Does new bone formation vary in different sites within the same maxillary sinus after lateral augmentation? A prospective histomorphometric study.

OBJECTIVE: The aim of this study was to evaluate histomorphometric outcomes of lateral maxillary sinus augmentation in different areas of the same cavity and to correlate results to bucco-palatal sinus width (SW) and residual bone height (RBH). MATERIAL AND METHODS: Patients needing maxillary sinus floor elevation (RBH <5 mm) to insert two nonadjacent implants were treated with lateral augmentation using a composite graft. Six months later, two bone-core biopsies (mesial/distal) were retrieved in implant insertion sites. SW and RBH were measured on cone beam computed tomography, and correlations between histomorphometric and anatomical parameters were evaluated by multivariate linear regression analysis. RESULTS: Twenty patients underwent sinus augmentation, and eighteen were included in the final analysis (two dropouts for membrane perforation). Mean newly formed mineralized tissue percentage (%NFMT) after 6 months in mesial and distal sites was 17.5 ± 4.7 and 11.6 ± 4.7, respectively (p = .0004). Multivariate linear regression showed a strong negative correlation between SW and %NFMT (ß coefficient=-.774, p < .0001) and no correlation between RBH and %NFMT (ß coefficient =-.038, p = .825). CONCLUSIONS: The present study confirms that %NFMT after lateral sinus augmentation occurs at different rates in different anatomical areas of the same maxillary sinus, showing a strong negative correlation with SW, whereas no influence of RBH was observed. Clinicians should regard SW as a guide for graft selection and to decide duration of the healing period. Researchers should consider SW as a predictor variable, when comparing regenerative outcomes of different biomaterials by using maxillary sinus as an experimental model.

Pregnancy, oral health and dental education: an overview on the northeast of Italy.

Objectives To evaluate the level of knowledge of pregnant women and puerpers about oral health and prevention during and after gestation. Methods One hundred women aged 18-49 years (mean age 33±6 years) were included in this cross-sectional study. An anonymous questionnaire with 24 items related to oral health has been administered during or just after pregnancy. Firstly, answers have been analyzed on the full population and then subdividing the sample on the base of age ranges (G1: 18-25 years, G2: 26-35 years and G3: >35 years) and number of pregnancies (FP: first pregnancy; SP: second or more pregnancies). Parametric tests have been chosen for the statistical analysis; in particular, Anova test for independent samples was used to evaluate differences of baseline demographic characteristics among subgroups G1, G2, G3 while chi-square test was used for FP and SP subgroups. Anova test was also used to intercept differences on answers given to the questionnaire among G1, G2 and G3 group; for FP and SP group was used t-test. Results Level of information and knowledge of the full sample was medium-low and no significant differences have been observed between groups regarding awareness of the own level of the oral hygiene and knowledge of oral care. Conclusions Results of this survey underline the high necessity of educational programs regarding oral care in pregnant and puerpers women. A strict collaboration between medical figures (dentist, oral hygienist, gynecologist and obstetric) is strongly encouraged to spread the concept of prevention.

The isoprenoid end product N6-isopentenyladenosine reduces inflammatory response through the inhibition of the NFκB and STAT3 pathways in cystic fibrosis cells.

OBJECTIVE: N6-isopentenyladenosine (iPA) is an intermediate of the mevalonate pathway that exhibits various anti-cancer effects. However, studies on its anti-inflammatory activity are scarce and underlying molecular mechanisms are unknown. Therefore, we aimed to investigate the ability of iPA to exert anti-inflammatory effects in the human cystic fibrosis (CF) cell model of exacerbated inflammation. MATERIALS AND METHODS: TNFα-stimulated CF cells CuFi-1 and its normal counterpart NuLi-1 were pre-treated with increasing concentrations of iPA and cell viability and proliferation were assessed by MTT and BrdU assays. The effect of iPA on IL-8 and RANTES secretion was determined by ELISA, and the activation and expression of signaling molecules and selenoproteins were studied by Western blot. To assess the direct effect of iPA on NFκB activity, luciferase assay was performed on TNFα-stimulated HEK293/T cells transfected with a NFκB reporter plasmid. RESULTS: We demonstrated for the first time that iPA prevents IL-8 and RANTES release in TNFα-stimulated CF cells and this effect is mediated by increasing the expression of the direct NFκB inhibitor IκBα and decreasing the levels of STAT3. Consistent with this, we showed that iPA inhibited TNFα-mediated NFκB activation in HEK/293T cells. Finally, we also found that iPA improved the levels of glutathione peroxidase 1 and thioredoxin reductase 1 only in CF cells suggesting its ability to maintain sufficient expression of these anti-oxidant selenoproteins. CONCLUSIONS: Our findings indicate that iPA can exert anti-inflammatory activity especially in the cases of excessive inflammatory response as in CF.

