Long-term stability (21-30 years) of root coverage outcomes using sub-epithelial connective tissue grafts at single or multiple gingival recessions: A longitudinal case series.

AIM: To evaluate outcomes and predictive factors for the long-term stability of root coverage using a sub-epithelial connective tissue graft. MATERIALS AND METHODS: One-hundred and two healthy subjects (221 gingival recessions, GRs) were treated from 1987 to 1996. Keratinized tissue width (KTW), GR depth (RD), GR width (RW) and GR area (RA) were evaluated at baseline (M0) and at 1 month (M1), 1 year (M2), 11 years (M3), 21 years (M4) and 27 years (M5) after surgery. Primary outcomes consisted of complete root coverage (cRC) and relative dimensional changes in recession depth (measured in mm [c%-RD]), recession width (measured in mm [c%-RW]) and recession area (measured in mm2 [c%-RA]). RESULTS: cRC was 88.7% at 1 year (M2), 59.8% at M3, 44.4% at M4 and 51.9% at M5. Average c%-RD was 95.2% at 1 year, 81.9% at M3, 71.5% at M4 and 81.7% at M5. KTW increased after surgery and over time and was positively correlated with favourable outcomes. Increased baseline RA was associated with less favourable clinical outcomes. CONCLUSIONS: The sub-epithelial connective tissue graft is effective in the treatment of GRs and facilitates long-term stability of clinical outcomes. Wider baseline RA was a strong predictor of unfavourable short- and long-term RC outcomes.

Clinical and histological reaction of periodontal tissues to subgingival resin composite restorations.

OBJECTIVES: To compare the clinical and histological response of supracrestal periodontal tissues to subgingival composite restorations versus natural root surfaces MATERIAL AND METHODS: In 29 subjects with a single tooth requiring subgingival restorations, a deep margin elevation (DME) procedure with composite resin was applied. Full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS), and focal probing depth (PD) were measured at baseline, before DME, and after 3 months. The distance between the coronal marked (CM) point to the apical margin of the composite reconstruction (AMR), at baseline, and to the tip of the periodontal probe inserted to reach the bottom of the sulcus (APP), 3 months later, was measured. An all-around secondary flap, harvested to ensure the subsequent single-crown prosthetic rehabilitation was histologically processed. The histological inflammation degree was evaluated in areas of gingival tissues adjacent to the composite (group B) and adjacent to the natural surface of each single tooth (group A). RESULTS: Significant FMPS, FMBS, and PD decreases were observed (p < 0.05). CM-AMR and CM-APP were significantly different (p < 0.05), suggesting an attachment gain after 3-months. The inflammation level of gingival tissue was similar in groups A and B (p > 0.05). CONCLUSIONS: For the first time, this topic was clinically and histologically studied in humans. Subgingival restorations resulted compatible with gingival health, with levels similar to that of untreated root surfaces. CLINICAL RELEVANCE: Deep margin elevation procedure produces favorable clinical and histological outcomes allowing a routine utilization in reconstructive dentistry.

Biological width establishment around dental implants is influenced by abutment height irrespective of vertical mucosal thickness: A cluster randomized controlled trial.

OBJECTIVE: Prosthetic abutment height and peri-implant mucosal thickness are considered factors that influence marginal bone remodeling during biological width establishment around dental implants. However, no clinical studies have evaluated their simultaneous effect on marginal bone loss (MBL). This study analyzes the influence of abutment height on MBL around implants surrounded by both thin and thick mucosa up to 12 months after prosthetic loading. MATERIAL AND METHODS: Seventy platform-switched implants with internal hex were placed equicrestally in two groups of patients with different vertical mucosal thickness: thin (≤2.0 mm) and thick mucosa (>2.0 mm). After three months of submerged healing, prosthetic abutments with a height of 1 mm (short) or 3 mm (long) were randomly assigned for single crown screwed restoration in both groups. MBL was evaluated on radiographs taken at implant placement (T0 ), restoration delivery (T1 ), and after 6 months (T2 ) and 12 months (T3 ) of loading. RESULTS: After 12 months of loading, 66 implants were functioning (two dropouts, two failures), resulting in a 97% survival rate. Compared with T0 , mean MBL at T3 ranged between 0.59 and 0.80 mm in short abutment groups and between 0.28 and 0.37 mm in long abutment groups. Differences resulted statistically significant, irrespective of vertical peri-implant mucosal thickness. The MBL pattern over time showed the greatest amount of bone resorption in the first 6 months after loading, particularly around implants with short abutments. CONCLUSIONS: Platform-switched implants restored with short abutments present greater marginal bone loss than identical implants with long abutments, without significant peri-implant mucosal thickness effects.

