CD34-Structure, Functions and Relationship with Cancer Stem Cells.

The CD34 protein was identified almost four decades ago as a biomarker for hematopoietic stem cell progenitors. CD34 expression of these stem cells has been exploited for therapeutic purposes in various hematological disorders. In the last few decades, studies have revealed the presence of CD34 expression on other types of cells with non-hematopoietic origins, such as interstitial cells, endothelial cells, fibrocytes, and muscle satellite cells. Furthermore, CD34 expression may also be found on a variety of cancer stem cells. Nowadays, the molecular functions of this protein have been involved in a variety of cellular functions, such as enhancing proliferation and blocking cell differentiation, enhanced lymphocyte adhesion, and cell morphogenesis. Although a complete understanding of this transmembrane protein, including its developmental origins, its stem cell connections, and other functions, is yet to be achieved. In this paper, we aimed to carry out a systematic analysis of the structure, functions, and relationship with cancer stem cells of CD34 based on the literature overview.

Correlations between Salivary Immuno-Biochemical Markers and HbA1c in Type 2 Diabetes Subjects before and after Dental Extraction.

Dental extraction can trigger certain sequences of complex processes that involve both hard (alveolar bone) and soft tissue (periodontal ligament, gingiva) remodeling. Type 2 diabetes is a serious risk factor for many oral pathologies, both in terms of progression and severity, but also regarding subsequent rehabilitation possibilities. The aim of this study was to establish whether certain molecules: osteoprotegerin (OPG), kappa B nuclear factor receptor activator ligand (RANKL), hepatocyte growth factor (HGF), tumor necrosis factor-α (TNF-α), interleukin 18 (IL-18), matrix metalloproteinase 9 (MMP-9) and oxidative stress markers-total oxidant status (TOS), total antioxidant capacity (TAC)-evaluated in saliva are modified post-extraction in type 2 diabetes mellitus subjects and whether there is a correlation with HbA1c levels. The aforementioned markers plus HbA1c were investigated in a group of systemically healthy subjects (n = 45) and in a type 2 diabetes mellitus group (n = 41) before and three months after a tooth extraction. Diabetes patients' recorded increased levels of OPG, RANKL, TNF-α, MMP-9, IL-18 and TOS compared to controls both pre- and post-extraction. In both study groups, the average OPG, HGF and TAC level recorded an upward trend three months post-extraction. TNF-α registered a statistically significant decrease only in the diabetes group after dental extraction, together with a decrement of mean HbA1c levels in the diabetes group. By plotting the ROC (receiver operating characteristic) curve, at baseline RANKL, TNF-α, IL-18, MMP-9, TOS and OPG were good predictors of HbA1c levels. Post-extraction, there was a significant correlation between HbA1c and oxidative status biomarkers, however the linear regression model indicated the influence of all studied salivary markers in HbA1c determinism, in a considerable proportion. In conclusion, our study demonstrated that several oxidative status markers and proinflammatory biomarkers are modified in the saliva of diabetic patients and they correlate to HbA1c levels, thus being potential indicators of the post-extraction healing status in the oral cavity.

Lower third molar inclusion associated with paraesthesia: A case report.

When lower third molar inclusion is associated with neurosensorial complications, the treatment of choice is its surgical avulsion. One of these complications, that may be the most alarming during a first medical examination, is hemi-lip paraesthesia, that can appear in the presence of several mandibular lesions. This is a report of a rare clinical case in which paraesthesia was linked to the closeness between the root block of the dental element and the mandibular canal, which houses the neurovascular trunk of the lower mandibular nerve. A 64 year-old male Caucasian patient, presented with the chief complaint of past periodic inflammatory events in the retromolar region of the oral cavity and hemi-lip paraesthesia. Upon local clinical and radiological examination, a lower left third molar with class 3 position C inclusion was incriminated. The medical history of the patient revealed well compensated diabetes mellitus type II, and pharmacologically controlled hypertension. The tooth was surgically removed using piezoelectric instruments. Before and after surgery, three types of tests (tactile, pain and thermal sensitivity) were carried out to delimit the area affected by paraesthesia. At 7 days, the area of hypoesthesia of the hemi-lip was significantly reduced. Further improvement in tactile and thermal sensitivity occurred in subsequent follow-up, at 1 and 3 months, postoperatively. This clinical case demonstrates that the surgical intervention performed with piezoelectric instruments prevented the damage of an important structure such as the lower mandibular nerve, and promoted regression of a contingent paraesthesia.