BAG3 is involved in neuronal differentiation and migration.

Bcl2-associated athanogene 3 (BAG3) protein belongs to the family of co-chaperones interacting with several heat shock proteins. It plays a key role in protein quality control and mediates the clearance of misfolded proteins. Little is known about the expression and cellular localization of BAG3 during nervous system development and differentiation. Therefore, we analyze the subcellular distribution and expression of BAG3 in nerve-growth-factor-induced neurite outgrowth in PC12 cells and in developing and adult cortex of mouse brain. In differentiated PC12 cells, BAG3 was localized mainly in the neuritic domain rather than the cell body, whereas in control cells, it appeared to be confined to the cytoplasm near the nuclear membrane. Interestingly, the change of BAG3 localization during neuronal differentiation was associated only with a slight increase in total BAG3 expression. These data were coroborated by transmission electron microscopy showing that BAG3 was confined mainly within large dense-core vesicles of the axon in differentiated PC12 cells. In mouse developing cortex, BAG3 appeared to be intensely expressed in cellular processes of migrating cells, whereas in adult brain, a diffuse expression of low to medium intensity was detected in neuronal cell bodies. These findings suggest that BAG3 expression is required for neuronal differentiation and migration and that its role is linked to a change in its distribution pattern rather than to an increase in its protein expression levels.

The molecular characterization of a depurinated trial DNA sample can be a model to understand the reliability of the results in forensic genetics.

The role of DNA damage in PCR processivity/fidelity is a relevant topic in molecular investigation of aged/forensic samples. In order to reproduce one of the most common lesions occurring in postmortem tissues, a new protocol based on aqueous hydrolysis of the DNA was developed in vitro. Twenty-five forensic laboratories were then provided with 3.0 µg of a trial sample (TS) exhibiting, in mean, the loss of 1 base of 20, and a molecular weight below 300 bp. Each participating laboratory could freely choose any combination of methods, leading to the quantification and to the definition of the STR profile of the TS, through the documentation of each step of the analytical approaches selected. The results of the TS quantification by qPCR showed significant differences in the amount of DNA recorded by the participating laboratories using different commercial kits. These data show that only DNA quantification "relative" to the used kit (probe) is possible, being the "absolute" amount of DNA inversely related to the length of the target region (r(2) = 0.891). In addition, our results indicate that the absence of a shared stable and certified reference quantitative standard is also likely involved. STR profiling was carried out selecting five different commercial kits and amplifying the TS for a total number of 212 multiplex PCRs, thus representing an interesting overview of the different analytical protocols used by the participating laboratories. Nine laboratories decided to characterize the TS using a single kit, with a number of amplifications varying from 2 to 12, obtaining only partial STR profiles. Most of the participants determined partial or full profiles using a combination of two or more kits, and a number of amplifications varying from 2 to 27. The performance of each laboratory was described in terms of number of correctly characterized loci, dropped-out markers, unreliable genotypes, and incorrect results. The incidence of unreliable and incorrect genotypes was found to be higher for participants carrying out a limited number of amplifications, insufficient to define the correct genotypes from damaged DNA samples such as the TS. Finally, from a dataset containing about 4500 amplicons, the frequency of PCR artifacts (allele dropout, allele drop-in, and allelic imbalance) was calculated for each kit showing that the new chemistry of the kits is not able to overcome the concern of template-related factors. The results of this collaborative exercise emphasize the advantages of using a standardized degraded DNA sample in the definition of which analytical parameters are critical for the outcome of the STR profiles.

Chairside CAD/CAM Materials: Current Trends of Clinical Uses.

Restorative materials are experiencing an extensive upgrade thanks to the use of chairside Computer-aided design/computer-assisted manufacturing (CAD/CAM) restorations. Therefore, due to the variety offered in the market, choosing the best material could be puzzling for the practitioner. The clinical outcome of the restoration is influenced mainly by the material and its handling than by the fabrication process (i.e., CAD/CAM). Information on the restorative materials performances can be difficult to gather and compare. The aim of this article is to provide an overview of chairside CAD/CAM materials, their classification, and clinically relevant aspects that enable the reader to select the most appropriate material for predictable success.

Therapeutic Approach in the Treatment of Medication-Related Osteonecrosis of the Jaw: Case Series of 3 Patients and State of the Art on Surgical Strategies.

