Maria Greabu

Salivary biomarkers: Relationship between oxidative stress and alveolar bone loss in chronic periodontitis

Abstract Objectives. Oxidative stress is implicated in the pathogenesis of many systemic and oral diseases such as periodontal disease. The main aim of this study is to explore a possible association between salivary markers of OS and alveolar bone loss. Materials and methods. The study included 20 patients with chronic periodontitis and 20 controls. Salivary OS biomarkers 8-hidroxy-desoxguanosine (8-HOdG), malondialdehyde (MDA), uric acid, total antioxidant capacity (TAC) and glutathione peroxidase (GPx) were evaluated. Bone loss markers such as C-terminal telopeptide of type I collagen (CTX I), matrix metalloproteinases-8 (MMP-8), osteocalcin and 25-hydroxy vitamin D3 (25- OH D) were detected in this study. The methods included general biochemical tests and ELISA. Results. Salivary 8-OHdG, MDA levels were significantly higher in the chronic periodontitis group compared with controls (p < 0.05). Salivary activities for uric acid, TAC and GPx were significantly decreased in patients with chronic periodontitis vs controls (p < 0.05). Salivary levels for CTX I, MMP-8, 25-OH D and Osteocalcin were significantly higher in the chronic periodontitis group compared to the controls (p < 0.05). A significant positive correlation was observed between salivary levels of MDA and CTX I. Significant negative correlations between uric acid and CTX I and between MMP-8 and uric acid have been found. Significant positive correlations were observed between CTX I, MMP-8, 25-OH D, osteocalcin and clinical parameters of periodontal disease. Conclusions. Important oxidative stress associated with alveolar bone loss biomarkers can be detected in saliva of patients with periodontal disease.

Salivary aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase : possible markers in periodontal diseases?

Abstract Background: Saliva can be used as a diagnostic fluid in medicine. Components of saliva proposed as disease markers include enzymes (alkaline phosphatase, esterase, glucuronidase, aminopeptidase), immunoglobulins (IgA, IgG), and hormones (steroid hormones). Many of these salivary components appeared to be useful biochemical markers of the evolution of periodontal disease, for which salivary analysis can offer a cost-effective approach for monitoring the disease. The salivary components proposed as markers for periodontal disease activity are aspartate aminotransferase (AST), alkaline phosphatase (ALP), aminopeptidases, and glucuronidases. The purpose of our study was to illustrate the influence of periodontal disease on the level of salivary AST, alanine aminotransferase (ALT) and ALP. Methods: All clinical periodontal examinations were performed by the same periodontist. All patients included in the study presented a probing depth >5mm, bleeding on probing and alveolar bone loss >40%. Salivary AST, ALT and ALP activities were measured using DiaSys analysis kits from Diagnostic Systems. The methods were adapted for saliva. Results: Salivary AST activity in patients with periodontal disease was significantly increased (p<0.01) (median 81.75±23U/L) compared with controls (15.25±10.5U/L). Salivary ALT activity was not significantly modified in saliva from patients with periodontal disease compared with the control group. Our results showed a significant (p<0.01) increase in salivary ALP activity (34.38±1.5U/L) in patients with periodontal disease compared with controls (6.6±4.2U/L). Conclusions: Our results revealed that periodontal destruction such as periodontal pockets, gingival bleeding and suppuration are related to higher ALP and AST levels in saliva. Salivary AST could be used as a useful marker for monitoring periodontal disease. The increase in salivary ALP activity in periodontitis demonstrated could be associated with alveolar bone loss, a key feature of periodontal disease. More studies are necessary to evaluate which specific clinical, microbiological and histological characteristics of periodontal disease are associated with elevated levels of AST and ALP in saliva.

Oral keratinocyte stem/progenitor cells: specific markers, molecular signaling pathways and potential uses.