Evaluation of the biocompatibility of resin composite-based dental materials with gingival mesenchymal stromal cells.

Resin composite-based dental materials can leach certain components into the oral environment, causing potentially harmful gingival biological effect. Gingival tissue is a rich source of mesenchymal stem cells (MSCs) that is easily accessible, and can be used as a complementary approach for the investigation of dental material biocompatibility. Using gingival MSCs (gMSCs), the present study aimed to investigate the cytotoxicity of two classes of restorative dental materials (ormocers and resin composites) used to restore class II cavities close to the gingival margin, in addition to analyzing the leached compounds from these resin composite-based materials. Functionality assays (Colony-forming unit, migratory potential, and proliferation assays) and a viability assay (MTT) were employed. Cells' aspect was observed by scanning electron microscopy (SEM). Leached monomers were also quantitated using high-performance liquid chromatography (HPLC). The cytotoxicity of the biomaterials was highlighted by impaired functionality and diminished viability of gMSCs. Despite being variants of the same commercial material, the two ormocers behaved differently one material having a more negative impact on cell functionality than the other. Cells appeared to attach well to all materials. Main monomer molecules were mostly released by the tested materials. For all samples, an increased elution of monomers was recorded in artificial saliva as compared with culture medium. One composite material has released nearly eight times more urethane dimetacrylate in artificial saliva than in culture medium. Significantly lower gMSC viability scores were recorded for all the investigated samples in comparison with the control.

Interaction between a 3D collagen matrix used for periodontal soft tissue regeneration and T-lymphocytes: An in vitro pilot study.

Previous experimental models showed that activation of the immune system, particularly T cells, is required for optimal healing following wounds or surgery in the oral cavity. Therefore, studies to explore the interactions between the immune system and the collagen matrix are mandated. The specific aim of the present study was to analyze the interactions between T lymphocytes and a resorbable three-dimensional (3D) collagen matrix routinely used for soft tissue regeneration during periodontal surgery. Peripheral venous blood samples were collected from five patients. Following Ficoll-Paque separation, mononuclear cells were grown on fully resorbable 3D collagen matrices for 5 days. Lymphocytes were analyzed by flow cytometry for different surface markers, including CD4, CD8, CD38 and CD69. Cell viability and late apoptosis/necrosis were assessed in each group using an apoptosis assay based on Annexin V/propidium iodide staining. After 5 days in contact with the collagen matrix, the T cells expressed different surface markers. The overall T cell population increased significantly in the collagen matrix group compared to the respective controls (31.9±6.5 vs. 38.7±3.8%). CD8 and CD69 also increased significantly compared to their controls (CD69: 19.7±3.0 vs. 27.1±4.5% for collagen vs. control groups). At the same time, CD4 and CD38 expression was similar in both groups. Viability and apoptosis/necrosis were also identical in the samples and controls. These results show that the interaction between the collagen matrix and the immune cells stimulated activation of T cells and did not impair the healing process.

Hepatitis C Infection and Periodontal Disease: Is there a Common Immunological Link?

Hepatitis C virus (HCV) infections could have an important impact on the oral health status of patients, favoring conditions such as periodontal disease and oral cancer. The review of the existing scientific literature written in English was performed, searching for oral and periodontal manifestations of HCV infection and its impact on the oral fluids. HCV infection can determine direct extrahepatic manifestations at the oral and periodontal level including oral lichen planus, Sjögren-like sialadenitis, and oral cancer. The changes caused by the infection in the subjects' immune system, diet, and lifestyle can facilitate the development of oral conditions such as periodontal disease. Important changes also occur in the composition of the infected patients' saliva and gingival fluid. HCV-infected patients need to be carefully monitored in terms of oral health since the infection with the virus can result in oral complications. The cellular and molecular particularities of the gingival fluid of HCV-infected patients can answer some questions regarding its impact upon periodontium impairment and whether this refers to a possible bidirectional relationship, with hepatic biomarker adjustments being induced by the periodontal patients' inflammatory status.

Histology and surface ultrastructure during early healing after gingival augmentation with a three-dimensional collagen matrix: A report of six cases.

