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1.
Proc Natl Acad Sci U S A ; 113(5): E568-76, 2016 Feb 02.
Article in English | MEDLINE | ID: mdl-26787865

ABSTRACT

There is a paucity of new therapeutic targets to control allergic reactions and forestall the rising trend of allergic diseases. Although a variety of immune cells contribute to allergy, cytokine-secreting αß(+)CD4(+) T-helper 2 (TH2) cells orchestrate the type-2-driven immune response in a large proportion of atopic asthmatics. To identify previously unidentified putative targets in pathogenic TH2 cells, we performed in silico analyses of recently published transcriptional data from a wide variety of pathogenic TH cells [Okoye IS, et al. (2014) Proc Natl Acad Sci USA 111(30):E3081-E3090] and identified that transcription intermediary factor 1 regulator-alpha (Tif1α)/tripartite motif-containing 24 (Trim24) was predicted to be active in house dust mite (HDM)- and helminth-elicited Il4(gfp+)αß(+)CD4(+) TH2 cells but not in TH1, TH17, or Treg cells. Testing this prediction, we restricted Trim24 deficiency to T cells by using a mixed bone marrow chimera system and found that T-cell-intrinsic Trim24 is essential for HDM-mediated airway allergy and antihelminth immunity. Mechanistically, HDM-elicited Trim24(-/-) T cells have reduced expression of many TH2 cytokines and chemokines and were predicted to have compromised IL-1-regulated signaling. Following this prediction, we found that Trim24(-/-) T cells have reduced IL-1 receptor (IL-1R) expression, are refractory to IL-1ß-mediated activation in vitro and in vivo, and fail to respond to IL-1ß-exacerbated airway allergy. Collectively, these data identify a previously unappreciated Trim24-dependent requirement for IL-1R expression on TH2 cells and an important nonredundant role for T-cell-intrinsic Trim24 in TH2-mediated allergy and antihelminth immunity.


Subject(s)
Hypersensitivity/immunology , Nuclear Proteins/physiology , Receptors, Interleukin-1/metabolism , Th2 Cells/immunology , Transcription Factors/physiology , Animals , Helminths/immunology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Nuclear Proteins/genetics , Th2 Cells/metabolism , Transcription Factors/genetics
2.
PLoS Pathog ; 12(4): e1005528, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27055274

ABSTRACT

Bacterial genotoxins, produced by several Gram-negative bacteria, induce DNA damage in the target cells. While the responses induced in the host cells have been extensively studied in vitro, the role of these effectors during the course of infection remains poorly characterized. To address this issue, we assessed the effects of the Salmonella enterica genotoxin, known as typhoid toxin, in in vivo models of murine infection. Immunocompetent mice were infected with isogenic S. enterica, serovar Typhimurium (S. Typhimurium) strains, encoding either a functional or an inactive typhoid toxin. The presence of the genotoxic subunit was detected 10 days post-infection in the liver of infected mice. Unexpectedly, its expression promoted the survival of the host, and was associated with a significant reduction of severe enteritis in the early phases of infection. Immunohistochemical and transcriptomic analysis confirmed the toxin-mediated suppression of the intestinal inflammatory response. The presence of a functional typhoid toxin further induced an increased frequency of asymptomatic carriers. Our data indicate that the typhoid toxin DNA damaging activity increases host survival and favours long-term colonization, highlighting a complex cross-talk between infection, DNA damage response and host immune response. These findings may contribute to understand why such effectors have been evolutionary conserved and horizontally transferred among Gram-negative bacteria.


Subject(s)
Asymptomatic Infections , Communicable Diseases/microbiology , Mutagens/toxicity , Salmonella typhimurium/pathogenicity , Typhoid Fever/microbiology , Animals , Intestines/microbiology , Macrophages/microbiology , Mice , Virulence
3.
Cell Microbiol ; 15(12): 2034-50, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23869968

ABSTRACT

Cytolethal-distending toxins (CDTs) belong to a family of DNA damage inducing exotoxins that are produced by several Gram-negative bacteria. Salmonella enterica serovar Typhi expresses its CDT (named as Typhoid toxin) only in the Salmonella-containing vacuole (SCV) of infected cells, which requires its export for cell intoxication. The mechanisms of secretion, release in the extracellular space and uptake by bystander cells are poorly understood. We have addressed these issues using a recombinant S. Typhimurium strain, MC71-CDT, where the genes encoding for the PltA, PltB and CdtB subunits of the Typhoid toxin are expressed under control of the endogenous promoters. MC71-CDT grown under conditions that mimic the SCV secreted the holotoxin in outer membrane vesicles (OMVs). Epithelial cells infected with MC71-CDT also secreted OMVs-like vesicles. The release of these extracellular vesicles required an intact SCV and relied on anterograde transport towards the cellular cortex on microtubule and actin tracks. Paracrine internalization of Typhoid toxin-loaded OMVs by bystander cells was dependent on dynamin-1, indicating active endocytosis. The subsequent induction of DNA damage required retrograde transport of the toxin through the Golgi complex. These data provide new insights on the mode of secretion of exotoxins by cells infected with intracellular bacteria.


