Due to the high biotolerance, favourable mechanical properties, and osseointegration ability, titanium is the basic biomaterial used in maxillofacial surgery. The passive layer of titanium dioxide on the surface of the implant effectively provides anticorrosive properties, but it can be damaged, resulting in the release of titanium ions to the surrounding tissues. The aim of our work was to evaluate the influence of Ti6Al4V titanium alloy on redox balance and oxidative damage in the periosteum surrounding the titanium miniplates and screws as well as in plasma and erythrocytes of patients with mandibular fractures. The study included 31 previously implanted patients (aged 21–29) treated for mandibular fractures and 31 healthy controls. We have demonstrated increased activity/concentration of antioxidants both in the mandibular periosteum and plasma/erythrocytes of patients with titanium mandibular fixations. However, increased concentrations of the products of oxidative protein and lipid modifications were only observed in the periosteum of the study group patients. The correlation between the products of oxidative modification of the mandible and antioxidants in plasma/erythrocytes suggests a relationship between the increase of oxidative damage at the implantation site and central redox disorders in patients with titanium miniplates and screws.
The aim of the study was to evaluate the effect of titanium bone fixations on mitochondrial activity, reactive oxygen species (ROS) production, glutathione metabolism, and selected markers of oxidative/nitrosative stress in the periosteum-like tissue of patients treated with mandible fractures. The study group consisted of 30 patients with bilateral fractures of the mandible body eligible for surgical treatment. Our study is the first one that indicates disturbances of mitochondrial activity as well as a higher production of ROS in the periosteum-like tissue covering titanium fixations of the mandible. We also found significantly higher levels of reduced glutathione and enhanced activity of glutathione reductase in the periosteum homogenates of patients in the study group compared to the control group. Levels of nitrosative (S-nitrosothiols, peroxynitrite, nitrotyrosine) and oxidative stress biomarkers (malondialdehyde, protein carbonyls, dityrosine, kynurenine, and N-formylkynurenine) were statistically elevated in periosteum-like tissue covering titanium fixations. Although exposure to titanium fixations induces local antioxidant mechanisms, patients suffer oxidative damage, and in the periosteum-like tissue the phenomenon of metallosis was observed. Titanium implants cause oxidative/nitrosative stress as well as disturbances in mitochondrial activity.
Titanium miniplates and screws are commonly used for fixation of jaw fractured or osteotomies. Despite the opinion of their biocompatibility, in clinical practice symptoms of chronic inflammation around the fixation develop in some patients, even many years after the application of miniplates and screws. The cause of these complications is still an unanswered question. Taking into account that oxidative stress is one of the toxic action of titanium, we have evaluated the antioxidant barrier as well as oxidative stress in the erythrocytes, plasma and periosteum covering the titanium fixation of the jaw. The study group was composed of 32 patients aged 20–30 with inserted miniplates and screws. The antioxidant defense: catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase-1 (SOD1), uric acid (UA), total antioxidant capacity (TAC), as well as oxidative damage products: advanced oxidation protein products (AOPP), advanced glycation end products (AGE), dityrosine, kynurenine, N-formylkynurenine, tryptophan, malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), total oxidant status (TOS), and oxidative status index (OSI) were evaluated. SOD1 activity (↓37%), and tryptophan levels (↓34%) showed a significant decrease while AOPP (↑25%), TOS (↑80%) and OSI (↑101%) were significantly elevated in maxillary periosteum of patients who underwent bimaxillary osteotomies as compared to the control group. SOD-1 (↓55%), TAC (↓58.6%), AGE (↓60%) and N-formylkynurenine (↓34%) was statistically reduced while AOPP (↑38%), MDA (↑29%), 4-HNE (↑114%), TOS (↑99%), and OSI (↑381%) were significantly higher in the mandibular periosteum covering miniplates/screw compared with the control tissues. There were no correlations between antioxidants and oxidative stress markers in the periosteum of all patients and the blood. As exposure to the Ti6Al4V titanium alloy leads to disturbances of redox balance in the periosteum surrounding titanium implants of the maxilla and the mandible so antioxidant supplementation should be recommended to the patients undergoing treatment of dentofacial deformities with the use of titanium implants. The results we obtained may also indicate a need to improve the quality of titanium jaw fixations through increase of TiO2 passivation layer thickness or to develop new, the most highly biodegradable materials for their production.
Despite high biocompatibility of titanium and its alloys, this metal causes various side effects in the human body. It is believed that titanium biomaterials may induce an innate/adaptive immune response. However, still little is known about changes caused by titanium mandible implants, particularly with regard to bone healing. The latest studies showed disturbances in the antioxidant barrier, increased oxidative/nitrosative stress, as well as mitochondrial abnormalities in the periosteum covering titanium mandible fixations; nevertheless, the impact of titanium implants on free radical production, inflammation, and mandible apoptosis are still unknown. Because severe inflammation and apoptosis are among the main factors responsible for disturbances in osteointegration as well as implant rejection, this study is the first to evaluate pro-oxidant enzymes, cytokines as well as pro- and anti-apoptotic proteins in the periosteum of patients with a broken jaw, treated with titanium miniplates and miniscrews. The study group consisted of 29 patients with double-sided fracture of the mandible body requiring surgical treatment. We found significantly higher activity of NADPH oxidase and xanthine oxidase as well as enhanced rate of free radical production in the periosteum of patients in the study group compared to the control group. The markers of inflammation [interleukin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), transforming growth factor β (TGF-β) and β-glucuronidase (GLU)] as well as apoptosis [Bax, Bax/Bcl-2 ratio, caspase-3 (CAS-3) and nitric oxide (NO)] were significantly elevated in periosteum covering titanium fixations compared to the control group. In the study group, we also demonstrated an increased content of titanium on the periosteum surface, which positively correlated with CAS-3 activity. The study led us to the conclusion that titanium mandible implants increase the production of pro-inflammatory cytokines, and enhance free radical generation in the periosteum covering titanium miniplates and miniscrews. Additionally, exposure to Ti6Al4V titanium alloy induces apoptosis in the mandible periosteum. However, no clinical signs of the said phenomena have been observed.