OBJECTIVES: The objective of the present case series is to describe the histology and surface ultrastructure of augmented keratinized gingival mucosa in humans during the early healing phase after surgical placement of a xenogeneic collagen matrix. METHOD AND MATERIALS: Six patients underwent surgical augmentation of keratinized tissue by placement of a three-dimensional (3D) xenogeneic collagen matrix. Full-depth mucosal biopsies including original attached gingiva, augmented gingiva, and the separation zone were performed at baseline and at postoperative days 7 and 14. The specimens were stained with hematoxylin-eosin, Masson-trichrome, picrosirius red, and Papanicolaou's trichrome. Low-vacuum scanning electron microscopy (SEM) surface analysis was correlated with histology. RESULTS: The separation zone was clearly visible upon histologic and SEM examination at 7 days. The portions of augmented mucosa consisted of well-structured, immature gingival tissue with characteristics of per secundam healing underlying a completely detached amorphous collagenous membrane-like structure of approximately 100 µm thick. At 14 days, histologic and ultrastructural examinations showed an almost complete maturation process. There were no detectable remnants of the collagen matrix within the newly formed tissues at either time point. CONCLUSIONS: Within their limits the results suggest that the 3D collagen matrix appears to play an indirect role during the early phase of wound healing by protecting the newly formed underlying tissue and guiding the epithelialization process.

Expression of Pentraxin 3 and Thrombospondin 1 in Gingival Crevicular Fluid during Wound Healing after Gingivectomy in Postorthodontic Patients.

Background. Wound healing is a tissue repair process after an injury, and two of its main components are inflammation and angiogenesis, in which course a cascade of mediators is involved. The aim of this research was to evaluate the involvement of Pentraxin 3 and Thrombospondin 1 in wound healing after periodontal surgery (gingivectomy) for gingival overgrowth during orthodontic treatment with or without magnification devices, by assessing their levels in GCF. Methods. From 19 patients with gingival overgrowth as a result of fixed orthodontic treatment, the overgrown gingiva was removed by gingivectomy, from one half of the mandibular arch without magnification and from the other under magnification. Pentraxin 3 and Thrombospondin 1 were determined from gingival crevicular fluid by ELISA tests. Results. Statistically significant differences (p < 0.05) and correlations between levels of the two biomarkers were analyzed. Statistically significant differences were established between levels of the two biomarkers at different time points, with significant positive correlation at the point of 24 hours. Conclusions. Within the limitations of this study, the results seem to sustain the involvement of Pentraxin 3 and Thrombospondin 1 in the processes of inflammation and angiogenesis in wound healing of patients with postorthodontic gingivectomy. The dynamics of Pentraxin 3 and Thrombospondin 1 levels could suggest a reduced inflammation and a faster angiogenesis using microsurgery.

Clinical and histological characterization of an aggressive periodontitis case associated with unusual root canal curvatures.

The article presents the histological and clinical characteristics in a severe generalized aggressive periodontitis case associated with multiple root curvatures and the complex therapeutic approach of the severe periodontal destructions. The patient received a complex therapy, including periodontal non-surgical, regenerative and reconstructive approaches, and also endodontic and prosthetic treatments. Recall appointments were fixed at 3-month intervals. One year after the finalization of the active therapy, a hyperplasic, inflamed interdental papilla associated with a recurrent clinical attachment loss was diagnosed at the mesial aspect of the right maxillary second premolar. A biopsy was harvested for histological examination and the recurrent site was treated. The histological study revealed important modifications of the epithelial layer and of the connective tissue of the gingiva. An extremely accentuated pattern of the gingival rete ridges at the epithelial-connective tissue junction, the presence of inflammatory cells infiltrating the epithelial layer and lamina propria and the disorganization of the fascicules of collagen fibers were observed. The inflammatory infiltrate was dominated by plasma and monocytic-like cells as immunohistochemical analyses highlighted. The complex therapeutic approach led to a satisfactory aesthetic and functional outcome. The severe root curvatures may be an unusual trait in this generalized aggressive periodontitis case substantially increasing the amount and the costs of non-periodontal procedures. In this case, the cell make-up of the inflammatory infiltrate and the paucity of collagen in the infiltrated tissue portions are considered to correspond to a fully developed recurrent lesion.