Mechanisms of Hydrogen Sulfide against the Progression of Severe Alzheimer's Disease in Transgenic Mice at Different Ages.

Backgroud: Alzheimer disease is an age-related severe neurodegenerative pathology. The level of the third endogenous gas, hydrogen sulfide (H2S), is decreased in the brain of Alzheimer's disease (AD) patients compared with the brain of the age-matched normal individuals; also, plasma H2S levels are negatively correlated with the severity of AD. Recently, we have demonstrated that systemic H2S injections are neuroprotective in an early phase of preclinical AD. OBJECTIVES: This study focuses on the possible neuroprotection of a chronic treatment with an H2S donor and sulfurous water (rich of H2S) in a severe transgenic 3×Tg-AD mice model. METHOD: 3×Tg-AD mice at 2 different ages (6 and 12 months) were daily treated intraperitoneally with an H2S donor and sulfurous water (rich of H2S) for 3 months consecutively. We investigated the cognitive ability, brain morphological alterations, amyloid/tau cascade, excitotoxic, inflammatory and apoptotic responses. RESULTS: Three months of treatments with H2S significantly protected against impairment in learning and memory in a severe 3×Tg-AD mice model, at both ages studied, and reduced the size of Amyloid ß plaques with preservation of the morphological picture. This neuroprotection appeared mainly in the cortex and hippocampus, associated with reduction in activity of c-jun N-terminal kinases, extracellular signal-regulated kinases and p38, which have an established role not only in the phosphorylation of tau protein but also in the inflammatory and excitotoxic response. CONCLUSION: Our findings indicate that appropriate treatments with various sources of H2S, might represent an innovative approach to counteract early and severe AD progression in humans.

Gingival tissue reaction to direct adhesive restoration: A preliminary study.

INTRODUCTION: It is debated whether composite resin marginal/submarginal direct restoration can be usefully performed without inflammatory consequences. This histological study is the first human analysis aimed to compare, in the same tooth, the gingival tissue close to composite resin restorations with gingival tissue close to hard tissue. METHODS: Eight healthy patients with almost a residual strategic tooth needing endodontic therapy, and post-and-core restoration, then indirect prosthetic restoration, were selected. Direct margin relocation with composite resin was necessary to perform endodontic treatment. The crown lengthening with a secondary flap harvested was necessary to perform prosthetic rehabilitation. Three months after marginal relocation, the secondary flap was harvested, embedded in PMMA, 4-µm sectioned, and stained to analyze the inflammation degree. RESULTS: All patients completed post-and-core reconstruction and the planned prosthetic therapy, maintaining the stringent hygienic protocol plan. The inflammation level comparison, slightly lower in gingiva close to the teeth (3.62 ± 0.38) than in gingiva close to the composite (3.75 ± 0.26), results in a p-value of 0.11 after Wilcoxon test. CONCLUSIONS: Results highlight a minimal, statistically not significant difference in the inflammation degree after margin relocation, conceivably due to patients, teeth and cases selection, together with adopted stringent methodological and supportive measures.

Are periodontal outcomes affected by personality patterns? A 18-month follow-up study.

OBJECTIVES: This research aims to study the relationship between personality traits and periodontal clinical outcomes by taking into account the level of anxiety and depression, periodontal health and oral hygiene behaviour of patients affected with gingivitis or moderate periodontitis requiring periodontal therapy. MATERIAL AND METHODS: The periodontal data of 40 systemically healthy patients affected by gingivitis or moderate periodontitis were collected at baseline and 18 months later. The psychological variables, dental awareness and adherence intent of the patients were assessed through questionnaires, and only those patients that exhibited a higher degree of compliance were included in the study. The personality traits (cluster A: paranoid, schizoid, schizotypal; cluster B: borderline, antisocial, narcissistic, and histrionic; cluster C: avoidant, dependent, and obsessive-compulsive) and the level of anxiety and depression of the patients were assessed. Patients were instructed with oral hygiene measures and were treated with periodontal therapy. RESULTS: Clusters A and B showed a consistent tendency for reduced levels of oral hygiene (increased full-mouth plaque score - FMPS). The results from cluster B were found to be significantly related to deep periodontal pockets at baseline. On the contrary, cluster C seemed to be linked to clinically better indices, particularly in terms of full-mouth-bleeding-score and pocket depth, both at baseline and 18 months later. The results collected from clusters B and C were directly correlated with anxiety, depression and FMPS. Moreover, anxiety was directly correlated with the patient's need for professional oral-care. CONCLUSIONS: Personality traits appear to play a significant role in determining the therapeutic outcomes of periodontal therapy in themselves. Thus, it is ideal for several important psychological, affective or behavioural factors to be associated with various personality traits so as to orient the outcome of periodontal therapy.

