Giovanna Murmura

Vascular Endothelial Growth Factor (VEGF), Mast Cells and Inflammation

Vascular endothelial growth factor (VEGF) is one of the most important inducers of angiogenesis, therefore blocking angiogenesis has led to great promise in the treatment of various cancers and inflammatory diseases. VEGF, expressed in response to soluble mediators such as cytokines and growth factors, is important in the physiological development of blood vessels as well as development of vessels in tumors. In cancer patients VEGF levels are increased, and the expression of VEGF is associated with poor prognosis in diseases. VEGF is a mediator of angiogenesis and inflammation which are closely integrated processes in a number of physiological and pathological conditions including obesity, psoriasis, autoimmune diseases and tumor. Mast cells can be activated by anti-IgE to release potent mediators of inflammation and can also respond to bacterial or viral antigens, cytokines, growth factors and hormones, leading to differential release of distinct mediators without degranulation. Substance P strongly induces VEGF in mast cells, and IL-33 contributes to the stimulation and release of VEGF in human mast cells in a dose-dependent manner and acts synergistically in combination with Substance P. Here we report a strong link between VEGF and mast cells and we depict their role in inflammation and immunity.

Vertical ridge augmentation of atrophic posterior mandible using an inlay technique with a xenograft without miniscrews and miniplates: case series

BACKGROUND Rehabilitation of partially or totally edentulous posterior mandible with implant-supported prosthesis has become a common practice in the last few decades, with reliable long-term results. The use of miniscrews and miniplates have been reported to increase the risk of fracture of the osteotomy segments. The purpose of this case series was to use an inlay technique, without the use of miniscrews and miniplates for stabilization of the transported bone fragments. MATERIALS AND METHODS Nine consecutive patients (six men and three women) aged between 26 and 51 years (mean 44 years) were enrolled in this study. A horizontal osteotomy was performed 2-3 mm above the mandibular canal, and two oblique cuts were made using a piezosurgery device. The final phase of the osteotomy was performed with chisels. The osteotomized segment was then raised in the coronal direction, sparing the lingual periosteum. Two miniblocks of xenograft without miniscrews and miniplates were inserted mesially and distally between the cranial osteotomized segment and the mandibular basal bone. The residual space was filled with particles of cortico-cancellous porcine bone. Four months after surgery, a panoramic X-ray was taken before implant insertion. A bone trephine with an internal diameter of 2 mm was used as the second dental drill to take a bone core biopsy during preparation of the #35 and #37 or #45 and #47 implant sites. RESULTS The postoperative course was uneventful in seven of the nine patients. No dehiscence of the mucosa was observed at the marginal ridge of the mobilized fragment. Newly formed bone was present near the osteotomized segments, and was observed in the bottom half of the specimens and was identified by its higher affinity toward the staining. Newly formed bone was observed to be in close contact with the particles of biomaterials. No gaps or connective tissue were present at the bone-biomaterial interface. Histomorphometry demonstrated that 44±2.1% of the specimens was composed by newly formed bone, 18±0.8% by marrow spaces, and 33±2.4% by the residual grafted biomaterial. CONCLUSION The rigidity of the equine collagenated block allowed to eliminate the use of miniscrews and miniplates and simplified the technique. Moreover, the rigidity of the block allowed maintenance of the space.

In vitro evaluation of fracture resistance and failure mode of internally restored endodontically treated maxillary incisors with differing heights of residual dentin

STATEMENT OF PROBLEM Some of the associated effects of different restorative systems placed in endodontically treated teeth with varying heights of residual dentin have yet to be examined in a comprehensive manner. There is a need for additional information regarding fracture resistance and mode of failure. PURPOSE The purpose of this in vitro study was to evaluate the effect of 3 different restorative techniques with varying amounts of remaining dentin heights on the fracture resistance and failure mode of endodontically treated teeth. MATERIAL AND METHODS Three groups of 40 human maxillary incisors were subdivided into 4 subgroups (n=10) with respect to the uniform height of the residual coronal dentin, defined as 0-, 2-, 4-, or 5-mm from the cemento-enamel junction, and then restored internally using a composite resin (Z100 MP) (control group), a cobalt-chromium ceramic alloy custom-made cast post and core (IPS d.SIGN 30; CCPC group), or a carbon fiber post system (Tech Xop 2000; CFP group). All specimens were then restored with nonprecious cast crowns. Static loading tests were performed on each specimen until failure (crack without a complete fracture). The data were analyzed with 2-way ANOVA and Bonferroni-corrected t test for independent samples (alpha=.05). Failure was classified as either favorable (allowing repair) or catastrophic (not allowing repair). RESULTS The fracture resistance values (N) for the 0-, 2-, 4-, and 5-mm residual dentin heights were: 88, 143, 154, and 202 for the control group, 230, 264, 364, and 383 for the CCPC group, and 153, 235, 346, and 357 for the CFP group, respectively. Generally, all the differences tested were statistically significant. The failure mode was catastrophic for no control specimens, for 36 CCPC specimens, and for 4 CFP specimens. CONCLUSIONS The highest and lowest fracture resistances were recorded for the CCPC and control groups, respectively, at each residual dentin height. An increased height of residual dentin generally provided greater fracture resistance. The fracture resistance of the CCPC group was, however, similar or only slightly higher than that of the CFP group when 2, 4, or 5 mm of residual dentin height was present. In contrast, the failure mode was favorable for almost all of the CFP and control groups, while it was catastrophic in most of the CCPC group.

