market Western European counterparts. Long term spending on pharmaceuticals expressed as percentage of total health expenditure was falling in free market economies as of 1989. Back in early 1990s it was at higher levels in transitional Eastern European countries and actually continued to grow further. Public financing share of total pharmaceutical expenditure was steadily falling in most Central and Eastern European countries over the recent few decades. Opposed scenario were EU-15 countries which successfully increased their public funding of prescription medicines for the sake of their citizens. Pace of annual increase in per capita spending on medicines in PPP terms, was at least 20% faster in Eastern Europe compared to their Western counterparts. During the same years, CEE region was expanding their pharmaceuticals share of health spending in eight fold faster annual rate compared to the EU 15. Private and out-of-pocket expenditure became dominant in former socialist countries. Affordability issues coupled with growing income inequality in transitional economies will present a serious challenge to equitable provision and sustainable financing of pharmaceuticals in the long run.

The relationship between the immune system and oral manifestations of inflammatory bowel disease: a review

Inflammatory bowel diseases (IBDs) are chronic, relapsing inflammatory diseases characterized by exacerbations and remissions of the gastrointestinal tract, clinically manifested as Crohn’s disease and ulcerative colitis. The etiology of IBDs is considered to be multi factorial, comprising environmental, immune, microbial and genetic factors. Clinical signs may include abdominal pain, frequent bloody diarrheas, mucorrhea, vomiting, fever, fatigue or weight loss. Changes in the oral cavity often precede intestinal symptoms. Inflammatory bowel disease leads to a significant deterioration of oral health, which indicates that cooperation between the dentist and the gastroenterologist is necessary when considering patients’ welfare. Patients with IBD have an altered immune response, but microorganisms of the oral cavity may also be responsible for its modification. This review paper discusses the correlation between the immune system and inflammatory bowel disease manifestations in the oral cavity.

Long Term Dental Work Force Build-Up and DMFT-12 Improvement in the European Region.

As Mikiko Hayashi noticed in an amazingly poetic way, dentistry remains in majority of national health systems across the globe: “the Cinderella of health care.” Regardless of undisputed progress of scientific knowledge there is a growing gap in service utilization patterns among the worlds rich and poor citizens. The first tend to consume much of a rather cosmetic expensive treatments without essential health added value. At the same time almost three billion of people belonging to the low income households, lack access to basic dental services or do not pay a visit to a dentist for years (Hayashi et al., 2014). Although the issue of affordability is high at stakes in these countries, uneven distribution between rural and urban areas adds to the challenge. Prime example is definitely India whose giant population was served by 117,825 registered dentists out of whom almost 90,000 were concentrated in only four out of thirty Indian federal states (Vundavalli, 2014). Another case is Australia with its huge geographic area and recently reported ratio of almost 40,000% differential between dentist density in the suburbs of core coastline cities and desert Aboriginal communities (Tennant et al., 2013). Due to international efforts addressing global oral health deficiencies national capacities worldwide have increased sharply over past few decades (Petersen, 2003). Important part of this capacity build-up was grounds laid down by establishment of “WHO Oral Health Country/Area Profile Programme” (or “CAPP”) by the World Health Organization (WHO) back in 1990s. Its cause was the fact that evidence based policy needed reliable and internationally comparable field data. The two main WHO Collaborating Centers whom we own existence and maintenance of these public registries are the Niigata University, Japan and Faculty of Odontology, Malmo, Sweden. The first is in charge of Periodontal Country Profiles and the latter pursues the uneasy task of providing broader Country Oral Health Profiles. Nevertheless other comprehensive sources of evidence on oral health status across regions and nations developed independently. FDI World Dental Federation provides access to the its own Data Hub which consists of fusioned national data sources originating from WHO and World Bank (WB) and Globocan official registries. The European Health for All database (HFA-DB) created and updated by the WHO Office for the European Region and refers to a total of 53 countries located in the European continent. Some of the aforementioned investments allowed for revelation of hidden long term national patterns in oral health care and identification of core weaknesses that might serve as appropriate policy targets in future. So far there is scarcity of published evidence comparing efficiency of all European countries in dental workforce build-up and its relationship to the dental health status of school children in a several decades long time horizon.