Effects of COX1-2/5-LOX blockade in Alzheimer transgenic 3xTg-AD mice.

OBJECTIVE AND DESIGN: Alzheimer's disease (AD) is associated with amyloid plaques (Aß) and hyperphosphorylated tau protein tangles in the brain. We investigated the possible neuroprotective role of flavocoxid, a dual inhibitor of cyclooxygenases-1/2 (COX-1/2) and 5-Lipoxygenase (5-LOX), in triple-transgenic (3xTg-AD) mice. SUBJECTS: Mice were 3 months at the beginning of the study. TREATMENT: Animals received once daily for 3-month saline solution or flavocoxid (20 mg/kg/ip). METHODS: Morris water maze was used to assess learning and memory. Histology was performed to evidence Aß plaques and neuronal loss, while inflammatory proteins were determined by western blot analysis. RESULTS: Saline-treated 3xTg-AD mice showed an impairment in spatial learning and memory (assessed at 6 months of age), and increased expression of inflammatory and apoptotic molecules. Treatment of 3xTg-AD mice with flavocoxid reduced: (1) learning and memory loss; (2) the increased eicosanoid production and the phosphorylation level of amyloid precursor protein (APP-pThr668), Aß 1-42, p-tau (pThr181), pERK, and the activation of the NLRP3 inflammasome; (3) Aß plaques; and (4) neuronal loss, compared to saline-treated animals. CONCLUSIONS: Pharmacological blockade of both COX-1/2 and 5-LOX was able to counteract the progression of AD by targeting pathophysiological mechanisms up- and downstream of Aß and tau.

The maintenance of inserted titanium implants: in-vitro evaluation of exposed surfaces cleaned with three different instruments.

OBJECTIVE: Changes to titanium implants smooth-surfaces after instrumentation were comparatively analyzed using low-vacuum scanning electron microscopy (LV-SEM) and white-light confocal (WLC) profilometry, to accurately evaluate curved surfaces. MATERIAL AND METHODS: Sixty titanium implants screwed to their abutments were randomly split into three groups for cleaning treatment with (S) stainless-steel Gracey-curettes, (T) titanium Langer-curettes, and (P) an ultrasonic-device with the probe covered with a plastic-tip. One sector of each implant was left unprocessed (U). The other sectors were cleaned for either 60 s, to simulate a single cleaning session, or 180 s to simulate a series of sessions. Surface morphology was analyzed by LV-SEM, without metal sputtering. Quantitative evaluations of the roughness of surfaces were performed using a WLC-profilometer. The Wilcoxon and the Mann-Whitney tests were used in statistical comparisons. RESULTS: U-surfaces showed that thin transverse ridges and grooves, i.e. a polarized surface roughness was substantially compromised after S-instrumentation. Small surface alterations, increasing with time, were also recorded after T-·and·P-instrumentation, although to a lesser degree. The gap of the fixture-abutment connection appeared almost completely clean after T-, clotted with titanium debris after S-, and clotted with plastic debris after P-treatment. The mean roughness (Ra) was unchanged after P-, significantly increased after S- and decreased after T-treatment, when compared with U. The Rz roughness-parameter, calculated along the fixture Y-axis, of S, T, and P resulted similar and significantly lower than that of U. Rz (X-axis) resulted unchanged after P-, slightly increased (+40%) after T-, and greatly increased (+260%) after S-treatment, this latter being statistically significant when compared with U. CONCLUSIONS: The careful use of titanium-curettes could produce only minimal smooth surface alteration particularly over prolonged treatments, and avoid debris production that could endanger implant preservation.

Piezosurgical treatment of crestal bone: quantitative comparison of post-extractive socket outcomes with those of traditional treatment.

