Two novel direct SPIO labels and in vivo MRI detection of labeled cells after acute myocardial infarct.

BACKGROUND: Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide. Cellular decay due hypoxia requires rapid and validated methods for possible therapeutic cell transplantation. PURPOSE: To develop direct and rapid superparamagnetic iron oxide (SPIO) cell label for a large-animal model and to assess in vivo cell targeting by magnetic resonance imaging (MRI) in an experimental AMI model. MATERIAL AND METHODS: Bone marrow mononuclear cells (BMMNCs) were labeled with SPIO particles using two novel direct labeling methods (rotating incubation method and electroporation). Labeling, iron incorporation in cells and label distribution, cellular viability, and proliferation were validated in vitro. An AMI porcine model was used to evaluate the direct labeling method (rotating incubation method) by examining targeting of labeled BMMNCs using MRI and histology. RESULTS: Labeling (1 h) did not alter either cellular differentiation potential or viability of cells in vitro. Cellular relaxation values at 9.4 T correlated with label concentration and MRI at 1.5 T showing 89 ± 4% signal reduction compared with non-labeled cells in vitro. In vivo, a high spatial correlation between MRI and histology was observed. The extent of macroscopic pathological myocardial changes (hemorrhage) correlated with altered function detected on MRI. CONCLUSION: We demonstrated two novel direct SPIO labeling methods and demonstrated the feasibility of clinical MRI for monitoring targeting of the labeled cells in animal models of AMI.

Competing risks analysis of cause-specific mortality in patients with oral squamous cell carcinoma.

BACKGROUND: Survival studies on head and neck cancers are frequently reported with inadequate account for competing causes of death. Realistic descriptions and predictions of postdiagnosis mortality should be based on proper competing risks methodology. METHODS: Prognosis of patients with oral squamous cell carcinoma (OSCC) in terms of mortality from OSCC and from other causes, respectively, was analyzed according to recent methodological recommendations using cumulative incidence functions and models for cause-specific hazards and subdistribution hazards in 306 patients treated in a tertiary care center in Northern Finland. RESULTS: More coherent and informative descriptions and predictions of mortality by cause were obtained with state-of-the-art statistical methods for competing risks than using the prevalent but questionable practice to graph "disease-specific survival." CONCLUSION: From the patients' perspective, proper competing risks analysis offers more relevant prognostic scenarios than naïve analyses of "disease-specific survival"; therefore, it should be used in prognostic studies of head and neck cancers. © 2016 Wiley Periodicals, Head Neck 39: 56-62, 2017.

Matrix metalloproteinase-8 regulates transforming growth factor-ß1 levels in mouse tongue wounds and fibroblasts in vitro.

Matrix metalloproteinase-8 (MMP-8)-deficient mice (Mmp8-/-) exhibit delayed dermal wound healing, but also partly contradicting results have been reported. Using the Mmp8-/- mice we investigated the role of MMP-8 in acute wound healing of the mobile tongue, and analyzed the function of tongue fibroblasts in vitro. Interestingly, in the early phase the tongue wounds of Mmp8-/- mice healed faster than those of wild type (wt) mice resulting in significant difference in wound widths (P=0.001, 6-24h). The Mmp8-/- wounds showed no change in myeloperoxidase positive myeloid cell count, but the level of transforming growth factor (TGF)-ß1 was significantly increased (P=0.007) compared to the wt tongues. Fibroblasts cultured from wt tongues expressed MMP-8 and TGF-ß1. However, higher TGF-ß1 levels were detected in Mmp8-/- fibroblasts, and MMP-8 treatment decreased phosphorylated Smad-2 levels and α-smooth muscle actin expression in these fibroblasts suggesting reduced TGF-ß1 signaling. Consistently, a degradation of recombinant TGF-ß1 by MMP-8 decreased its ability to activate the signaling cascade in fibroblasts. Moreover, collagen gels with Mmp8-/- fibroblasts reduced more in size. We conclude that MMP-8 regulates tongue wound contraction rate and TGF-ß1 levels. In vitro analyses suggest that MMP-8 may also play a role in regulating TGF-ß1 signaling of stromal fibroblasts.