BACKGROUND: Bisphosphonates and receptor activator of nuclear factor kappa-B ligand inhibitors are currently the most widely used antiresorptive therapies in bone metabolism diseases treatment. Unfortunately they can evoke medication-related osteonecrosis of the jaws. The present case series study proposes to evaluate clinical features, evolution and the surgical therapeutic approaches in three patients affected by medication-related osteonecrosis of the jaw and to review the state of art regarding the management of this complication in light of the most recent literature. METHODS: Three cases of medication-related osteonecrosis of the jaws are discussed, two related to bisphosphonates therapy (ibandronic acid) and one due to denosumab. RESULTS: All three patients were aged female and had probably a dental trigger agent. The lesions located in posterior mandible were treated in one case with the surgical approach alone and, in the other case, with surgical approach associated with Erb-YAG laser. The lesion related to denosumab was treated with surgical approach and platelet rich fibrin application. A complete healing was always achieved. CONCLUSIONS: Dentists should be aware of the potential risk of developing medication-related osteonecrosis of the jaws for patients who take or had taken antiresorptive drugs. The side effects of denosumab and bisphosphonates are partly overlapping and currently there is still no consensus about the therapeutic surgical options. Prevention and early detection of the lesions should be the primary strategy.

Elongation of the styloid processes in kidney-transplanted patients: The role of ectopic calcification as possible cause of Eagle syndrome.

Objective: To investigate the relationship between the presence of ectopic calcification in the elongation of the styloid process (SP) and its possible clinical manifestation (Eagle syndrome) in a population of kidney-transplant patients previously treated with hemodialysis.Methods: Digital orthopantomography of 92 kidney-transplanted patients and 68 control subjects were analyzed to measure the length of SPs. Calcium, phosphate, alkaline phosphatase, and parathyroid hormone (PTH) blood levels were also available for comparison.Results: The mean length of SPs was significantly different between groups, as were phosphate and PTH values.Discussion: Renal transplant patients who have been treated with hemodialysis present elongated SPs, presumably due to alterations in phosphate balance and PTH levels. Thus, in cases of orofacial pain in patients with a history of altered bone metabolism, particularly when due to renal insufficiency, Eagle syndrome should be suspected as the main cause of symptoms.

Modulatory Effects of Plant Polyphenols on Bone Remodeling: A Prospective View From the Bench to Bedside.

During the past, a more comprehensive knowledge of mechanisms implicated in bone resorption processes has driven researchers to develop a compound library of many small molecules that specifically interfere with the genesis of osteoclast precursors cells. Natural compounds that suppress osteoclast commitment may have therapeutic value in treating pathologies associated with bone resorption like osteoporosis, rheumatoid arthritis, bone metastasis, and periodontal disease. The present review is focused on the current knowledge on the polyphenols derived from plants that could be efficacious in suppressing osteoclast differentiation and bone resorption.

Factors Influencing the Onset of Intra- and Post- Operative Complications Following Tooth Exodontia: Retrospective Survey on 1701 Patients.

Complications after tooth extraction may occur because of several factors correlated to the patient's medical history, surgical site or type of intervention. The aim of this retrospective cohort study was to evaluate type and frequency of complications after exodontic surgery, its correlation with antibiotic administration and between patient's related systemic factors. From June 2015 until February 2016 1701 exodontic interventions, for a total of 2322 extracted teeth, were carried out at the Unit of Oral Surgery in Trieste. Descriptive statistic, and backward multiple logistic regressions were performed to identify the variables associated with the presence of post-operative alveolitis or any other post-operative complication. The presence of coagulopathy and smoking habit were related to high risk of post-operative alveolitis (OR = 5.51, p = 0.035 and OR = 2.5, p = 0.029, respectively). Tooth fracture was found to be correlated with higher probability of post-operative alveolitis (p = 0.001) and concomitant chemotherapy put at a higher risk post-operative complications, including alveolitis (OR = 29.5, p = 0.018). According to the present results, antibiotic consumption did not seem to reduce the incidence of post-operative infective complications (alveolitis). A careful analysis of medical history, the adequate surgical technique, and the correct instructions in post-surgical behavior, prevent the insurgence of intra and post-operative complications.

Breast adenocarcinoma MCF-7 cell line induces spontaneous osteoclastogenesis via a RANK-ligand-dependent pathway.