OBJECTIVE: The study aimed to quantitatively compare, for the first time, the clinical outcomes of crestal bone volume resorption in sockets undergoing traditional extraction technique (TET) or piezosurgical extraction technique (PET), also considering the influence of buccal plate thickness. MATERIAL AND METHODS: In this prospective study, 19 sockets were randomly treated with TET, and 18 sockets were randomly treated with PET. Furthermore, patients were split into subgroup A, with buccal bone plate thickness (BPT) ≤1 mm, and subgroup B, with BPT>1 mm. Buccal (BCH) and palatal (PCH) cortex height, bucco-palatal ridge (BPR) width were monitored at tooth extraction and after the 4-month post-extractive period of natural healing. RESULTS: After 4 months, BCH, PCH and BPR width decreased more in the TET than in the PET group, but only the BPR decrease was statistically significant (P = 0.034) after ANOVA test. In both TET and PET groups, all B subgroup patients showed a lower decrease than A subgroup patients for both BCH, PCH and BPR, statistically significant for PCH (P = 0.019) and BPR (P < 0.001) of TET group, and BPR (P = 0.002) of PET group, after ANOVA. Both A and B subgroups of PET showed a statistically significant lower decrease than the corresponding subgroups of TET, comparing A (P = 0.005) and B (P = 0.037) subgroups for BPR, after ANOVA. CONCLUSIONS: With both thin and thick buccal plates, the piezosurgical extraction technique of teeth significantly decreases the horizontal resorption of the hard tissue ridge, but not the vertical resorption. Moreover, buccal plate thickness seems to be a key factor in post-extractive bone resorption: the thinner the buccal plate the greater the horizontal crestal bone loss.

NDP-α-MSH induces intense neurogenesis and cognitive recovery in Alzheimer transgenic mice through activation of melanocortin MC4 receptors.

Melanocortins exert neuroprotection in a variety of experimental neurodegenerative disorders, including Alzheimer's disease (AD). Further, in previous research we showed that these endogenous peptides stimulate neurogenesis in an acute neurodegenerative disorder such as ischemic stroke. In the present research, we investigated the potential neurogenic effect of melanocortins in AD using APPSwe transgenic mice (Tg2576). To this purpose, 24week-old animals were prepared for 5-bromo-2'-deoxyuridine (BrdU) labeling of proliferating cells on days 1-11 of the study. Treatment of Tg2576 mice with nanomolar doses of the melanocortin analog [Nle(4),D-Phe(7)]α-melanocyte-stimulating hormone (NDP-α-MSH), administered once daily from day 1 to 50, improved brain histology and cognitive functions relative to saline-treated Tg2576 animals. No signs of toxicity were observed. Immunohistochemical examination of the hippocampus at the end of the study (day 50) showed that NDP-α-MSH-treated Tg2576 mice had a greater number of BrdU immunoreactive cells colocalized with NeuN (an indicator of mature neurons) and Zif268 (an indicator of functionally integrated neurons) in the dentate gyrus, relative to saline-treated Tg2576 animals; no newly formed astrocytes were found. Animal pretreatment with the selective melanocortin MC4 receptor antagonist HS024 before each NDP-α-MSH administration prevented all the beneficial effects of the peptide. The present data indicate that MC4 receptor stimulation by a melanocortin prevents cognitive decline in experimental AD, this effect being associated not only with neuroprotection but also with an intense neurogenesis. MC4 receptor agonists could be innovative and safe candidates to counteract AD progression in humans.

Analysis of protein expression in periodontal pocket tissue: a preliminary study.

BACKGROUND: The periodontal disease is caused by a set of inflammatory disorders characterized by periodontal pocket formation that lead to tooth loss if untreated. The proteomic profile and related molecular conditions of pocket tissue in periodontally-affected patients are not reported in literature. To characterize the proteomic profile of periodontally-affected patients, their interproximal periodontal pocket tissue was compared with that of periodontally-healthy patients. Pocket-associated and healthy tissue samples, harvested during surgical therapy, were treated to extract the protein content. Tissues were always collected at sites where no periodontal-pathogenic bacteria were detectable. Proteins were separated using two-dimensional gel electrophoresis and identified by liquid chromatography/mass spectrometry. After identification, four proteins were selected for subsequent Western Blot quantitation both in pathological and healty tissues. RESULTS: A significant unbalance in protein expression between healthy and pathological sites was recorded. Thirty-two protein spots were overall identified, and four proteins (S100A9, HSPB1, LEG7 and 14-3-3) were selected for Western blot analysis of both periodontally-affected and healthy patients. The four selected proteins resulted over-expressed in periodontal pocket tissue when compared with the corresponding tissue of periodontally-healthy patients. The results of Western blot analysis are congruent with the defensive and the regenerative reaction of injured periodontal tissues. CONCLUSIONS: The proteomic analysis was performed for the first time directly on periodontal pocket tissue. The proteomic network highlighted in this study enhances the understanding of periodontal disease pathogenesis necessary for specific therapeutic strategies setting.