The aim of the study was a determination of the levels of nitric oxide (NO) and its biological markers such as malonyldialdehyde (MDA) and nitrotyrosine in the serum of patients with squamous cell carcinoma (SCC) of the oral cavity and identification of the relationships between NO and those markers. These studies were performed on patients with SCC of the oral cavity before and after treatment. Griess reaction was used for the estimation of the total concentration of NO in serum. The nitrotyrosine level in serum was assessed with an enzyme-linked immunosorbent assay (ELISA) kit, and MDA level using a spectrophotometric assay. Higher concentrations of NO in blood serum were determined in patients with stage IV of the disease before treatment in comparison to the control group and patients with stages II and III of the disease. Moreover, higher concentrations of MDA and nitrotyrosine were determined in the serum of patients in all stages of the disease in comparison to healthy people. After treatment, lower concentrations of NO in the serum of patients with stage IV of the disease were observed in comparison to the amounts obtained prior to treatment. In addition, lower levels of nitrotyrosine in the serum of patients with all stages of the disease were recorded, whereas higher concentrations of MDA were determined in these patients in comparison to results obtained before treatment. The compounds formed with the contribution of NO, such as MDA and nitrotyrosine, may lead to cancer progression in patients with SCC of the oral cavity, and contribute to formation of resistance to therapy in these patients as well. Moreover, the lack of a relationship between concentrations of NO and MDA, and between NO and nitrotyrosine in serum suggests that the process of lipid peroxidation and nitration in patients with SCC does not just depend on NO.
Available data indicating a role for neutrophils in the tumor-host reactions are controversial. In 37 patients with oral cavity squamous cell carcinoma (OSCC), we investigated the expression of a tumor-promoting, proliferation-inducing ligand (APRIL) molecule by peripheral blood neutrophils isolated from blood samples collected at presentation and three weeks after surgery, and the serum levels of TGF- in the same samples. Additionally, we investigated the consequences of TLR4 activation by LPS for the synthesis of APRIL by those cells.The levels of mRNA for APRIL and TLR4 were measured using a real-time PCR method. Western blot analysis was used to assay the expressions of APRIL and ERK1/2 in cell lysates. The results of the present study revealed the unfavorable features of the detection, in the blood, of neutrophils displaying an enhanced expression of the tumor-promoting APRIL molecule. The increased expression and release of APRIL accompanying advanced stages of disease demonstrated by these cells, combined with the increased number of neutrophils, may be an important marker of disease progression in the patient group examined. Simultaneously, an increased level of circulating TGF- in the serum of these patients appeared to be associated with the overexpression of APRIL in their neutrophils. In contrast to the healthy controls, TLR4 expression and the ERK1/2 signaling pathway appear to play only minor roles in APRIL induction in the cells of patients with cancer. The changes presented in the current study suggest that modulation of the expression of tumor-promoting APRIL, in addition to TRAIL and BAFF, might be taken into account in the development of new strategies for supportive immunotherapy of OSCC disease and possibly for other types of neoplasm as well.Key words: oral cavity squamous cell carcinoma (OCSCC), a proliferation-inducing ligand (APRIL), polymorphonuclear neutrophils (PMNs), Toll-like receptor 4 (TLR4), the extracellular signal-regulated kinases 1/2 (ERK1/2), transforming growth factor  (TGF-)
Background: Concrescent teeth belong to the group of double teeth with disturbed anatomy of shape and structure. The concrescence consists of the aggregation of root cementum of adjacent teeth. This anomaly usually concerns the upper teeth in the lateral part of the jaw. Concrescent teeth can be treated conservatively, endodontically, orthodontically and surgically. Objective: The aim of this article is to present the case of the concrescence of upper teeth, a second molar tooth with an impacted third molar, and to draw the attention of clinicians to this rare anomaly that may cause medical and legal problems. Case presentation: This article presents the case of a 53-year-old woman who reported to the dentist’s office to extract tooth 17 due to chronic periodontitis and an impacted and abnormally placed tooth 18. Result: During the extraction, concrescence of the teeth was noted. The teeth were removed, and the alveoli were surgically treated. The postoperative period was uncomplicated. Conclusion: In this paper, the authors draw the attention of clinicians to the fact that the occurrence of concrescent teeth in clinical practice is rare and that it is difficult to diagnose this anomaly on the basis of routine radiological diagnostics based on 2D images. They also point to the necessity of a thorough physical examination and a thorough assessment of teeth before extraction, the extension of imaging diagnostics by conical CT scan in justified cases, and informing the patient about possible complications. In order to avoid serious complications, the extraction of the concrescent teeth should be performed by an experienced specialist in dental or maxillofacial surgery.
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