Impact of mast cells on the skin.

When through the skin a foreign antigen enters it provokes an immune response and inflammatory reaction. Mast cells are located around small vessels that are involved in vasaldilation. They mature under the influence of local tissue to various cytokines. Human skin mast cells play an essential role in diverse physiological and pathological processes and mediate immediate hypersensitive reaction and allergic diseases. Injection of anti-IgE in the skin or other agents that directly activate mast cells may cause the decrease in vascular tone, leakage of plasma and may lead to a fall in blood pressure with fatal anaphylactic shock. Skin mast cells are also implicated as effector cells in response to multiple parasites such as Leishmania which is primarily characterized by its tissue cutaneous tropism. Activated macrophages by IFNγ, cytotoxic T cells, activated mast cells and several cytokines are involved in the elimination of the parasites and immunoprotection. IL-33 is one of the latest cytokines involved in IgE-induced anaphylaxis and in the pathogenesis of allergic skin disorders. IL-33 has been shown in epidermis of patients with psoriasis and its skin expression causes atopic dermatitis and it is crucial for the development of this disease. Here we review the impact of mast cells on the skin.

Impact of Capsaicin on Mast Cell Inflammation

Mast cells are inflammatory cells, and they are prominent in inflammatory diseases such as allergy and asthma. Mast cells possess high-affinity receptors for IgE (FCεRI) and the cross-linking of these receptors is essential to trigger the secretion of granules containing arachidonic acid metabolism [such as prostaglandin (PG) D2, leukotriene (LT) B4, and LTC4], histamine, cytokines, chemokines, and proteases, including mast cell-specific chymases and tryptases. Activation of mast cells provokes the secretion of cytokines and mediators that are responsible for the pathologic reaction of immediate hypersensitivity. Sensory nerve stimulation by irritants and other inflammatory mediators provokes the release of neuropeptides, causing an increase in vascular permeability, plasma extravasation and edema. Trigeminal nerve stimulation actives dura mast cells and increases vascular permeability, effects inhibited by capsaicin. Capsaicin causes release of sensory neuropeptide, catecholamines and vasodilation. Several studies have reported that capsaicin is effective in relief and prevention of migraine headaches, improves digestion, helps to prevent heart disease, and lowers blood cholesterol and blood pressure levels. The findings reported in these studies may have implications for the pathophysiology and possible therapy of neuroinflammatory disorders.

IL-36 Receptor Antagonist with Special Emphasis on IL-38:

IL-36 is another family member of IL-1 and induces the production of proinflammatory cytokines and activates MAPK and NFκB pathways. IL-36 is a common mediator of innate and adaptive immune response and is inhibited by IL-36 receptor antagonist (RA). IL-36RA acts on IL-36 receptor ligand which exerts proinflammatory effect in vivo and in vitro. IL-38 binds to IL-36 receptor as does IL-36RA and has similar biological effects on immune cells. IL-38 is also a member of IL-1 cytokine and shares some characteristics of IL-1RA, binding the same IL-1 receptor type I. IL-38 plays a role in the pathogenesis of inflammatory diseases, exerting protective effect in some autoimmune diseases. Both IL-38 and IL-36RA have an anti-inflammatory biological effect, however in some cases have contrary effects.

Delayed expansion of the atrophic mandible by ultrasonic surgery: a clinical and histologic case series.