Maxillary sinus augmentation by crestal access: a retrospective study on cavity size and outcome correlation.

OBJECTIVE: Cone-beam computed tomography (CBCT) and radiographic outcomes of crestal sinus elevation, performed using mineralized human bone allograft, were analyzed to correlate results with maxillary sinus size. MATERIAL AND METHODS: A total of 60 sinus augmentations in 60 patients, with initial bone ≤5 mm, were performed. Digital radiographs were taken at surgical implant placement time up to post-prosthetic loading follow-up (12-72 months), when CBCT evaluation was carried out. Marginal bone loss (MBL) was radiographically analyzed at 6 months and follow-up time post-loading. Sinus size (BPD), implant distance from palatal (PID) and buccal wall (BID), and absence of bone coverage of implant (intra-sinus bone loss--IBL) were evaluated and statistically evaluated by ANOVA and linear regression analyses. RESULTS: MBL increased as a function of time. MBL at final follow-up was statistically associated with MBL at 6 months. A statistically significant correlation of IBL with wall distance and of IBL/mm with time was identified with greater values in wide sinuses (WS ≥ 13.27 mm) than in narrow sinuses (NS < 13.27 mm). CONCLUSIONS: This study is the first quantitative and statistically significant confirmation that crestal technique with residual ridge height <5 mm is more appropriate and predictable, in terms of intra-sinus bone coverage, in narrow than in WS.

Stage Characterization and Marginal Bone Loss Evaluation Up to 96 Months of Crestal Sinus Augmentation With Sequential Drills: A Retrospective Study.

INTRODUCTION: The 2-stage crestal approach to augment the maxillary sinus is a little-used technique. The aim of this retrospective study was to assess events characterizing stages of this technique after implant placement in the posterior maxilla with residual bone height less than 4 mm and evaluate the marginal bone loss (MBL) changes over time. MATERIAL AND METHODS: Thirty-three patients underwent unilateral sinus augmentations using the trancrestal technique with mineralized allograft. Six-months (6 m) after first surgery, if skeletal subsidence prevented insertion of a 10-mm-length implant, additional grafting was performed during implant (n = 33) insertion. Radiographs were taken before grafting (baseline), immediately after and at 6 months; immediately after and 6 months after implant placement; and at follow-up (24-96 m). RESULTS: One implant was lost (ISR = 96.97%). Of the remaining 32 patients, 14 (A group) underwent standard implant placement, whereas 18 (B group) underwent additional grafting immediately before implant placement. Given that B-group patients initially obtained lower crestal bone height after first surgery, additional grafting procedures provided greater crestal height in the B group. A significant relationship between ending (eMBL) and 6mMBL was found in both groups, with greater values in the B group. However, in both groups, eMBL was always greater if 6mMBL was greater than 0.44 mm. DISCUSSION: Results suggest a high and low skeletal-reactivity patient categorization. In both patient categories, MBL greatly depends upon 6-month values. Investigations are necessary to relate sinus size with results obtained by this 2-stage crestal approach. CONCLUSIONS: The 2-stage crestal sinus lift procedure not only provides predictable results, but also allows low skeletal-reactivity patient recovery.

Is socket healing conditioned by buccal plate thickness? A clinical and histologic study 4 months after mineralized human bone allografting.

OBJECTIVE: The aim of this study was to clinically and histologically analyze the healing of grafted sockets by mineralized human bone allograft (MHBA) and nongrafted sockets, correlating the results with buccal plate thickness. MATERIAL AND METHODS: Thirty-one sockets were randomly split into control (CG) and treatment (MHBA grafted) (TG) groups and, subsequently, into four subgroups according to buccal plate thickness: a ≤ 1 mm and b > 1 mm. Ridge thickness, depth, and height were monitored. Four months after, at implant placement, a bone core biopsy for histologic and morphometric analyses was taken. RESULTS: The differences of buccal height (TG-a -0.27 and CG-a -1.17 mm) and width (TG-a 0.55 and CG-a 2.67 mm, TG-b 0.12 and CG-b 1.17 mm) were statistically significant. The increase in bone amount CG-b (28.17%) compared with CG-a (16.98%) was statistically significant. Soft tissue amount of TG-b (54.21%) and TG-a (56.91%) was lower than that of CG-b (71.83%) and CG-a (83.01%), both being statistically significant (P = 0.002). CONCLUSIONS: The results proved that thin buccal plates had a worse outcome on socket healing and that network formation by MBHA not only predisposes a successful implant insertion but also acts as size keeper.