Salivary and serum biomarkers for the study of side effects of aripiprazole coprescribed with mirtazapine in rats.

The aim of this study was to investigate whether the co-administration of aripiprazole and mirtazapine could determine weight gain and lipid metabolism disorders in Wistar rats, compared to the same side effects produced by mirtazapine alone, and the risk of hepatotoxicity due to the combination of the two substances. Tumor necrosis factor alpha (TNF-α), liver fatty acid binding protein (L-FABP/FABP1) and repulsive guidance molecule C/hemojuvelin (RGM-C/HJV) levels were determined in serum and in saliva. Also, serum levels for total cholesterol (TC), low and high-density lipoprotein (LDL, HDL), triglycerides (TG), aspartate aminotransferase (ASAT) and alanine amino transferase (ALAT) were assessed. We found positive and statistically significant correlations between serum and salivary levels of TNF-α, L-FABP/FABP1 and RGM-C/HJV. Mirtazapine determined significantly differences of TNF-α and L-FABP serum levels; final body weight; TC and LDL levels, leading to higher concentrations than its association with aripiprazole. Although not statistically significant, mirtazapine group experienced higher values for salivary levels of TNF-α, TG and ASAT, and lower values for HDL, compared to aripiprazole + mirtazapine group. The results suggest that aripiprazole might improve some of the disturbances caused by mirtazapine, and that the two drugs combination cause no additional alterations in liver function. Also, the findings indicate that TNF-α, L-FABP/FABP1 and RGM-C/HJV levels can be helpful as biomarkers for metabolic disturbances and impaired function of hepatocytes, and that their salivary determination can replace serum determination.

Silent sinus syndrome--report of a case.

INTRODUCTION: The "silent sinus syndrome" is a rare entity that was first described in 1964 and given this name 30 years later. Although it is well described both from clinically and radiologically point of view we consider that its rarity still makes it a subject for report. CASE PRESENTATION: A 46-year-old patient was admitted for facial asymmetry, diplopia, unilateral left enophthalmos, and inferior displacement of the eye globe, and decreased occlusal pressure in left dentate region. CT scan revealed interior bulging of all left maxillary sinus walls with osteolysis and intense opacification, enlargement of the left middle meatus especially in the posterior part and lateralization of the uncinate process. Nasal endoscopy with 00 rigid scope visualized mild deviation to the right of the nasal septum, enlargement of the left middle meatus by the lateral deviation of the left intersinusal septum and uncinate process. Surgery was scheduled and performed a left maxillary sinus antrostomy. Histopathological examination on the biopsies revealed inflammation. A complete study was performed to assess the elements of inflammation. Postoperative course was simple. Follow-up visit at three and six months, showed significant regression of diplopia and improved facial aspect. CONCLUSIONS: Silent sinus syndrome is a well-defined clinical entity with characteristic imagistic findings. Surgical intervention that restores sinus drainage will interrupt the pathogenesis of the disease and lead to its progressive regression. Topographic associations and density of inflammatory elements analyzed in relation with neoforming vessels suggest their implication in reparatory angiogenesis characteristic to chronic inflammation. Modulating activity in the frame of inflammatory process, of the T-lymphocytes and especially of T-lymphocytes may represent a target for the therapeutic management. Surgery can and should be performed by an endoscopic approach.

Involvement of TSP1 and MMP9/NGAL in angiogenesis during orthodontic periodontal remodeling.

In the present study the aim was to measure the levels of Thrombospondin-1 (TSP1) and Lipocalin-2/matrix metalloproteinase 9 (MMP9/NGAL) complex in gingival crevicular fluid (GCF) at different time points of orthodontic treatment, to determine the relationship between these values and those of total-matrix metalloproteinase 9 (MMP9) and theirs implication in angiogenesis balance, in the situation of a good control of the bacterial plaque, emphasizing the role of TSP1 and MMP9/NGAL complex. GCF samples were collected from 16 young orthodontic patients requiring upper canine distalization (test tooth) with first premolar extraction. The contralateral canine (control tooth) was free from orthodontic force. For the orthodontic appliance, brackets Roth 0.018 inch with 0.012 inch NiTi archwire and a laceback were used. TSP1, MMP9/NGAL, and MMP9 increased from 1 hour before activation of orthodontic appliance to a maximum at 8 hours for MMP9 and 72 hours for MMP9/NGAL and TSP1. The results show a change in time of TSP1, MMP9/NGAL, and MMP9 levels in GCF of patients with this method of orthodontic treatment. The powerful correlation of MMP9/NGAL with TSP1 suggests their stronger involvement in angiogenesis processes in PDL during orthodontic periodontal remodeling, in the situation of a healthy periodontium and a good control of the bacterial plaque.