Subject(s)
Bacterial Toxins/metabolism , Salmonella typhi/metabolism , Salmonella typhimurium/metabolism , Secretory Vesicles/metabolism , Amino Acid Sequence , Animals , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Bacterial Toxins/genetics , Brefeldin A/pharmacology , Caco-2 Cells , Cell Line , DNA Damage , Dynamin I/antagonists & inhibitors , Dynamin I/metabolism , Dynamins/antagonists & inhibitors , Endocytosis , Epithelial Cells/metabolism , Epithelial Cells/microbiology , HeLa Cells , Humans , Hydrazones/pharmacology , Mice , Promoter Regions, Genetic , Salmonella typhi/genetics , Salmonella typhi/pathogenicity , Salmonella typhimurium/genetics , Salmonella typhimurium/pathogenicity
4.
Cell Microbiol ; 15(1): 98-113, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22998585

ABSTRACT

Epidemiological evidence links chronic bacterial infections to the increased incidence of certain types of cancer but the molecular mechanisms by which bacteria contribute to tumour initiation and progression are still poorly characterized. Here we show that chronic exposure to the genotoxin cytolethal distending toxin (CDT) of Gram-negative bacteria promotes genomic instability and acquisition of phenotypic properties of malignancy in fibroblasts and colon epithelial cells. Cells grown for more than 30 weeks in the presence of sublethal doses of CDT showed increased mutation frequency, and accumulation of chromatin and chromosomal aberrations in the absence of significant alterations of cell cycle distribution, decreased viability or senescence. Cell survival was dependent on sustained activity of the p38 MAP kinase. The ongoing genomic instability was associated with impaired activation of the DNA damage response and failure to efficiently activate cell cycle checkpoints upon exposure to genotoxic stress. Independently selected sublines showed enhanced anchorage-independent growth as assessed by the formation of colonies in semisolid agarose. These findings support the notion that chronic infection by CDT-producing bacteria may promote malignant transformation, and point to the impairment of cellular control mechanisms associated with the detection and repair of DNA damage as critical events in the process.


Subject(s)
Bacterial Toxins/metabolism , DNA Damage/drug effects , Genomic Instability/drug effects , Gram-Negative Bacteria/pathogenicity , Mutagens/metabolism , Animals , Cell Line , Cell Survival/drug effects , Epithelial Cells/drug effects , Fibroblasts/drug effects , Humans , Rats
5.
J Cell Sci ; 124(Pt 16): 2735-42, 2011 Aug 15.
Article in English | MEDLINE | ID: mdl-21807938

ABSTRACT

The DNA damage response triggered by bacterial cytolethal distending toxins (CDTs) is associated with activation of the actin-regulating protein RhoA and phosphorylation of the downstream-regulated mitogen-activated protein kinase (MAPK) p38, which promotes the survival of intoxicated (i.e. cells exposed to a bacterial toxin) cells. To identify the effectors of this CDT-induced survival response, we screened a library of 4492 Saccharomyces cerevisiae mutants that carry deletions in nonessential genes for reduced growth following inducible expression of CdtB. We identified 78 genes whose deletion confers hypersensitivity to toxin. Bioinformatics analysis revealed that DNA repair and endocytosis were the two most overrepresented signaling pathways. Among the human orthologs present in our data set, FEN1 and TSG101 regulate DNA repair and endocytosis, respectively, and also share common interacting partners with RhoA. We further demonstrate that FEN1, but not TSG101, regulates cell survival, MAPK p38 phosphorylation, RhoA activation and actin cytoskeleton reorganization in response to DNA damage. Our data reveal a previously unrecognized crosstalk between DNA damage and cytoskeleton dynamics in the regulation of cell survival, and might provide new insights on the role of chronic bacteria infection in carcinogenesis.