Microradiography and microcomputed tomography comparative analysis in human bone cores harvested after maxillary sinus augmentation: a pilot study.

OBJECTIVES: The aim of this study was to compare microradiography (MR) and microcomputed tomography (µCT) analysis of bone samples following maxillary sinus augmentation at different time periods and determine the relationships between measured area and volume fractions. MATERIALS AND METHODS: Lateral window sinus grafts were performed on 10 patients using a mineralized human bone allograft (MHBA). At implant placement, 5-13 months after surgery, 10 bone core biopsies were harvested. Prior to histologic sectioning, bone samples were evaluated with µCT. The morphometric parameters computed by MR and µCT were compared using Pearson's correlation and Bland and Altman analysis and included hard tissue fraction (HV/TV:%), soft tissue fraction (SV/TV:%), vital bone fraction (BV/TV:%) and residual graft fraction (GV/TV:%). RESULTS: Strong positive correlation between MR and µCT was found for HV/TV and SV/TV and BV/TV [r = 0.84, 0.84 and 0.69, respectively] but weak for GV/TV [r = 0.10]. CONCLUSION: µCT technology shows promising potential as an indicator of bone morphology changes; however, caution should be used in interpreting morphometric parameters, as the different methods reveal important biases.

Two-stage crestal sinus elevation by sequential drills in less than 4 mm of residual ridge height: a clinical and histologic case report.

PURPOSE: The aim of this work, the first human histologic case report of this technique, was a clinical and histologic evaluation of implant placed in a severely atrophic maxilla using a 2-stage crestal sinus elevation. CASE PRESENTATION: A 52-year-old woman required rehabilitation of an atrophic maxilla with a fixed implant-supported prosthesis. At the first surgery, a crestal sinus lift was performed using beta-tricalcium phosphate (ß-TCP), as radiographic tracer, and mineralized human bone allograft (MHBA) as grafting material. After 6 months, a bone core biopsy was taken, and 2 implants were placed in the augmented sites. Four months later, implants were exposed, and 2 splinted gold-porcelain crowns were delivered. Histology highlighted basal bone disappearance, replaced by a wide composite network (∼50% vol/vol) of MHBA granules connected by newly formed bone, and osteoblastic activities. CONCLUSION: This case report demonstrates the possibility of executing a staged transcrestal sinus lift in atrophic situations. MHBA evidenced usefulness in maintaining bone volume. Histologic analyses confirmed the sound outcome of the graft augmentation. Additional studies would be beneficial to confirm or refute the reliability of this technique.

A trabecular metal implant 4 months after placement: clinical-histologic case report.

INTRODUCTION: The aim of this case report was to histologically evaluate the behavior of a trabecular metal (TM) implant composed of titanium and spatial 3-dimensional tantalum (Ta) trabeculae. This study is the first human histologic case report of this implant. CASE PRESENTATION: A TM implant was placed in a 54-year-old woman exhibiting moderate chronic periodontitis. After periodontal treatment, the implant was inserted under favorable clinical conditions. Patient was not seen for 4 months because of unrelated breast reduction surgery. At the surgical reopening, periimplant inflammation affecting the coronal third of the implant was observed 4 months after implant placement. With patient's consent, the implant was removed for histologic analysis. Histology highlighted a greater amount of bone in close contact with Ta trabeculae than titanium surfaces. CONCLUSION: The finding of bone formation around the Ta trabeculae suggests that trabecular metal material promotes bone ingrowth for secondary implant stability. Additional evidence is needed to confirm this observation.

Hydrogen sulfide slows down progression of experimental Alzheimer's disease by targeting multiple pathophysiological mechanisms.