Extra-genitally located endometriosis.

Endometriosis is defined by the presence of ectopic and endometrial islands outside the uterus. The significance of its finding is also outlined by its less frequent localizations (intestine, gall bladder, lungs) and by its differentiated symptoms complicating the differential diagnosis. The definitive diagnosis can only be reached through a histopathological examination as the detection of this affliction may lead to severe therapeutic errors (radical resection). The importance of an early diagnosis may help in preventing and delaying the effects of this affliction.

Matrix metalloproteinase 9 levels in gingival crevicular fluid in patients after periodontal microsurgery for orthodontic induced gingival hypertrophy.

INTRODUCTION: In this study, we aim to compare the levels of matrix metalloproteinase 9 (MMP9) in the gingival crevicular fluid (GCF), as indicators for healing, in two groups of patients - operated with a classic periodontal surgical technique and the same technique but using a dental microscope. MATERIALS: We included 14 patients with ages between 12 and 26 years, average 14±6.2 years. Eight patients were women and six men. All patients presented gingival hypertrophy because of the orthodontic treatment on the mandibular arch. We performed gingivectomy on one-half of the mandibular arch by classic periodontal surgery and on the other half of the mandibular arch by a microscope-assisted gingivectomy. METHODS: In the hypertrophied gingiva, the expression of MMP9 was identified using immunohistochemical-staining techniques. For immunological determination of MMP9 in GCF we performed Elisa tests. RESULTS: We found different levels in different moments of the healing process for the two hemiarcades. CONCLUSIONS: We consider that faster healing in case of microscope-assisted gingivectomy may be related to the expression of MMP-9 in the GCF.

The study of E-cadherine and CD44 immunoexpression in oral squamous cell carcinoma.

In spite of the progresses achieved in surgical treatment, radiotherapy and chemotherapy, the survival rate in oral squamous cell carcinoma (OSCC) remain unchanged among past three decades, which made this neoplasia a major problem of health in the entire world. There were investigated 42 cases of OSCC with different sites and various grades of differentiation, by histological and immunohistochemical techniques (by LSAB/HRP method), using E-cadherine and CD44. Considering the differentiation grade, the cases were histopathologically classified as 9 cases of well-differentiated squamous carcinoma, 14 cases of moderately differentiated squamous carcinoma, and 19 cases of poorly differentiated squamous carcinoma. The E-cadherine immunoexpression study indicated an immunostaining degree 3 in well-differentiated squamous carcinoma, 2 in moderately differentiated squamous carcinoma, and 1 in poorly differentiated squamous carcinoma. The results of CD44 immunostaining indicated in most of the cases an immunostaining degree 2, especially in moderately differentiated OSCC. The immunostaining degree 3 corresponded to nine cases of well-differentiated OSCC, and other two cases of moderately differentiated OSCC. Immunostaining degree 1 corresponded to poorly differentiated OSCC. The results indicate the possibility of using the two-immunohistochemical markers as prognostic factors in OSCC.

Clinico-imaging and anatomopathologic correlations in sarcomas of maxilla.

Sarcomas are relatively uncommon tumors, accounting for 1% of all malignancies. Sarcomas are commonly classified according to their site of origin: soft tissues or bone. The purpose of the clinic study was to focus the symptoms and the clinic signs. The radio-imaging study is essential in the evaluation of the maxilla tumors. The histopathologic study was done to determine the histological type, the differentiation level, the invasion level as well as the presence or absence of the metastases in drainage ganglia. The correlation of the findings of this study leads to a clear and correct clinic diagnosis, an adequate local or general therapy and a prognostic. The diagnostic role of imaging is essential and often permits the orientation to benignity or, on the contrary, requires biopsy if the image is an aggressive one or of uncertain nature. Advances in diagnostic imaging have contributed substantially to the management of tumors. The strong collaboration among the physician, imaging personnel and anatomo-pathologist serves the patient's benefit.