Subject(s)
Bacterial Toxins/metabolism , Cell Survival , Cytoskeleton/metabolism , Flap Endonucleases/metabolism , rhoA GTP-Binding Protein/metabolism , Actins/metabolism , Bacterial Toxins/genetics , Cell Survival/genetics , Computational Biology , Cytoskeleton/ultrastructure , DNA Damage , DNA Repair/genetics , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Endocytosis/genetics , Endosomal Sorting Complexes Required for Transport/genetics , Endosomal Sorting Complexes Required for Transport/metabolism , Flap Endonucleases/genetics , HeLa Cells , Humans , Saccharomyces cerevisiae/genetics , Sequence Deletion/genetics , Signal Transduction/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Transgenes/genetics , p38 Mitogen-Activated Protein Kinases/metabolism
6.
Cell Rep ; 42(12): 113515, 2023 12 26.
Article in English | MEDLINE | ID: mdl-38096048

ABSTRACT

Argonaute (AGO) proteins execute microRNA (miRNA)-mediated gene silencing. However, it is unclear whether all 4 mammalian AGO proteins (AGO1, AGO2, AGO3, and AGO4) are required for miRNA activity. We generate Ago1, Ago3, and Ago4-deficient mice (Ago134Δ) and find AGO1/3/4 to be redundant for miRNA biogenesis, homeostasis, or function, a role that is carried out by AGO2. Instead, AGO1/3/4 regulate the expansion of type 2 immunity via precursor mRNA splicing in CD4+ T helper (Th) lymphocytes. Gain- and loss-of-function experiments demonstrate that nuclear AGO3 interacts directly with SF3B3, a component of the U2 spliceosome complex, to aid global mRNA splicing, and in particular the isoforms of the gene Nisch, resulting in a dysregulated Nisch isoform ratio. This work uncouples AGO1, AGO3, and AGO4 from miRNA-mediated RNA interference, identifies an AGO3:SF3B3 complex in the nucleus, and reveals a mechanism by which AGO proteins regulate inflammatory diseases.


Subject(s)
MicroRNAs , RNA Precursors , Animals , Mice , Argonaute Proteins/genetics , Argonaute Proteins/metabolism , Imidazoline Receptors/genetics , Imidazoline Receptors/metabolism , Mammals/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , RNA Interference , RNA Precursors/genetics , RNA Precursors/metabolism , RNA Splicing/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism
7.
Sci Transl Med ; 14(641): eabl8146, 2022 04 20.
Article in English | MEDLINE | ID: mdl-35442706

ABSTRACT

Asthma and inflammatory airway diseases restrict airflow in the lung, compromising gas exchange and lung function. Inhaled corticosteroids (ICSs) can reduce inflammation, control symptoms, and improve lung function; however, a growing number of patients with severe asthma do not benefit from ICS. Using bronchial airway epithelial brushings from patients with severe asthma or primary human cells, we delineated a corticosteroid-driven fibroblast growth factor (FGF)-dependent inflammatory axis, with FGF-responsive fibroblasts promoting downstream granulocyte colony-stimulating factor (G-CSF) production, hyaluronan secretion, and neutrophilic inflammation. Allergen challenge studies in mice demonstrate that the ICS, fluticasone propionate, inhibited type 2-driven eosinophilia but induced a concomitant increase in FGFs, G-CSF, hyaluronan, and neutrophil infiltration. We developed a model of steroid-induced neutrophilic inflammation mediated, in part, by induction of an FGF-dependent epithelial-mesenchymal axis, which may explain why some individuals do not benefit from ICS. In further proof-of-concept experiments, we found that combination therapy with pan-FGF receptor inhibitors and corticosteroids prevented both eosinophilic and steroid-induced neutrophilic inflammation. Together, these results establish FGFs as therapeutic targets for severe asthma patients who do not benefit from ICS.


Subject(s)
Asthma , Fibroblast Growth Factors , Adrenal Cortex Hormones/pharmacology , Adrenal Cortex Hormones/therapeutic use , Animals , Fluticasone/pharmacology , Fluticasone/therapeutic use , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Hyaluronic Acid , Inflammation/drug therapy , Mice
8.
Sci Transl Med ; 14(627): eabf8188, 2022 01 12.
Article in English | MEDLINE | ID: mdl-35020406

ABSTRACT

Exacerbations of symptoms represent an unmet need for people with asthma. Bacterial dysbiosis and opportunistic bacterial infections have been observed in, and may contribute to, more severe asthma. However, the molecular mechanisms driving these exacerbations remain unclear. We show here that bacterial lipopolysaccharide (LPS) induces oncostatin M (OSM) and that airway biopsies from patients with severe asthma present with an OSM-driven transcriptional profile. This profile correlates with activation of inflammatory and mucus-producing pathways. Using primary human lung tissue or human epithelial and mesenchymal cells, we demonstrate that OSM is necessary and sufficient to drive pathophysiological features observed in severe asthma after exposure to LPS or Klebsiella pneumoniae. These findings were further supported through blockade of OSM with an OSM-specific antibody. Single-cell RNA sequencing from human lung biopsies identified macrophages as a source of OSM. Additional studies using Osm-deficient murine macrophages demonstrated that macrophage-derived OSM translates LPS signals into asthma-associated pathologies. Together, these data provide rationale for inhibiting OSM to prevent bacterial-associated progression and exacerbation of severe asthma.