The metastasis of breast cancer to the skeleton is a serious clinical problem resulting in hypercalcemia, bone fragility and insurmountable pain. The invasion of bony tissue by neoplastic cells usually very rapidly affects the balance between bone apposition and bone resorption. In order to elucidate a mechanism for cancer-induced osteoclastogenesis, cells from a human breast cancer line, MCF-7, were directly co-cultured with murine monocytes RAW 264.7 type CRL 2278. Compared with controls, co-culture of MCF-7 induced differentiation of multinucleated cells by membrane-bound and soluble receptor activator of NF-kB ligand (RANKL) as quantified by ELISA, Western blot analysis, transmission electron microscopy (TEM), and immunocytochemistry. The aim of this study was to determine an in vitro model system of MCF-7 human breast cancer cells grown together with monocytes to show that expression of RANKL promotes osteoclastogenesis, which may indicate a mechanism for the development of osteolytic lesions in breast cancer bone metastasis.

Dental Care for Patients with End-Stage Renal Disease and Undergoing Hemodialysis.

Chronic renal failure is a progressive disease characterized by a gradual destruction of nephrons and a consequent reduction of kidney function. End-stage renal disease (ESRD) necessitates renal replacement therapy as peritoneal dialysis, hemodialysis, or transplantation. Patients affected by ESRD or in hemodialysis are at risk for developing a number of comorbidities including hypertension, anemia, risk of bleeding, susceptibility to infection, medication side effects, and oral manifestations associated with the disease itself and with hemodialysis treatment. In this context, oral diseases represent a potential and preventable cause of poor health outcomes in people with ESRD due to their relation to infection, inflammation, and malnutrition. The aim of this article was to review ESRD and hemodialysis-associated manifestations and to describe the dental operative protocols for patients awaiting kidney transplantation in light of the most recent literature.

Effects of neridronic acid on osteoclasts derived by physiological dual-cell cultures.

Increased osteoclastic activity is observed in many osteopathic disorders - including postmenopausal osteoporosis, Paget's disease, primary bone tumours, lytic bone metastases, multiple myeloma and rheumatoid arthritis - that involve increased bone resorption and a loss of bone mass. Bisphosphonates are highly effective inhibitors of bone resorption that selectively affect the osteoclasts. The aim of this study was to obtain more information about the mechanism of action of bisphosphonates such as neridronic acid using a dual-cell culture model. As a model of osteoclastogenesis we used a murine monocyte/macrophage cell line RAW 264.7 type CRL 2278 co-cultured with murine osteoblasts. The monocyte-osteoblast system allows physiological experimentation of bone anti-resorption drugs, simulating bone turnover in pathologies such as osteoporosis. The direct actions of neridronic acid on cell proliferation and functionality in the co-culture model were examined using tartrate-resistant acid phosphatase (TRAP) assay, immunohistochemical localization of actin, and transmission and scanning electron microscopy (SEM). Results showed that the percentage of TRAP-positive cells, an early marker of osteoclastic differentiation, was significantly higher in control cultures than in co-cultures treated with variable concentrations of neridronic acid. Neridronic acid induced dramatic morphological changes, characterized by the loss of the ruffled border. The actin ring associated with the plasma membrane of the cells treated with neridronic acid was shown to break down. The tissue-specific targeting of neridronic acid to bone mineral suggests that it may inhibit bone resorption by direct effects on osteoclasts or other bone cells in the immediate microenvironment of the osteoclasts. From our study, we conclude that structural alterations induced by neridronic acid in our co-culture system lead to decreased osteoclast function. This may encourage the use of neridronic acid to reduce bone resorption in the therapy of demineralizing metabolic bone disorders.

In vitro exposure of human chondrocytes to pulsed electromagnetic fields.

The effect of pulsed electromagnetic fields (PEMFs) on the proliferation and survival of matrix-induced autologous chondrocyte implantation (MACI)-derived cells was studied to ascertain the healing potential of PEMFs. MACI-derived cells were taken from cartilage biopsies 6 months after surgery and cultured. No dedifferentiation towards the fibro- blastic phenotype occurred, indicating the success of the surgical implantation. The MACI-derived cultured chondrocytes were exposed to 12 h/day (short term) or 4 h/day (long term) PEMFs exposure (magnetic field intensity, 2 mT; frequency, 75 Hz) and proliferation rate determined by flow cytometric analysis. The PEMFs exposure elicited a significant increase of cell number in the SG2M cell cycle phase. Moreover, cells isolated from MACI scaffolds showed the presence of collagen type II, a typical marker of chondrocyte functionality. The results show that MACI membranes represent an optimal bioengineering device to support chondrocyte growth and proliferation in surgical implants. The surgical implant of MACI combined with physiotherapy is suggested as a promising approach for a faster and safer treatment of cartilage traumatic lesions.

Autophagy Inhibition Favors Survival of Rubrospinal Neurons After Spinal Cord Hemisection.

