Bone microRNA-21 as surgical stress parameter is associated with third molar postoperative discomfort.

OBJECTIVE: To evaluate an association between bone levels of inflammation/oxidative stress mediators and postoperative discomfort after third molar conventional or piezosurgery. MATERIAL AND METHODS: Twenty-six subjects with bilaterally impacted mandibular third molars, who underwent either piezo or conventional surgery, were included in a split-mouth design study. MicroRNA-21 (miR-21) expression, interleukin-1 beta (IL-1ß), and vascular endothelial growth factor (VEGF) proteins, as well as superoxide dismutase (SOD) activity in alveolar bone, were evaluated. Pain intensity, the first pain appearance, analgesic first use and total dose taken, trismus, and swelling were clinically recorded. RESULTS: MiR-21 expression was higher while VEGF protein was lower in piezosurgery vs. conventional groups. The differences in IL-1ß protein and SOD activity were not significant between groups. The pain intensity on the first day was significantly decreased in piezosurgery group. The first pain appearance and the first analgesic taken were reported sooner in conventional vs. piezosurgical group. Significantly pronounced trismus on the third day following conventional surgery was found. In conventional group, significantly increased trismus was observed on the third compared to the first postoperative day. MiR-21 showed significant correlation with the first pain appearance. CONCLUSION: Delayed onset of less pronounced postoperative pain after piezosurgical vs. conventional extraction of impacted lower third molar was significantly associated with expression of bone miR-21. CLINICAL RELEVANCE: Alveolar bone miR-21 may reflect surgical stress and is associated with third molar postoperative pain onset.

Effect of Aging and Carotid Atherosclerosis on Multifractality of Dental Pulp Blood Flow Oscillations.

INTRODUCTION: Age-related changes of dental pulp tissue and atherosclerosis of carotid arteries as its feeding arteries could influence the functionality of pulpal circulation. The objective of our study was to evaluate the effect of aging (physiological process) and carotid bifurcation atherosclerosis (pathologic process) on the pulpal microcirculatory system using multifractal analysis of the laser Doppler flowmetry signal. METHODS: Three groups of 10 subjects were enrolled in the study: the young group (healthy subjects, 20-25 years), the middle-aged group (healthy subjects, 50-60 years), and the clinical group (subjects with carotid bifurcation atherosclerosis, 50-60 years). Pulpal blood flow (PBF) signals recorded by laser Doppler flowmetry were assessed by multifractal analysis that estimates Hölder exponents of the signal. PBF levels, the average mean values, and the range of Hölder exponents were obtained. RESULTS: PBF levels were significantly higher in the young group compared with the middle-aged and clinical groups, and the difference between the middle-aged and clinical groups was not statistically significant. The range of the Hölder exponents was narrower in the middle-aged and clinical groups than in the young group and narrower in the clinical group than in the middle-aged group. The average mean value of Hölder exponents was significantly higher in the young group than in the middle-aged and clinical groups, whereas there was no significant difference between the middle-aged and clinical groups. CONCLUSIONS: Our study investigating the multifractality of the PBF signal showed that the aging process and carotid atherosclerosis could affect the complex structure of PBF oscillations and contribute to a better understanding of pulpal hemodynamics.

Mandibular lateral deviation induces alteration in vascular endothelial growth factor expression and oxidative stress/nitric oxide generation in rat condyle, synovial membrane and masseter muscle.

OBJECTIVE: We aimed to investigate alteration in cellular signaling mediated by vascular endothelial growth factor (VEGF) and parameters of oxidative stress/nitric oxide generation, superoxide dismutase (SOD) and neuronal nitric oxide synthase (nNOS), underlying altered functional mechanical loading of TMJ (temporomandibular joint) during lateral mandibular deviation. DESIGN: Thirty-eight 5-week-old male Wistar rats were divided into experimental group, which received acrylic resin appliance that shifted mandible to the left during closure, and control group. Computed tomography and histomorphometry were used for condyle analyses, while samples of condyle, synovial membrane and m. masseter were analyzed with enzyme-linked immunosorbent assay and spectrophotometry to determine VEGF and nNOS protein concentrations, and SOD activity. RESULTS: Experimental group of rats developed smaller and asymmetrical mandibles. Less of new bone and cartilage formation and larger bone marrow cavities area were found in the experimental group. Higher VEGF expression in condyle and m. masseter as well as higher nNOS expression in m. masseter and synovial membrane were found in the experimental compared to the control group. Alteration of SOD activity was found in m. masseter and synovial membrane in the experimental group. CONCLUSIONS: Lateral mandibular deviation induces mandibular and condylar morphological changes as well as significant cellular signaling alterations in condyle, synovial membrane and masticatory muscle. Cellular VEGF protein overexpression and oxidative stress/nitric oxide disbalance could be the mechanisms underlying unbalanced functional TMJ loading due to mandibular deviation.

Leukocyte- and platelet-rich fibrin as graft material improves microRNA-21 expression and decreases oxidative stress in the calvarial defects of diabetic rabbits.