Subject(s)
Asthma , Oncostatin M/metabolism , Animals , Asthma/pathology , Humans , Lung/pathology , Macrophages/metabolism , Mice , Mucus , Oncostatin M/genetics
9.
Mucosal Immunol ; 14(4): 912-922, 2021 07.
Article in English | MEDLINE | ID: mdl-33846533

ABSTRACT

Acute exacerbations (AE) of asthma, remain one of the biggest concerns for patients living with asthma. As such, identifying the causes, the molecular mechanisms involved and new therapeutic interventions to prevent AE is a high priority. Immunity to intestinal helminths involves the reactivation of type-2 immune responses leading to smooth muscle contraction and mucus hypersecretion-physiological processes very similar to acute exacerbations in the airways following allergen exposure. In this study, we employed a murine model of intestinal helminth infection, using Heligmosomoides polygyrus, to identify miRNAs during active expulsion, as a system for the identification of miRNAs that may contribute to AE in the airways. Concomitant with type-2 immunity and expulsion of H. polygyrus, we identified miR-99a-5p, miR-148a-3p and miR-155-5p that were differentially regulated. Systemic inhibition of these miRNAs, alone or in combination, had minimal impact on expulsion of H. polygyrus, but inhibition of miR-99a-5p or miR-155-5p significantly reduced house dust mite (HDM)-driven acute inflammation, modelling human acute exacerbations. Immunological, pathological and transcriptional analysis identified that miR-155-5p or miR-99a-5p contribute significantly to HDM-driven AE and that transient inhibition of these miRNAs may provide relief from allergen-driven AE, without compromising anti-helminth immunity in the gut.


Subject(s)
Allergens/immunology , Asthma/etiology , Immunologic Memory , MicroRNAs/genetics , Animals , Asthma/metabolism , Asthma/pathology , Biomarkers , Disease Progression , Disease Susceptibility , Gene Expression Profiling , Helminthiasis, Animal/complications , Helminthiasis, Animal/immunology , Helminthiasis, Animal/parasitology , Host-Parasite Interactions , Immunity, Innate , Mice
10.
Noncoding RNA ; 6(1)2020 Mar 06.
Article in English | MEDLINE | ID: mdl-32155783

ABSTRACT

Immunological diseases, including asthma, autoimmunity and immunodeficiencies, affect a growing percentage of the population with significant unmet medical needs. As we slowly untangle and better appreciate these complex genetic and environment-influenced diseases, new therapeutically targetable pathways are emerging. Non-coding RNA species, which regulate epigenetic, transcriptional and translational responses are critical regulators of immune cell development, differentiation and effector function, and may represent one such new class of therapeutic targets. In this review we focus on type-2 immune responses, orchestrated by TH2 cell-derived cytokines, IL-4, IL-5 and IL-13, which stimulate a variety of immune and tissue responses- commonly referred to as type-2 immunity. Evolved to protect us from parasitic helminths, type-2 immune responses are observed in individuals with allergic diseases, including Asthma, atopic dermatitis and food allergy. A growing number of studies have identified the involvement of various RNA species, including microRNAs (miRNA) and long non-coding (lncRNA), in type-2 immune responses and in both clinical and pre-clinical disease settings. We highlight these recent findings, identify gaps in our understanding and provide a perspective on how our current understanding can be harnessed for novel treat opportunities to treat type-2 immune-mediated diseases.