Spinal cord injuries (SCIs) are devastating conditions of the central nervous system (CNS) for which there are no restorative therapies. Neuronal death at the primary lesion site and in remote regions that are functionally connected to it is one of the major contributors to neurological deficits following SCI.Disruption of autophagic flux induces neuronal death in many CNS injuries, but its mechanism and relationship with remote cell death after SCI are unknown. We examined the function and effects of the modulation of autophagy on the fate of axotomized rubrospinal neurons in a rat model of spinal cord dorsal hemisection (SCH) at the cervical level. Following SCH, we observed an accumulation of LC3-positive autophagosomes (APs) in the axotomized neurons 1 and 5 days after injury. Furthermore, this accumulation was not attributed to greater initiation of autophagy but was caused by a decrease in AP clearance, as demonstrated by the build-up of p62, a widely used marker of the induction of autophagy. In axotomized rubrospinal neurons, the disruption of autophagic flux correlated strongly with remote neuronal death and worse functional recovery. Inhibition of AP biogenesis by 3-methyladenine (3-MA) significantly attenuated remote degeneration and improved spontaneous functional recovery, consistent with the detrimental effects of autophagy in remote damage after SCH. Collectively, our results demonstrate that autophagic flux is blocked in axotomized neurons on SCI and that the inhibition of AP formation improves their survival. Thus, autophagy is a promising target for the development of therapeutic interventions in the treatment of SCIs.

Morphological features of osteoclasts derived from a co-culture system.

The interaction between the receptor activator of NfKB (RANK) and its ligand receptor activator of NfKB ligand (RANKL) has recently been proven to be pivotal for osteoclast differentiation and activation. The influence of RANK-RANKL signaling on osteoclast formation was established by co-culturing murine osteoblasts (type CRL-12257) and murine mononuclear monocytes (RAW 264.7). The aim of the present study was to examine, by means of morphological techniques, the interaction between these two cell lines grown in the absolute absence of exogenous cytokines and other stimulating factors. Moreover, we wanted to show that our model could provide a system to analyze the bone resorption process. Mineralized matrix induced morphological changes of osteoclasts (OC) by the formation of organized ruffled-border and a large number of secondary lysosomal vesicles. On the contrary, OC grown on glass coverslips without dentin showed no organized ruffled border or secondary lysosomes. The study of the relationship between these two cell types could establish new approaches for a potential pharmacological control of these cell types and tissues in health and disease.

TRAIL, caspases and maturation of normal and leukemic myeloid precursors.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) is a membrane-bound cytokine molecule that belongs to the family of tumor necrosis factor (TNF). Members of this family share diverse biological effects, including induction of apoptosis and/or promotion of cell survival. Identification of TRAIL has generated considerable enthusiasm for its ability to induce apoptotic cell death in a variety of tumor cells, by engaging the death receptors TRAIL-R1/DR4 and TRAIL-R2/DR5, while sparing most normal cells. Beside its anticancer activity, several studies have suggested a role for endogenously expressed TRAIL in hemopoiesis. In this review, we summarize the knowledge about the different lineage-specific roles of TRAIL and its receptors in hemopoiesis regulation. Moreover, the complex interplay among the signaling pathways triggered by TRAIL/TRAIL-receptors in myeloid cells is discussed in some detail.

Osteoimmunology represents a link between skeletal and immune system.

There is a complex interplay between the cells of the immune system and bone. These inter- actions are not only mediated by the release of cytokines and chemokines but also by direct cell-cell contact. Studies of intracellular signaling mechanisms in osteoclasts have revealed that numerous immunomodulatory molecules are involved in the regulation of bone metabolism. Recently, it was proposed that immunoreceptors found in the immune cells are also an essen- tial signal for osteoclasts activation, along with receptor activator of NF-icB (RANK) ligand (RANKL). Collectively, these and similar observations regarding cross-regulation between the immune and skeletal systems constitute the field of osteoimmunology. Here we briefly high- light core areas of interest and selected recent advances in this field.

Immunolocalisation of bilitranslocase in mucosecretory and parietal cells of the rat gastric mucosa.

Bilitranslocase is a plasma membrane carrier localised at the vascular pole of the rat liver cell, where it mediates uptake of organic anions from the blood into the liver. This carrier is also present in the epithelium of the rat gastric mucosa, with similar molecular mass and functional properties. An immunohistochemical study reveals that both the mucus-secreting cells of the gastric pit and the H+-secreting parietal cells express bilitranslocase. These data point to a possible role of bilitranslocase and of its food-borne substrates (anthocyanins and nicotinic acid) in regulating the function and the permeability of the gastric mucosa.