PURPOSE Ridge expansion is used to widen narrow ridges with adequate height for implant placement. This human case series presents the clinical and histologic results of delayed expansion of mandibles by ultrasonic surgery. MATERIALS AND METHODS Patients with residual alveolar ridge width between 2.3 and 4.1 mm in the coronal area of the posterior mandible were included in the study. First, four linear corticotomies were carried out by ultrasonic surgical device. Four weeks later, adequate bone expansion with a combination of scalpels, thin chisels, and threaded osteotomes that did not compromise cortical vascularization was performed, and two implants per ridge were inserted. Any gaps were filled with corticospongious porcine biomaterial. Three months after implant placement, healing caps were inserted, and bone cores were harvested from the regenerated areas for histologic analysis. Crestal width was recorded at each surgery. RESULTS The postoperative course was uneventful in all 32 patients (64 implants) who took part in the study, and the implant success rate was 96.88% at 3 months. The mean increase in ridge width was 5.17 ± 0.86 mm. The histologic specimens showed a mixture of new bone and particles of biomaterial, as well as newly formed bone. Histomorphometry demonstrated that 64% ± 3.1% of the specimen was composed of newly formed bone, 8% ± 0.8% was made up of marrow spaces, and 27% ± 2.6% comprised the residual grafted biomaterial. CONCLUSION This study showed that mandibular ridge expansion using a delayed split-crest technique by means of ultrasonic surgery and association with biomaterial led to good horizontal bone gain, with no fractures of the buccal plate, and a high implant success rate. The histologic specimens showed newly formed bone and good integration of the biomaterial.

Hemostasis control in dental extractions in patients receiving oral anticoagulant therapy: an approach with calcium sulfate.

AbstractThe aim of this study was to evaluate the use of calcium sulfate (CaS) as a hemostatic agent after tooth extraction in patients with anticoagulant drug therapy.A total of 30 patients undergoing anticoagulant therapy (22 women and 8 men) with a mean age of 54.6 years (SD = 9.2 years), needing dental extractions, were selected for this study. They were divided into 2 groups, control (group 1) and test (group 2), in a randomized way. In group 1 patients, the postextraction socket was managed with obliterative suture only. Group 2 patients were treated with CaS placed into the postextraction sockets. All the patients did not interrupt the anticoagulant therapy during the dental treatment.The healing pattern was found to be approximately similar in all treatment groups, showing significant improvement at each consecutive visit. However, a statistically significant difference in the adequate hemostasis was evident between groups 1 and 2 (P = 0.0056).The use of CaS helped to control the bleeding from inside the socket, producing instantly a very good hemostasis. Further studies are necessary to confirm the simplicity, possibilities, and limits of the proposed procedure.

Effect of Nanoscale Topography of Titanium Implants on Bone Vessel Network, Osteocytes, and Mineral Densities

BACKGROUND Chemical and physical properties of an implant surface have a major influence on the structure of peri-implant bone and thus may influence the clinical performance of the implant. This study aims to evaluate the bone microstructure around implants with and without added nanometer-sized calcium phosphate particles. METHODS An implant with dual acid-etched surface (control) and an implant with dual acid-etched surface and CaP nanoparticles (test) were placed in the posterior maxilla of 15 patients. Bone microstructure was evaluated for osteocyte density (OD), bone vessel volume density (BVVD), and bone mineral density (BMD). RESULTS BVVD was 1.806 ± 0.05 for test implants and 1.533 ± 0.10 for control implants (P <0.001). BMDlow was 17.4 × 10(4) µm(2) for test implants and 15.0 × 10(4) µm(2) for control implants (P = 0.025). Results from the BMDhigh comparison, test versus control, were not statistically significant (P >0.05). OD was 575.6 ± 63.7 mm(2) for test implants and 471.2 ± 61.9 mm(2) for control implants (P <0.001). CONCLUSIONS After 8 weeks of healing, the bone microstructure around test implants appeared to be significantly more organized. Clinical implications of these results include shortened healing time and indication for earlier loading protocols.

Expansion of the alveolar bone crest with ultrasonic surgery device: clinical study in mandible.

The purpose of this paper was to document the application to the split-crest mandibular procedure in two stage in order to avoid cortical resorption due to periosteal detachment in buccal cortical bone of the alveolar crest. Twenty-two healthy patients with non-contributory past medical history (14 women and 8 men, all non-smokers, mean age 59 years, range 54–65 years) were included in this study. After buccal mucoperiosteal flap was followed by a sagittal corticotomy in the coronal area of the alveolar crest and a second sagittal corticotomy, but in a lower (basal) position and two vertical corticotomies in the buccal wall, using a ultrasonic surgery device (Surgysonic, Esacrom, Imola Italy). Adequate crest expansion was achieved without compromising cortical vascularisation by utilising a combination of scalpel, thin chisels and threaded osteotomes (Bone System, Milano, Italy). Postoperative results were assessed by panoramic and periapical radiographs. Ossification of the osteotomy lines was evident and could be observed as sites with increasing radiopacity on panoramic and periapical radiographs 3 months after implants insertion. No dehiscence of the mucosa was observed. No patient suffered from hypoaesthesia. The mean horizontal bone increase in coronal area was 5±3 mm. Mandibular ridge expansion using a split-crest technique that included grafting the implant sites with a ultrasonic surgery device is a viable therapeutic alternative for implant placement in this patient population.