11.
J Oral Maxillofac Surg ; 67(11): 2460-5, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19837318

ABSTRACT

PURPOSE: Piezoelectric surgery (PES) uses a modulated ultrasonic frequency that permits highly precise and safe hard tissue cutting. A retrospective study on a series of spiral family implants inserted with or without PES split crest was performed to verify if implants inserted into crests split using PES have a comparable outcome to those inserted into unsplit bone. MATERIAL AND METHODS: In the period from May 2004 to November 2007, 86 patients (55 women and 31 men, median age 53 yrs) were operated on and 234 spiral family implants were inserted. Among these, 21 were inserted into PES split crest. Mean follow-up was 13 months (3 to 35 months). The Kaplan-Meier algorithm was used to compare the 2 groups in survival and clinical success (ie, decreased bone resorption around implant neck). RESULTS: Only 9 of 234 implants were lost (ie, survival rate 96.2%), all of which belonged to the unsplit group but no statistical difference was demonstrated. To detect if PES split crest produces a better clinical outcome in comparison with fixtures inserted into unsplit alveolar ridges, crestal bone loss was compared in the remaining loaded implants (234--9 lost--5 not prosthetized = 220). No statistical significant difference was detected by comparing implants inserted into PES split crests with untreated alveolar ridges, although a better trend was visible for fixtures inserted into PES split crests. CONCLUSION: PES split crests provide several advantages and clinical outcomes that are not worse in terms of bone remodeling, if compared with standard procedures.


Subject(s)
Alveolar Ridge Augmentation/methods , Dental Implantation, Endosseous/methods , Dental Implants , Oral Surgical Procedures/instrumentation , Osseointegration , Osteotomy/instrumentation , Alveolar Process/diagnostic imaging , Alveolar Process/surgery , Alveolar Ridge Augmentation/instrumentation , Bone Remodeling/physiology , Dental Implantation, Endosseous/instrumentation , Dental Prosthesis Design , Dental Restoration Failure , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Oral Surgical Procedures/methods , Osteotomy/methods , Radiography , Treatment Outcome , Ultrasonics
12.
J Oral Maxillofac Surg ; 67(2): 387-93, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19138615

ABSTRACT

PURPOSE: In the last decade, several investigators reported that standard-diameter implants (SDIs) achieved excellent results. However, no report is available regarding SDIs inserted into fresh-frozen bone (FFB). We conducted a retrospective study on a series of SDIs (diameter, 3.75 mm) inserted into homologous FFB to evaluate their clinical outcome. MATERIALS AND METHODS: The SDIs inserted with FFB were analyzed. Several variables were investigated regarding patients, anatomic sites, implants, and prosthetic restoration. Implant failure and peri-implant bone resorption were considered predictors of clinical outcome. A Kaplan-Meier algorithm and Cox regression were performed to detect those variables statistically associated with clinical outcomes. RESULTS: One hundred thirty-three SDIs were inserted in 41 patients. Implant length ranged from 10 to 15 mm. Implants were inserted to replace 6 incisors, 13 cuspids, 60 premolars, and 54 molars. The mean follow-up was 23 months. Only 1 of 133 implants was lost (ie, survival rate=99.2%), and no differences were detected among study variables. On the contrary, crestal bone resorption correlates with type of prosthetic restoration, with a better outcome for removable dentures. CONCLUSION: The SDIs had high survival and success rates, similar to those reported in previous studies of 2-stage procedures in nongrafted bone. The SDIs inserted into FFB are reliable, although a greater marginal bone loss is to be expected if fixed prosthetic restorations are used.


Subject(s)
Alveolar Ridge Augmentation/methods , Bone Transplantation/methods , Dental Implantation, Endosseous/methods , Dental Implants , Cryopreservation , Dental Prosthesis Design , Female , Humans , Kaplan-Meier Estimate , Male , Maxillary Sinus/surgery , Middle Aged , Proportional Hazards Models , Retrospective Studies , Treatment Outcome
13.
J Craniofac Surg ; 20(1): 24-8, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19164983

ABSTRACT

Condylar fractures (CFs) are about 30% of mandibular fractures. Condylar fractures are treated with several protocols, and unsatisfying outcome is achieved in some cases. A staging system for classifying CFs is of paramount importance to plan therapy, to define prognosis, and to exchange information among trauma centers. The Strasbourg Osteosynthesis Research Group proposed a classification system for CFs, but no report focusing to its effectiveness is still available. Thus, we performed a retrospective study on a series of patients affected by CFs.The Strasbourg Osteosynthesis Research Group classification defines 3 main types of CFs: diacapitular fracture (i.e., through the head of the condyle [DF]), fracture of the condylar neck, and fracture of the condylar base (CBF). A series of 66 patients (and 84 CFs) was evaluated, and age, sex, clinical diagnosis at admission, treatment, and outcome were considered.Fractures of the condylar base and DFs are the most (52.4%) and the least (4.8%) frequent fractures, respectively. Conversely, associated fractures of the facial skeleton are found in most cases of DFs (75%) and in few cases of CBFs (20.5%). Surgery was performed in about 15% of all cases: no DF was operated, whereas fractures of the condylar neck and CBFs have an open reduction and an internal rigid fixation in 57% and 43%, respectively. Postsurgical and late sequelae were 22.3% and 19%. Temporomandibular joint symptoms and malocclusion cover about 80% and 90% of postsurgical and late sequelae.The new classification is a simple method to define CFs and can give some elements about the prognosis.


