Anti-inflammatory and immunomodulatory effects of Biodentine on human periapical lesion cells in culture.

AIM: To evaluate the effect of Biodentine eluate on cytotoxicity and production of pro- and anti-inflammatory cytokines and osteodestructive/osteoprotective cytokines in cultures of human periapical lesion cells. METHODOLOGY: Conditioned Biodentine Medium (CBM) was prepared according to ISO 10993-12, by incubating Biodentine in RPMI medium (0.2 g mL-1 ) for 3 days at 37 °C. CBM contained both released microparticles and leachable soluble components. Inflammatory cells were isolated from 22 human periapical lesions after apicectomy or tooth extraction, by collagenase/DNase digestion, and cultured in several dilutions of CBM. The composition of periapical lesion cells was determined by morphological criteria, cytotoxicity was quantified by MTT and flow cytometric apoptosis/necrosis assays, whereas the levels of produced cytokines in cell culture supernatants were measured by flow cytometry and ELISA. Student t-test and Friedman test with Dunn's post-test were used for comparison of parametric and nonparametric variables, respectively. RESULTS: Undiluted (100%), 75% and 50% CBM were cytotoxic for periapical lesion cells due to induction of both necrosis (100% CBM) and apoptosis (75% and 50% CBM). Noncytotoxic concentrations of CBM (25%) inhibited the production of pro-inflammatory cytokines: TNF-α, (P < 0.005); IL-1ß (P < 0.01); IL-6 (P < 0.005) and chemokines IL-8: (P < 0.005); MCP-1 (P < 0.005), stimulated the production of anti-inflammatory cytokine (IL-10; P < 0.005), Th2 cytokines: IL-4, IL-5 and IL-33 (all P < 0.01), and IL-17A (P < 0.01). The concentration of CBM (12.5%) inhibited the production of IL-6 (P < 0.05), IL-8 (P < 0.01) and MCP-1 (P < 0.005) and augmented the production of IL-10 (P < 0.05). No significant effects on Th1-related cytokines (IFN-γ and IL-12) and IL-23 were detected with 25% and 12.5% CBM concentrations. Both CBM concentrations inhibited the production of osteolytic receptor activator of nuclear factor kappa-Β ligand (RANKL), dose dependently (P < 0.005 and P < 0.01, respectively). Higher CBM concentrations decreased RANKL/osteoprotegerin (OPG) ratio (P < 0.05), without significant influence on the levels of osteoprotective OPG. CONCLUSION: Biodentine possesses immunomodulatory properties by suppressing pro-inflammatory and augmenting anti-inflammatory cytokines. Together with the reduction of osteodestructive mediators, this novel root-end filling cement could be beneficial for healing and bone reparation after the surgical treatment of periapical lesions.

[BASIC PRINCIPLES OF SURGICAL TREATMENT OF CHRONIC WOUNDS ­ SHARP DEBRIDEMENT].

The ever improving health standards in terms of quality and more efficient health care result in an increase in life expectancy, thus increasing the number of elderly people in the population. A higher level of activity in elderly population leads to greater incidence of injuries, and on the other hand, there is an increasing number of comorbidities. Circulatory disorders, diabetes mellitus, metabolic imbalances, etc. and a reduced biological potential of tissue regeneration result in an increased number of chronic wounds that pose a significant health, social and economic burden on the society. These conditions require significant involvement of medical and non-medical staff in pre-hospital institutions. Significant material and other health care resources are allocated for the treatment of chronic wounds. These conditions result in a lower quality of life of patients and their families and caregivers. Debridement is a crucial medical procedure for the treatment of acute and chronic wounds. The result of debridement is removal of all barriers within and around the wound that obstruct physiological processes of wound healing. Debridement is a repeating process when indicated. There are several types of debridement, each with its advantages and disadvantages. The method of debridement should be determined by the physician or other professional trained person on the basis of wound characteristics and in accordance with their expertise and capabilities. In the same wound, we can combine different types of debridement, all with the goal of faster and better wound healing.

Depressive disorder as possible risk factor of osteoporosis.

Hypothalamo-pituitary-adrenal (HPA) axis is a very complicated control system playing an important role in stress reaction, where glucocorticoids suppress the autonomic (vegetative), endocrine, immunologic and psychic responses to stressful stimuli. We described the marked clinical, physiological, and biochemical connection between osteoporosis and major depressive disorder (MDD). Both conditions are associated with a hyperactive HPA axis and LC/NE system, and hence with increased CRH, cortisol, and catecholamine secretion. There are numerous states or diseases associated with osteoporosis and we were looking for a hypercorticism value as a one of these. Some recent studies demonstrated that earlier history of MDD was associated with marked osteoporosis. In MDD there are two well-documented biochemical abnormalities: hypercortisolism and its resistance to dexamethasone suppression. The present study included 31 MDD patients (19 males and 12 females, mean age 37 +/- 1.3, age range 29-41 years), and 17 healthy male volunteers (mean age 39 +/- 1.6, age range 34-45 years). In each of our patients 24-hour urinary free cortisol, serum cortisol level at 8 a.m. and 5 p.m., cortisol in dexamethasone suppression test and bone mineral density were measured. We have, therefore, analyzed a group of young men and women with normal menstrual cycles, who were without signs of osteoporosis in the beginning, and who received anti-depressive therapy for many years. Analysis showed that increased levels of cortisol and the occurrence of osteoporosis, that developed as the result of elevated cortisol level. For our workshop we used nonparametric rang-correlation with Spearman's rho = -0.805, with statistic significant at the 0.01 level (2-tailed). Patients under long-term history of depression could develop a very stronger type of osteoporosis i.e. it is before known that the patients with untreated Cushing syndrome developed hard osteoporosis.

Diseases of the lips.

The vermilion of the lips was conceptualized by Jean Darier as the semi-mucosa. The anatomy of the lips is transitional from skin to mucous membrane. This article emphasizes inflammatory diseases of the lips known as cheilitis. Angular cheilitis is a reactive process with several possible causes, including infections, mechanical, nutritional deficiency, and various dermatoses. Contact cheilitis may be caused by a primary irritant or a delayed hypersensitivity allergic reaction to contactants. Plasma cell cheilitis is a reactive periorificial mucositis. Exfoliative cheilitis is also a reactive process, probably secondary to factitious activity of the patient. Cheilitis glandularis is a chronic inflammatory disorder of the labial salivary glands and their ducts. There are three forms: simple, superficial suppurative, and deep suppurative. A premalignant potential is present in cheilitis glandularis. Cheilitis granulomatosa is one manifestation of orofacial granulomatosis. The granulomatous conditions of Melkersson-Rosenthal syndrome, sarcoidosis, and Crohn's disease may be associated with cheilitis granulomatosa or it may stand alone as Miescher's cheilitis. Actinic cheilitis is another premalignant form of cheilitis that is amenable to a variety of therapeutic modalities.