ST2 deletion increases inflammatory bone destruction in experimentally induced periapical lesions in mice.

INTRODUCTION ST2 is a member of the interleukin (IL)-1 receptor family, and IL-33 is its natural ligand. ST2 signaling promotes Th2 immune response in allergy, autoimmunity, and chronic inflammatory disorders, but its role in the pathogenesis of periapical lesions is unknown. The purpose of this study was to investigate whether ST2 gene deletion affects the development of experimentally induced periapical lesions in mice. METHODS Pulps of mandibular molars from wild-type (WT) and ST2 knockout (ST2(-)/(-)) BALB/c mice were exposed and left open to the oral environment. After death, hemi-mandibles were isolated and prepared for histologic, immunohistochemical, and flow cytometric analysis. RESULTS The expression of IL-33 and its receptor ST2 was higher in periapical lesions in WT mice compared with normal root apices (both P < .05). The increased periapical bone loss observed in ST2(-)/(-) mice was associated with enhanced influx of neutrophils, CD3+ CXCR3+ Th1 cells, and CD3+ CCR6+ Th17 cells and increased number of tartrate-resistant acid phosphatase+ osteoclasts (all P < .05). Furthermore, periapical lesions in ST2(-)/(-) mice contained increased percentages of T cells expressing interferon-γ, IL-17, tumor necrosis factor-α, and IL-6 (all P < .05). In comparison with WT mice, CD3+ receptor activator of nuclear factor kappa B ligand+ T cells were increased, whereas CD3+ osteoprotegerin+ T cells were decreased in the lesions of ST2(-)/(-) mice (both P < .05). CONCLUSIONS ST2 deletion increases inflammatory bone loss in experimental periapical lesions in mice, which is associated with enhanced Th1/Th17 cell mediated periapical immune responses and increased osteoclastogenesis.

Bilateral numb chin syndrome as a symptom of breast cancer metastasis in the mandible: a case report and discussion on the usefulness of cone-beam computed tomography to assess bone involvement in oral cancer

Although extremely rare, cancer metastases in the oral cavity are significant because they represent a sign of relapse of the primary malignancy and are difficult to diagnose because of their uncharacteristic clinical appearance. Numb chin syndrome is considered an important symptom and a harbinger of malignancy, especially in patients with a history of malignant disease. A 60-year-old female patient with a history of breast cancer complained of a 6-month history of bilateral numb chin syndrome. Cone-beam computed tomography scans revealed malignant characteristics in a bone lesion, comprising a bilateral ill-defined osteolytic process in the mandibular body. A malignancy arising from the breast tissue was confirmed by biopsy results. When numb chin syndrome is present, a proper step-by-step clinical algorithm must include a detailed patient history, clinical examination, three-dimensional imaging of the maxillofacial area, and biopsy. Cone-beam computed tomography may be a useful diagnostic tool for evaluating jaw bone invasion by tumors.

Expression of interleukin‐33 and its receptor ST2 in periapical granulomas and radicular cysts