Subject(s)
Mandibular Condyle/injuries , Mandibular Fractures/classification , Adolescent , Adult , Aged , Cartilage, Articular/injuries , Child , Child, Preschool , Facial Bones/injuries , Female , Fracture Fixation/statistics & numerical data , Fracture Fixation, Internal/statistics & numerical data , Humans , Italy/epidemiology , Joint Capsule/injuries , Joint Dislocations/epidemiology , Male , Malocclusion/epidemiology , Mandibular Condyle/pathology , Mandibular Fractures/epidemiology , Middle Aged , Postoperative Complications/epidemiology , Prognosis , Retrospective Studies , Skull Fractures/epidemiology , Temporomandibular Joint Disorders/epidemiology , Treatment Outcome , Young Adult
14.
Implant Dent ; 18(3): 270-8, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19509537

ABSTRACT

PURPOSE: In the last 2 decades, several investigators have reported immediate placement of dental implants into extraction sockets achieving excellent results with a 2-stage surgical procedure. Recently, immediate loading has become an emerging technique as it has been documented to be a successful and a time saving procedure. As regard, few reports are available for the possibility of immediate/early loading of implants placed in fresh extraction sockets. In addition, they are based on limited series with short follow-up. Thus, we decided to perform a retrospective study on a series of postextractive spiral family implants (SFIs). MATERIALS AND METHODS: In the period May 2004 to November 2007, 133 SFIs were inserted in fresh extraction sockets. The mean follow-up was 12 months. Several host-, surgery-, and implant-related factors were investigated and Kaplan-Meier algorithm and Cox regression were used to detect those variables associated with the clinical outcome. RESULTS: Because only 7 of 133 implants were lost (i.e., survival rate, 94.7%) and no statistical differences were detected among the studied variables, no, or reduced, marginal bone loss was considered as an indicator of success rate to evaluate the effect of several host-, surgery-, and implants-related factors. Also, in this case no variable has impact on clinical outcome. CONCLUSION: It was demonstrated that postextractive SFIs have a high survival and success rate that are similar to those reported in previous studies of 2-stage procedures or in immediate loading implants inserted in healed bone.


Subject(s)
Dental Implantation, Endosseous/methods , Dental Implants, Single-Tooth , Dental Prosthesis Design , Tooth Socket/surgery , Adult , Aged , Alveolar Bone Loss/etiology , Dental Implants, Single-Tooth/adverse effects , Dental Prosthesis, Implant-Supported , Dental Restoration Failure , Dental Stress Analysis , Denture, Partial, Immediate , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Time Factors
15.
Cell Tissue Bank ; 10(3): 227-33, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19048393

ABSTRACT

In the case of severe jaw atrophy several options are available to restore the alveolar crest. Aim of the present study was to evaluate the resorption over time of homologous fresh frozen bone used to restore the alveolar ridge. Specifically factors influencing (1) graft survival, (2) type, and (3) degree of bone resorption were evaluated. One hundred and thirteen maxillae and 27 mandibles were grafted. The surgical techniques used were 102 inlay, 27 onlay, and 11 veneer. Measurements were taken on pre-operative, post-operative, and follow-up radiographs. Data were processed by using three statistical methods: Kaplan-Meier algorithm, Cox regression, and curve estimation. As regards graft survival, Cox regression output showed a statistically significant effect only on surgical technique (P = 0.0312) and Kaplan-Meier algorithm demonstrated a worse outcome for veneer surgical technique (Log rank test = 0.0242). The Curve estimation demonstrated an inverse correlation between degree of bone resorption over time, with a progressive decrease. In conclusion FFB is a reliable material for alveolar bone restoration with a predicable average of resorption.