Outcome of treatment of implant-retained overdenture in patients with extreme mandibular bone resorption treated with bone grafts using a modified tent pole technique.

PURPOSE: To evaluate the outcome (prosthetic maintenance, survival of implants, patient satisfaction, and quality of life) of prosthetic treatment using an implant-retained overdenture and a modified tent pole procedure for severe mandibular resorption. MATERIAL AND METHODS: Seventeen edentulous patients (mean age, 68 yr; range, 54 to 77 yr) with severely resorbed mandibles were treated with autogenous bone grafts using a modified tent pole technique and implant overdentures. A bar was used to splint the implants and the final prostheses with implant connection were completed approximately 7 months after surgery. The mean follow-up time was 5 years (1.5 to 7.4 yr). Patients filled out the Oral Health Impact Profile-14 questionnaire concerning their oral health-related quality of life, and then panoramic radiographs were taken during clinical examination. RESULTS: The stability of the overdenture was good in 58.8% of cases and retention was good in 64.7%. The most usual prosthetic complication was loosening of the attachment component, which occurred in 7 cases (41.2%). The amount of plaque and bleeding was more remarkable on the lingual surface of the implants and less remarkable on the buccal surface. Pocket depth around the implants seemed to correspond to intraoral implantation. The radiographs depicted excellent grafted bone survival. The patients' oral health-related quality of life was found to be good after treatment. CONCLUSIONS: Implant placement with bone grafting using a modified tent pole technique enables the achievement of a good prosthetic solution and the rehabilitation of occlusion, thereby improving the functionality of the prostheses and quality of life.

Navigation-assisted Le Fort I osteotomy with midpalatal split to treat compressive pathologies of the craniovertebral junction.

This report describes the management of the case of an 11-year-old girl with serious compressive pathology of the craniocervical junction using a navigation-guided Le Fort I level maxillotomy and midline split. In this pediatric case, image guidance significantly enhanced intraoperative orientation and helped to determine the correct location of the horizontal osteotomy lines at the Le Fort I level.

Tent-pole approach to treat severely atrophic fractured mandibles using immediate or delayed protocols: preliminary case series.

PURPOSE: To investigate the outcomes of patients with severely resorbed fractured mandibles who were managed with a modified tent-pole procedure. PATIENTS AND METHODS: Four edentulous patients (2 male and 2 female; mean age, 59.5 years; range, 52 to 64 years) with a severely atrophic fractured mandible and less than 10 mm of vertical height of the body of the mandible were treated with an immediate or a delayed protocol (n=2 in each group). In the immediate group, a transcutaneous submental approach was used to provide open reduction with rigid fixation, immediate dental implant placement in the anterior mandible, and an autogenous particulate iliac bone grafting harvested from the posterior iliac crest. In the delayed protocol group, the fractures were treated with an open reduction and rigid fixation. Six months after fracture treatment, the fixation hardware was removed and a tent-pole approach was used to place the dental implants to the anterior mandible with an autogenous bone graft harvested from the posterior iliac crest. Implant fixtures were loaded at 3 months as the patients were fitted with healing caps, and the dental implants were loaded using provisional screw-retained acrylic resin prostheses and bar-retained overdentures afterward. The mean follow-up was 19.8 months (range, 13 to 28 months). RESULTS: The postoperative course and healing of the 4 patients was uneventful, without any fracture nonunion. The average alveolar augmentation±standard deviation was 7.5±1.17 mm (range, 6.6 to 9.0 mm). There was no bone resorption around any of the endosseous implants on follow-up. All 4 patients wore their dental implant-supported prosthesis comfortably. CONCLUSIONS: This preliminary evidence indicates that the modified tent-pole technique may be a safe and effective method to manage the fractured severely resorbed mandible using an immediate or a delayed protocol. Much larger-scale prospective evidence is required to further validate this observation.

Long-term follow-up of severely resorbed mandibles reconstructed using tent pole technique without platelet-rich plasma.