It has been previously reported that brain hydrogen sulfide (H2S) synthesis is severely decreased in Alzheimer's disease (AD) patients, and plasma H2S levels are negatively correlated with the severity of AD. Here we extensively investigated whether treatment with a H2S donor and spa-waters rich in H2S induces neuroprotection and slows down progression of AD. Studies with sodium hydrosulfide (a H2S donor) and Tabiano's spa-water were carried out in three experimental models of AD. Short-term and long-term treatments with sodium hydrosulfide and/or Tabiano's spa-water significantly protected against impairment in learning and memory in rat models of AD induced by brain injection of ß-amyloid1-40 (Aß) or streptozotocin, and in an AD mouse model harboring human transgenes APPSwe, PS1M146V and tauP301L (3xTg-AD mice). The improvement in behavioral performance was associated with hippocampus was size of Aß plaques and preservation of the morphological picture, as found in AD rats. Further, lowered concentration/phosphorylation levels of proteins thought to be the central events in AD pathophysiology, namely amyloid precursor protein, presenilin-1, Aß1-42 and tau phosphorylated at Thr181, Ser396 and Ser202, were detected in 3xTg-AD mice treated with spa-water. The excitotoxicity-triggered oxidative and nitrosative stress was counteracted in 3xTg-AD mice, as indicated by the decreased levels of malondialdehyde and nitrites in the cerebral cortex. Hippocampus reduced activity of c-jun N-terminal kinases, extracellular signal-regulated kinases and p38, which have an established role not only in phosphorylation of tau protein but also in inflammation and apoptosis, was also found. Consistently, decrease in tumor necrosis factor-α level, up-regulation of Bcl-2, and down-regulation of BAX and the downstream executioner caspase-3, also occurred in the hippocampus of 3xTg-AD mice after treatment with Tabiano's spa-water, thus suggesting that it is also able to modulate inflammation and apoptosis. Our findings indicate that appropriate treatments with H2S donors and Tabiano's spa-waters, and may be other spa-waters rich in H2S content, might represent an innovative approach to slow down AD progression in humans by targeting multiple pathophysiological mechanisms.

Modulation of the JAK/ERK/STAT signaling in melanocortin-induced inhibition of local and systemic responses to myocardial ischemia/reperfusion.

The janus kinases (JAK), extracellular signal-regulated kinases (ERK) and signal transducers and activators of transcription (STAT) pathways have been shown to play a cardioprotective role. We previously gave evidence that melanocortins afford cardioprotection in conditions of myocardial ischemia/reperfusion. Here we aimed to investigate the influence of melanocortins on the JAK/ERK/STAT signaling in cardiac and systemic responses to prolonged myocardial ischemia/reperfusion. Ischemia was produced in rats by ligature of the left anterior descending coronary artery for 30 min. At the end of the 2-h reperfusion, western blot analysis of the cardioprotective transcription factors pJAK2, pERK1/2, pTyr-STAT3 and pSer-STAT3, the inflammatory mediator tumor necrosis factor-α (TNF-α), the pro-apoptotic factors BAX and c-jun N-terminal kinases (pJNK), the anti-apoptotic protein Bcl-XL, as well as of the cardioprotective enzyme heme oxygenase-1 (HO-1), was performed in the left ventricle and spleen. Intravenous treatment, during coronary artery occlusion, with the melanocortin analogs [Nle(4), D-Phe(7)]α-melanocyte-stimulating hormone (NDP-α-MSH) and adrenocorticotropic hormone 1-24 [ACTH-(1-24)], induced a left ventricle up-regulation of pJAK2, pERK1/2 and pTyr-STAT3 (JAK-dependent), and a reduction in pJNK and TNF-α levels; these effects of NDP-α-MSH and ACTH-(1-24) were associated with over-expression of the pro-survival proteins HO-1 and Bcl-XL, and marked decrease of the myocardial infarct size. Melanocortin treatment did not affect left ventricle pSer-STAT3 (ERK1/2-dependent) and BAX levels. In the spleen, NDP-α-MSH and ACTH-(1-24) induced similar effects on the expression of the above transcription factors/proteins, except for pERK1/2 (down-regulated) and HO-1 (unaffected). Blockade of JAK and ERK pathways with AG490 and U0126, respectively, abrogated the myocardial infarct size reduction by NDP-α-MSH. These results indicate that melanocortins inhibit local and systemic inflammatory and apoptotic cascades triggered by prolonged myocardial ischemia/reperfusion, with consequent reduction in myocardium infarct size, seemingly via activation of the JAK/STAT signaling and with modulation of an ERK (STAT unrelated) signaling pathway.