Subject(s)
Alveolar Ridge Augmentation/methods , Freezing , Ilium/transplantation , Mandibular Diseases/surgery , Maxillary Diseases/surgery , Tissue Preservation , Atrophy , Bone Resorption/pathology , Bone Transplantation , Female , Graft Survival/physiology , Humans , Ilium/physiology , Kaplan-Meier Estimate , Male , Mandibular Diseases/pathology , Maxillary Diseases/pathology , Middle Aged , Proportional Hazards Models , Retrospective Studies , Transplantation, Homologous
16.
Implant Dent ; 18(1): 86-95, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19212241

ABSTRACT

In the last decade several studies have been performed to evaluate the clinical outcome of implants inserted into grafted mandibles with autologous bone, but none is available on mandibles grafted with fresh-frozen bone. Thus, we planned a retrospective study on a series of implants inserted into homologue fresh-frozen bone to evaluate their clinical outcome. Twenty-one patients were operated on, 28 onlay grafts were inserted into the mandible, and 63 implants placed. Patients had total and partial edentulism in 11 and 10 cases, respectively. The mean follow-up was 20 months. No or reduced crestal bone resorption was considered an indicator of success rate to evaluate the effect of several host-, implant-, and occlusal-related factors. The difference between the implant-abutment junction and the bone crestal level was defined as the implant abutment junction (IAJ) and calculated at the time of operation and during follow-up by means of radiographs. Delta IAJ, the difference between theIAJ at the last check-up and the IAJ recorded just after the operation, were stratified according to variables of interests. Kaplan-Meier algorithm and Cox regression were then performed to detect those variables statistically associated with the delta IAJ. Only 2 of 63 implants were lost (i.e., survival rates = 96.8%) and no differences were detected among the studied variables. On the contrary, Cox regression showed that prosthetic restoration (i.e., removable dentures) was the only factor correlated with a statistically significant lower delta IAJ (i.e., reduced crestal bone loss) and thus a better clinical outcome. Implants inserted into mandibles grafted with fresh-frozen bone allografts have high survival rates and success rate, which are comparable with those obtained with autologous iliac crest bone grafts.


Subject(s)
Bone Transplantation/methods , Cryopreservation/methods , Mandible/surgery , Tissue Preservation/methods , Alveolar Bone Loss/etiology , Alveolar Bone Loss/surgery , Alveolar Ridge Augmentation/methods , Dental Abutments , Dental Implants , Dental Prosthesis, Implant-Supported , Dental Restoration Failure , Female , Follow-Up Studies , Humans , Jaw, Edentulous/surgery , Jaw, Edentulous, Partially/surgery , Male , Middle Aged , Osseointegration/physiology , Retrospective Studies , Surgical Wound Infection/etiology , Treatment Outcome
17.
J Oral Implantol ; 35(4): 176-80, 2009.
Article in English | MEDLINE | ID: mdl-19813421

ABSTRACT

In the last decade, some investigations have reported that the resorbable blast media surface (also named CaPO4 blasted implants [CaPO4-Bls]) has achieved excellent results. However, no report regarding CaPO4-Bls inserted into fresh frozen bone (FFB) is available. Thus, we planned a retrospective study on a series of CaPO4-Bls inserted into FFB to evaluate their clinical outcome. In the period between December 2003 and December 2006, 16 patients (10 females and 6 males, median age of 55 years) were operated on, and 76 CaPO4-Bls were inserted. The mean implant follow-up was 23 months. Implant diameter and length ranged from 3.25 to 4.5 mm and from 11.5 to 15 mm, respectively. Implants were inserted to replace 7 incisors, 11 cuspids, 31 premolars, and 27 molars. Only 1 out of 76 implants was lost (i.e., survival rate [SVR] = 98.7%), and no differences were detected among the studied variables. When peri-implant crestal bone resorption was used as an indicator of clinical success (i.e., success rate), it was possible to identify some variables that correlated with a better clinical outcome. Specifically, Cox regression showed that removable prosthetic restoration and longer implant length correlated with a statistically significant lower delta implant abutment junction (IAJ; i.e., reduced crestal bone loss) and thus a better clinical outcome. In this study, CaPO4-Bls had high survival and success rates, similar to those reported in previous reports of 2-stage procedures in nongrafted bone. CaPO4-Bls inserted into FFB are reliable devices, although greater marginal bone loss occurs when fixed prosthetic restorations and short implants are used.