PURPOSE: To investigate the results of edentulous patients with severely resorbed mandibles who were treated with a modified tent pole procedure. PATIENTS AND METHODS: Twenty-two edentulous patients (3 men, 19 women; mean age, 62 yr; range, 51 to 72 yr) with a history of conservative prosthodontic treatment failures were included this study. Using a transcutaneous submental approach, 4 endosseous dental implants were placed in the anterior mandible of each patient and covered with autogenous bone grafts harvested from the posterior iliac crest without the addition of platelet-rich plasma. Follow-up ranged from 3 to 9 years. RESULTS: The postoperative course of the patients was uneventful, without any surgical infections. At 3 months postoperatively, the density of the grafted bone appeared to closely resemble that of the surrounding alveolar bone on panoramic radiographs. The average alveolar augmentation was 6.3 mm (standard deviation, 1.59 mm; range, 4 to 10 mm) and long-term follow-up showed no bone resorption around the endosseous implants. CONCLUSIONS: The modified tent pole technique without the addition of platelet-rich plasma is a safe and effective method to reconstruct the severely resorbed mandible.

Expression of matrix metalloproteinases-2, -8, -13, -26, and tissue inhibitors of metalloproteinase-1 in human osteosarcoma.

Osteosarcoma (OS) is among most common malignant tumour of bone. Matrix metalloproteinases (MMPs) are predominantly associated with poor prognosis of several cancers, although some of them, like MMP-8, seem to have a protective role in some cancers. We analyzed the distribution patterns of MMP-2, -8, -13, -26, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in 25 OS patients. MMP-2, -8, -13, -26 and TIMP-1 were mostly detected in sarcoma cells. Response to chemotherapy affected the amount of MMP-2, -8, and -13 in resection sections when compared to biopsies: patients with excellent or good response had less positivity to MMP-2 in chemotherapy samples than those with moderate or poor response. We conclude that MMP-2, -8, -13, -26, and TIMP-1 are expressed in OS tissue, and all, except protective MMP-8, were also found in metastases indicating that MMPs and TIMP-1 can participate in the OS progression.

Healing of extraction sockets in collagenase-2 (matrix metalloproteinase-8)-deficient mice.

Matrix metalloproteinase-8 (MMP-8) participates in skin wound healing and inflammation. We hypothesized that MMP-8 plays a role in wound healing after tooth extraction and in periapical inflammation. Bone formation, collagen metabolism, and inflammation in tooth extraction socket and in periapical lesions were analyzed in wild-type mice and in MMP-8-deficient (MMP-8(-/-)) mice. New trabecular bone area in the extraction sockets and in periapical lesions were similar in both groups. In extraction sockets significantly more type III procollagen was synthesized, and the neutrophil and MMP-9 levels were lower in MMP-8(-/-) mice. The amount of Fas ligand, identified as a substrate for MMP-8, was lower in alveolar mucosa but higher in alveolar bone of MMP-8(-/-) mice. These results indicate that MMP-8 can modulate inflammation and collagen metabolism of alveolar bone and mucosa.

Collagenase-2 (MMP-8) and matrilysin-2 (MMP-26) expression in human wounds of different etiologies.

Wound healing involves highly controlled events including reepithelialization, neoangiogenesis, and reformation of the stromal compartment. Matrix metalloproteinases (MMPs) are a family of neutral zinc-dependent endopeptidases known to be essential for the wound-healing process. MMP-8 (collagenase-2) is a neutrophil-derived highly effective type I collagenase, recently indicated to be important for acute wound healing. MMP-26 is a more recent and less well-studied member of the MMP family. Our aim was to study the expression of MMP-8 and MMP-26 in human cutaneous wound repair and chronic wounds using histological methods and cell culture. MMP-8 expression was associated with epithelial cells, neutrophils, and other inflammatory cells in chronic human wounds. MMP-26 was prominently expressed in the extracellular compartment of most chronic wounds in close vicinity to the basement membrane area. MMP-26 was also expressed in acute day 1 wounds with declining expression thereafter. In vitro wound experiments showed that both MMP-8 and MMP-26 were expressed by migrating human mucosal keratinocytes. Inhibiting MMP-26 resulted in aberrant keratinocyte migration and proliferation. We conclude that MMP-8 and MMP-26 are differentially expressed in acute and chronic wounds.