OBJECTIVE: Leukocyte- and platelet-rich fibrin (L-PRF) represents a natural, low-cost product which may promote tissue healing by mechanisms not fully elucidated. Diabetes mellitus (DM) disrupts bone healing by inducing inflammation and oxidative stress (OS), mechanisms regulated by microRNAs (miRs). The aim of the present study was to investigate the microRNA-21 (miR-21) involvement in diabetic bone regeneration using L-PRF alone or in combination with a standard grafting material. DESIGN: After the induction of diabetes (alloxan 100 mg/kg), four cranial osteotomies were made in diabetic (n = 12) and non-diabetic (n = 12) rabbits: one was left empty and the remaining three were grafted with L-PRF, bovine hydroxyapatite (Bio-Oss®) and L-PRF + Bio-Oss®. Two and eight weeks postoperatively, the samples were harvested for miR-21 expression (Real-time RT-PCR) and enzyme-linked immunosorbent assay analyses. RESULTS: Diabetic rabbits showed decreased miR-21 and matrix metalloproteinase-9 (MMP-9) protein expression while increased malondialdehyde (MDA) levels two weeks postoperatively; however, there were no significant differences in miR-21 and MMP-9 levels between diabetic and non-diabetic rabbits in samples taken eight weeks postoperatively. Application of L-PRF and L-PRF + Bio-Oss® improved miR-21 and MMP-9 and decreased MDA levels while Bio-Oss® alone enhanced superoxide dismutase (SOD) activity levels in diabetic rabbits. CONCLUSION: L-PRF alone or in combination with bovine hydroxyapatite as bone graft could be beneficial in DM since it seems to improve inflammation-modulatory miR-21 expression and decreases oxidative stress.

Effect of neuropeptide Y on norepinephrine-induced constriction in the rabbit facial artery after carotid artery occlusion.

BACKGROUND/AIM: Atherosclerotic-occlusive changes could be observed in orofacial branches of the external carotid artery. Atherosclerosis-induced ischemia caused alteration in production and release of endothelial factors. The aim of this study was to investigate the influence of carotid artery occlusion (10, 30 and 60 min) on vascular effects of norepinephrine (NOR) and neuropeptide Y (NPY) in the isolated glandular branch of the rabbit facial artery, the main feeding artery for the submandibular gland. METHOD: Changes in isometric tension were recorded in organ bath studies with arterial rings, before and after carotid artery occlusion. RESULTS: Concentration-dependent vasocontractile effect of NOR was significantly augmented after 30 and 60 min of carotid occlusion, but only in the rings with intact endothelium. Given alone, NPY showed no effect in isolated glandular branch of the rabbit facial artery, but enhanced NOR vasoconstriction in all the investigated rings. NOR vasocontractile effect enhancement in the presence of NPY was attenuated after 30 and 60 min of carotid occlusion. Also, enhancement of NOR vasoconstriction by NPY was significantly higher in endothelium-intact rings compared to endothelium-denuded rings obtained after 30 and 60 min of carotid occlusion. CONCLUSION: The present investigation provides results of increased vasocontractile effect of NOR and decreased enhancing effect of NPY on NOR vasoconstriction in the rabbit facial artery after carotid occlusion that is related to altered endothelium function.

Benzodiazepines utilization and self-medication as correlates of stress in the population of Serbia.

BACKGROUND: High consumption of benzodiazepines (BDZ) occurs in populations exposed to stress. In the last decade of the 20th century, when the population of Serbia experienced increasing economic hardships due to the civil war in former Yugoslavia, UN sanctions and air raids in 1999, diazepam became the most frequently prescribed drug. This period was also characterized by the free marketing of all drugs, which made them available without prescription. OBJECTIVE: To investigate the consumption and the pattern of use of BDZ in the population of Belgrade and Serbia in the period of 1990-2001. MATERIALS AND METHODS: Data on benzodiazepines prescribing and on wholesale in general population of Belgrade and Serbia were collected. In a cross-sectional study of drug prescribing in general practice data were obtained from 1800 patient records in the primary health care centers in Serbia. Statistical analysis was performed by using standard non-parametric tests. RESULTS: Annual rates of BDZ prescribing in Belgrade from 1990 to 1999 were rather uniform (approx. 25 DDD/1000 inhabitants/day), with slight tendency to decrease. In Serbia as a whole, there were significant differences in the annual prescribing rates over the period 1998-2000. The wholesale of BDZ in Serbia significantly increased between 1991 and 2001, with the peak of 133 DDD/1000 inhabitants/day in 1999. The wholesale of BDZ was significantly greater that the rates of prescribing in corresponding years. Over the 10 year period, the numbers of visits to GPs and psychiatrists and the number of neurotic diagnoses were significantly reduced. The use of BDZ in psychiatric hospital increased significantly in 1999 as compared to 1998, although the number of admissions and the occupancy of hospital beds were reduced. In primary health care, diazepam was the most frequently prescribed drug predominantly for non-psychiatric diagnoses. CONCLUSIONS: It is concluded that in the last decade, the utilization of BDZ was increased in the population of Belgrade and Serbia, indicating a clear trend to self-medication, particularly in the period of acute war crisis.