Oral keratinocyte stem cells reside in the basal layers of the oral epithelium, representing a minor population of cells with a great potential to self-renew and proliferate over the course of their lifetime. As a result of the potential uses of oral keratinocyte stem cells in regenerative medicine and the key roles they play in tissue homeostasis, inflammatory conditions, wound healing and tumor initiation and progression, intense scientific efforts are currently being undertaken to identify, separate and reprogram these cells. Although currently there is no specific marker that can characterize and isolate oral keratinocyte stem cells, several suggestions have been made. Thus, different stem/progenitor-cell subpopulations have been categorized based on combinations of positive and/or negative membrane-surface markers, which include integrins, clusters of differentiation and cytokeratins. Important advances have also been made in understanding the molecular pathways that govern processes such as self-renewal, differentiation, proliferation, wound healing and programmed cell death. A thorough understanding of stem-cell biology and the molecular players that govern cellular fate is paramount in the quest for using stem-cell-derived therapies in the treatment of various oral pathologies. The current review focuses on recent advances in understanding the molecular signaling pathways coordinating the behavior of these cells and in identifying suitable markers used for their isolation and characterization. Special emphasis will also be placed on the roles played by oral keratinocyte stem and progenitor cells in normal and diseased oral tissues and on their potential uses in the fields of general medicine and dentistry.

From Normal Skin to Squamous Cell Carcinoma: A Quest for Novel Biomarkers

Squamous cells carcinoma (SCC) is the second most frequent of the keratinocyte-derived malignancies after basal cell carcinoma and is associated with a significant psychosocial and economic burden for both the patient himself and society. Reported risk factors for the malignant transformation of keratinocytes and development of SCC include ultraviolet light exposure, followed by chronic scarring and inflammation, exposure to chemical compounds (arsenic, insecticides, and pesticides), and immune-suppression. Despite various available treatment methods and recent advances in noninvasive or minimal invasive diagnostic techniques, the risk recurrence and metastasis are far from being negligible, even in patients with negative histological margins and lymph nodes. Analyzing normal, dysplastic, and malignant keratinocyte proteome holds special promise for novel biomarker discovery in SCC that could be used in the future for early detection, risk assessment, tumor monitoring, and development of targeted therapeutic strategies.

Hydrogen Sulfide, Oxidative Stress and Periodontal Diseases: A Concise Review

In the past years, biomedical research has recognized hydrogen sulfide (H2S) not only as an environmental pollutant but also, along with nitric oxide and carbon monoxide, as an important biological gastransmitter with paramount roles in health and disease. Current research focuses on several aspects of H2S biology such as the biochemical pathways that generate the compound and its functions in human pathology or drug synthesis that block or stimulate its biosynthesis. The present work addresses the knowledge we have to date on H2S production and its biological roles in the general human environment with a special focus on the oral cavity and its involvement in the initiation and development of periodontal diseases.

Current Uses of Poly(lactic-co-glycolic acid) in the Dental Field: A Comprehensive Review

Poly(lactic-co-glycolic acid) or PLGA is a biodegradable polymer used in a wide range of medical applications. Specifically PLGA materials are also developed for the dental field in the form of scaffolds, films, membranes, microparticles, or nanoparticles. PLGA membranes have been studied with promising results, either alone or combined with other materials in bone healing procedures. PLGA scaffolds have been used to regenerate damaged tissues together with stem cell-based therapy. There is solid evidence that the development of PLGA microparticles and nanoparticles may be beneficial to a wide range of dental fields such as endodontic therapy, dental caries, dental surgery, dental implants, or periodontology. The aim of the current paper was to review the recent advances in PLGA materials and their potential uses in the dental field.