BACKGROUND Interleukin-33 (IL-33) is a recently identified cytokine belonging to the IL-1 family and ligand for the IL-1 receptor-related protein ST2. IL-33/ST2 signaling plays a critical role in allergy, autoimmunity, and chronic inflammatory disorders, but its role in the pathogenesis of periapical lesions is unknown. We aimed to investigate the expression patterns of IL-33 and ST2 in human periapical lesions. METHODS Periapical lesions (n = 36) and healthy periapical tissues (n = 10) were evaluated by immunohistochemistry using antibodies specific for human IL-33 and ST2. Lesion samples were further analyzed by double immunofluorescence to assess IL-33/ST2 co-expression. RESULTS The numbers of IL-33- and ST2-positive fibroblasts were significantly higher in periapical lesions compared to healthy periapical tissues (both P < 0.05), while the numbers of IL-33- and ST2-positive endothelial cells were similar (both P > 0.05). There were no significant differences in the numbers of IL-33- and ST2-positive fibroblasts and endothelial cells between periapical granulomas and radicular cysts (all P > 0.05). Similarly, numbers of ST2-positive mononuclear cells did not differ between periapical granulomas and radicular cysts (P > 0.05). The majority of epithelial cells in radicular cysts were IL-33 positive, while the small proportion of epithelial cells was ST2 positive. Double immunofluorescence analysis revealed IL-33/ST2 co-expression in fibroblasts and endothelial cells. CONCLUSIONS IL-33 and ST2 are expressed in periapical granulomas and radicular cysts. Increased numbers of IL-33- and ST2-positive fibroblasts in periapical lesions when compared to healthy periapical tissues suggest that IL-33/ST2 signaling may be involved in periapical inflammation and tissue fibrosis.

Molecular and Cellular Mechanisms Involved in Mesenchymal Stem Cell-Based Therapy of Inflammatory Bowel Diseases

Mesenchymal stem cells (MSCs) are promising resource for the therapy of inflammatory bowel diseases (IBDs) on the grounds of their differentiation capabilities and immuno-modulatory characteristics. Results of clinical studies indicate that local application of MSCs is a secure and beneficial approach for the treatment of perianal fistulas while systemic application of MSCs leads to the attenuation or aggravation of IBDs. Herein, we emphasized molecular mechanisms and approaches that should improve efficacy of MSC-based therapy of IBDs.

Nanoparticles in Antiviral Therapy

Abstract In addition to general unavailability of specific antiviral therapeutics for a variety of viral diseases, usage of most antiviral drugs is linked to their limited solubility in aqueous media, short half-life time, and inadequate penetration to specified anatomic compartments. Accordingly, there is continuous effort to improve physicochemical characteristics of existing antiviral drugs. Since nanomaterials display remarkable physical and chemical properties, high surface area to volume ratio, and increased reactivity, new approaches for antiviral therapies include combinations of nanomaterials and current antiviral agents. Multivalent nanostructures, polymers, dendrimers, and liposomes can establish multivalent binding interactions with many biological systems and thus can target pathogenic interactions. There are reports about anitiviral activities of different metal nanoparticles, especially silver nanoparticles and their potential for treatment, prophylaxis, and control of viral infections. Integration of classic antiviral drugs, in the form of multiple ligands, onto nanostructures provides the advantages by creating a high local concentration of active molecules. This article will summarize the antiviral activity of different nanoparticle-based approaches currently available for the treatment of viral infections, and it will discuss metal nanoparticles as possible future antiviral drugs.

Platinum Complexes with Edda (Ethylenediamine -N, N - Diacetate) Ligands as Potential Anticancer Agents

Abstract The design of platinum based drugs is not a new field of interest. Platinum complexes are widely used as anticancer agents and currently, approximately 30 platinum(II) and platinum(IV) entered into some of the phases of clinical trials. A special place in today’s research belongs to platinum complexes with diammine ligands. A large number of edda (ethylenediamine- N, N’-diacetate)-type ligands and their corresponding metal complexes has been successfully synthesized. This article summarizes recent progress in research on edda-type-platinum complexes. Some of these agents achieves better effect compared to the gold standard (cisplatin). It has been shown that there is a possible relationship between the length of the ligand ester group carbon chain and its cytotoxic effect. In most cases the longer the ester chain is the greater is the antitumor activity. Of particular interest are the noticeable effects of some new platinum compound with edda-type ligand on cell lines that are known to have a high level of cisplatin-resistance. Exanimate complexes appear to have a different mode of mechanism of action compared with cisplatin which includes apoptotic and necrotic cell death. There are indications that further investigations of these compounds may be very useful in overcoming the problems associated global cancer statistic.