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.

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.

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.

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.

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.

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.

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.

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.

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.

Effect of tanshinone II on cell growth of breast cancer cell line type MCF-7 and MD-MB-231.

Breast cancer is the most common form of cancer in women and the leading cause of cancer death in American women, with over 207,090 new cases of invasive breast cancer in women and about 39,840 deaths from breast cancer in 2010. Current therapies for breast cancer usually have variable effectiveness with high toxicity to normal tissues, and breast tumours often develop metastasis and drug resistance. Therefore, searching for effective regimens with minimal side effects remains the top priority in breast cancer research. The objectives of this study were to evaluate the effects of tanshinone II from a Chinese herb, Salvia miltiorrhiza, on the growth of breast cancer cells type MCF-7 and MDA-MB-231.

Targeting RANKL in the management of bone loss in patient with breast cancer.

The receptor activator of nuclear factor-kappaB ligand (RANKL), its signaling receptor RANK, and its natural decoy receptor OPG are members of the tumour necrosis factor (TNF) and TNF receptor superfamily and are best known for their essential role in controlling osteoclastogenesis. RANKL in bone has also been shown to serve as a chemoattractant for cancer cells, thu explaining the tropism of certain cancers such as breast and prostate cancer to preferentially metastasize to bone. Here, we will discuss the important role of RANKL and its possible role in the management of bone loss in patients with breast cancer.

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.

Morphological and bioenergetic demands underlying the mitophagy in post-mitotic neurons: the pink-parkin pathway.

Evidence suggests a striking causal relationship between changes in quality control of neuronal mitochondria and numerous devastating human neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Contrary to replicating mammalian cells with a metabolism essentially glycolytic, post-mitotic neurons are distinctive owing to (i) their exclusive energetic dependence from mitochondrial metabolism and (ii) their polarized shape, which entails compartmentalized and distinct energetic needs. Here, we review the recent findings on mitochondrial dynamics and mitophagy in differentiated neurons focusing on how the exceptional characteristics of neuronal populations in their morphology and bioenergetics needs make them quite different to other cells in controlling the intracellular turnover of these organelles.

Receptor Activator for Nuclear Factor kappa B Ligand (RANKL) as an osteoimmune key regulator in bone physiology and pathology.

The strength and integrity of the human skeleton depends on a delicate equilibrium between bone resorption and bone formation. Bone resorption is an elementary cellular activity in the modelling of the skeleton during growth and development. Later in life a most important physiological process in the skeleton is bone remodelling, which is locally initiated by resorption. During remodelling bone resorption is coupled to new bone formation that ensures renewal of bone with only minor local and temporary bone loss. Cells responsible for bone resorption and subsequent bone formation are the osteoclasts and osteoblasts, respectively. The osteoclast is derived from the pluripotent hematopoietic stem cell, which gives rise to a myeloid stem cell that can further differentiate into megakaryocytes, granulocytes, monocytes/macrophages and osteoclasts. The respective bone resorbing and forming actions of osteoclasts and osteoblasts are finely coupled, so that bone mass remains remarkably stable in a healthy adult. Imbalance between osteoclast and osteoblast activities can arise from a wide variety of hormonal changes or perturbations of inflammatory and growth factors resulting in postmenopausal osteoporosis, Paget's disease, lytic bone metastases, or rheumatoid arthritis, leading to increased bone resorption and crippling bone damage. In view of the critical role of osteoclasts in diverse pathology, there has been immense effort aimed at understanding the biology of this unique cell. The present review is focused on the current knowledge of the mechanisms that regulate the functional links between bone turnover and the immune system helping us to understand the main factors that lead to bone loss observed in osteoporosis, cancer and in rheumatoid arthritis. The aim of this review paper is to consider the key molecular interactions involved in the formation of osteoclast cells in normal and pathological conditions.

Expression of bilitranslocase in the vascular endothelium and its function as a flavonoid transporter.

AIMS: Ingestion of flavonoid-rich beverages acutely affects endothelial function, causing vasodilation. This effect might be dependent on flavonoid transport into the endothelium. We investigated flavonoid uptake into vascular endothelial cells and whether this was mediated by bilitranslocase (TC 2.A.65.1.1), a bilirubin-specific membrane carrier that also transports various dietary flavonoids. METHODS AND RESULTS: Human and rat aortic primary endothelial cells as well as Ea.hy 926 cells were found to express bilitranslocase, as assessed by immunocytochemistry and immunoblotting analysis using anti-sequence bilitranslocase antibodies targeting two distinct extracellular epitopes of the carrier. Bilitranslocase function was tested by measuring the rate of bromosulfophthalein (a standard bilitranslocase transport substrate) uptake into endothelial cells and was inhibited not only by bilitranslocase antibodies but also by quercetin (a flavonol). Similarly, uptake of both quercetin and malvidin 3-glucoside (an anthocyanin) were also found to be antibody-inhibited. Quercetin uptake into cells was inhibited by bilirubin, suggesting flavonoid uptake via a membrane pathway shared with bilirubin. CONCLUSION: The uptake of some flavonoids into the vascular endothelium occurs via the bilirubin-specific membrane transporter bilitranslocase. This offers new insights into the vascular effects of both flavonoids and bilirubin.

Soluble TRAIL could enhance bone destruction acting on Rank-ligand in estrogen-independent human breast cancer cell line MDA-MB-231.

The development and spread of tumors is associated with the ability of malignant cells to avoid detection and subsequent elimination by the immune system, to grow in non-native sites and to avoid programmed or induced cell death. In addition to the well-described role of osteoprotegerin in the regulation of bone turnover, there is an emerging evidence that osteoprotegerin may have an additional function due to its ability to bind and inhibit the members of the tumor necrosis factor (TNF)-superfamily, such as TNF-alpha and TNF-related apoptosis inducing ligand (TRAIL). We have shown that the breast cancer cell line MDA-MB-231 produces a sufficient amount of osteoprotegerin to bind TRAIL, resulting in an upregulation of receptor activator factor kappa B ligand (RANKL) expression. In conclusion, the presence of osteoprotegerin, as secreted by this cell line, acting as a paracrine factor, could affect breast cancer RANKL production inducing an enhancement of osteolysis and the perpetuation of a vicious cycle. A better understanding of the complex tumor cell-host cell interactions in the bone microenvironment, and of the autocrine and paracrine effects of the secreted (from tumor cells) and released (from bone matrix) factors may facilitate development of effective strategies to inhibit disease progression.