Organic Nanomaterials and Their Applications in the Treatment of Oral Diseases

There is a growing interest in the development of organic nanomaterials for biomedical applications. An increasing number of studies focus on the uses of nanomaterials with organic structure for regeneration of bone, cartilage, skin or dental tissues. Solid evidence has been found for several advantages of using natural or synthetic organic nanostructures in a wide variety of dental fields, from implantology, endodontics, and periodontics, to regenerative dentistry and wound healing. Most of the research is concentrated on nanoforms of chitosan, silk fibroin, synthetic polymers or their combinations, but new nanocomposites are constantly being developed. The present work reviews in detail current research on organic nanoparticles and their potential applications in the dental field.

Gene Expression and Proteome Analysis as Sources of Biomarkers in Basal Cell Carcinoma.

Basal cell carcinoma (BCC) is the worlds leading skin cancer in terms of frequency at the moment and its incidence continues to rise each year, leading to profound negative psychosocial and economic consequences. UV exposure is the most important environmental factor in the development of BCC in genetically predisposed individuals, this being reflected by the anatomical distribution of lesions mainly on sun-exposed skin areas. Early diagnosis and prompt management are of crucial importance in order to prevent local tissue destruction and subsequent disfigurement. Although various noninvasive or minimal invasive techniques have demonstrated their utility in increasing diagnostic accuracy of BCC and progress has been made in its treatment options, recurrent, aggressive, and metastatic variants of BCC still pose significant challenge for the healthcare system. Analysis of gene expression and proteomic profiling of tumor cells and of tumoral microenvironment in various tissues strongly suggests that certain molecules involved in skin cancer pathogenic pathways might represent novel predictive and prognostic biomarkers in BCC.

Volatile Organic Compounds Expression in Different Cell Types: An In Vitro Approach

The relationship between volatile organic compounds (VOCs) in exhaled breath and local or general pathologies is a most interesting field of research. Different chemical signatures have been observed in breath from patients with lung, cardiovascular, gastro-intestinal, liver, renal or mental diseases, diabetes, different types of cancer or physiological conditions such as pregnancy. Important classes of volatile compounds are hydrocarbons, ketones, aldehydes, alcohols, organic acids, sulfur- and nitrogen-containing compounds, aromatics, esters and terpenes. Current data suggests that depending on the affected tissue or organ, volatiles can have a specific profile. However, to date, information on the biochemical origin of these volatiles is rare. Prominent exceptions are isoprene or acetone, where biochemical background information can be given, and the exhalation kinetics has been determined (in part) by real-time analysis of exhaled breath. One possible approach for elucidating the biochemical background of other volatile biomarkers specific to a certain biological process is the in vitro headspace investigation of cell lines, looking at normal proliferation but also on necrosis and apoptosis and at the influence of various biologically active compounds added to the cell culture medium. The present work reviews the current advances in VOCs research in relation with in vitro cell cultures.

Oxidative stress and volatile organic compounds: interplay in pulmonary, cardio-vascular, digestive tract systems and cancer

Abstract Oxidative stress (OS) can be defined as an imbalance between antioxidant systems and various pro-oxidants. This loss of balance is closely associated with initiation and development of a wide range of systemic or organ specific diseases. Exhaled breath of healthy humans contains a large number of volatile organic compounds (VOCs) derived from cellular metabolism, released by microorganisms or taken up from the environment. Qualitative or quantitative changes in their composition are associated with diseases and various pathological conditions, also characterized by increased production of reactive oxygen species (ROS), such as superoxide radical, hydrogen peroxide, hydroxyl anion, peroxinitrite, etc. Several volatile organic compounds such as ethane and pentane are direct end-products of the reaction of ROS with various biological compounds (e.g., lipid peroxidation, DNA or protein damage). Being able to accurately identify ROS-generated VOCs could be of particular importance in devising sensitive tests that can diagnose and follow-up oxidative stress-related diseases. This review describes current knowledge on the associations between oxidative stress and free radicals and the release of several marker volatile organic compounds in a number of diseases. A special focus will be placed on such VOCs in the cardiovascular pathologies, pulmonary diseases and gastro-intestinal tract affections. Graphical Abstract