Subject(s)
Alveolar Ridge Augmentation/methods , Bone Transplantation/methods , Calcium Phosphates/chemistry , Coated Materials, Biocompatible/chemistry , Dental Implants , Dental Prosthesis Design , Alveolar Bone Loss/etiology , Cryopreservation , Dental Implantation, Endosseous/methods , Dental Materials/chemistry , Dental Prosthesis, Implant-Supported , Dental Restoration Failure , Female , Follow-Up Studies , Humans , Ilium , Male , Mandible/surgery , Maxilla/surgery , Middle Aged , Retrospective Studies , Surface Properties , Survival Analysis , Titanium/chemistry , Transplantation, Homologous , Treatment Outcome
18.
J Contemp Dent Pract ; 10(5): E049-56, 2009 Sep 01.
Article in English | MEDLINE | ID: mdl-19838610

ABSTRACT

AIM: Spiral family implants (SFIs) are a new type of implant fixture with a conical internal helix and a variable thread design. The aim of this retrospective study was to evaluate the clinical outcomes of a series of SFIs. METHODS AND MATERIALS: A total of 234 SFIs were placed in 86 patients (55 females and 31 males, median age 53 years) during the period between May 2004 and November 2007. The mean follow-up was 13 months. Several host, surgery, and implant-related factors were investigated, and the Kaplan Meier algorithm and the Cox regression were used to detect variables associated with the clinical outcome. RESULTS: Only nine out of 234 implants were lost (i.e., survival rate (SVR) of 96.2%) and no differences were detected among the studied variables. CONCLUSION: SFIs have a high SVR similar to those reported in previous studies on different implant types. CLINICAL SIGNIFICANCE: SFIs demonstrated a very high primary stability which offers the potential for use of a specific implant device for immediate loading. However, additional studies are necessary to verify their outcome on the medium/long period.


Subject(s)
Dental Implantation, Endosseous/instrumentation , Dental Implants, Single-Tooth , Dental Prosthesis Design , Dental Restoration Failure , Dental Implantation, Endosseous/methods , Dental Restoration, Permanent/instrumentation , Dental Restoration, Permanent/methods , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Mandible , Maxilla , Middle Aged , Outcome Assessment, Health Care , Retrospective Studies
19.
Stomatologija ; 10(4): 127-32, 2008.
Article in English | MEDLINE | ID: mdl-19223712

ABSTRACT

OBJECTIVE: In the last decade, several investigators have reported that standard length implants (SLIs) have achieved excellent results but no report regarding SLIs (i.e. SLI, length=13 mm) inserted into alveolar bone sites previously augmented with frozen bone (FB) is available. The aim of this study was to evaluate the clinical outcome of SLIs inserted into alveolar bone sites previously augmented with FB. PATIENTS AND METHODS: The survival and success rate of standard dental implants was evaluated after surgical placement into alveolar bone sites previously augmented with FB. The distance between Implant Abutment Junction and crestal bone level (i.e. delta IAJ) was measured to evaluate the peri-implant bone loss over time. Kaplan-Meier algorithm and Cox regression were used. RESULTS: The implant survival rate was 97.6% and no differences were detected among the studied variables by using implant loss. On the contrary, the Cox regression showed that implant surface (i.e. sandblasted and acid-etched-SLA- and CaPO(4)ceramic-blasted implants, p=0.0037), graft site (i.e. maxilla, p=0.0438) and prosthetic restoration (i.e. removable dentures, p=0.0003) correlated with a statistically significant reduced crestal bone loss (i.e. success rate). CONCLUSION: SLIs had a high survival and success rate similar to those reported in previous studies of two-stage procedures in non-grafted bone. FB is a reliable material for alveolar reconstruction and implant insertion.


Subject(s)
Alveolar Ridge Augmentation/methods , Bone Transplantation/methods , Dental Implantation, Endosseous , Dental Implants , Dental Prosthesis, Implant-Supported , Alveolar Bone Loss/etiology , Dental Implants/adverse effects , Dental Prosthesis Design , Dental Restoration Failure , Denture, Complete , Female , Follow-Up Studies , Freezing , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models
20.
Dent Res J (Isfahan) ; 9(Suppl 2): S175-80, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23814579

ABSTRACT

BACKGROUND: The concept of osseointegration, i.e., the direct anchorage of endosseous implants made of commercially pure or titanium alloy to the bone caused a breakthrough in oral rehabilitation. The identification of factors for long-term survival and success rate are the main goal of the recent literature. Several variables can influence the final result, and in general they are grouped in surgery-, host-, implant-, and occlusion-related factors. MATERIALS AND METHODS: A retrospective analysis on a large series of dental implants was performed to detect those variables influencing the clinical outcome. In the period between January 2007 and December 2009, 157 patients were operated. A total of 429 implants were inserted. Dental implants are reliable devices to be used in oral rehabilitation. RESULTS: Globally, very few implants were lost at the end of the follow-up period. Slight but significant differences existed among different implants types with regard to peri-implant bone resorption. CONCLUSION: A better clinical outcome was revealed for Sweden and Martina global implant.

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