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1.
Cell Rep ; 42(12): 113515, 2023 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-38096048

RESUMO

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.


Assuntos
MicroRNAs , Precursores de RNA , Animais , Camundongos , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Receptores de Imidazolinas/genética , Receptores de Imidazolinas/metabolismo , Mamíferos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Interferência de RNA , Precursores de RNA/genética , Precursores de RNA/metabolismo , Splicing de RNA/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
2.
Sci Transl Med ; 14(641): eabl8146, 2022 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-35442706

RESUMO

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.


Assuntos
Asma , Fatores de Crescimento de Fibroblastos , Corticosteroides/farmacologia , Corticosteroides/uso terapêutico , Animais , Fluticasona/farmacologia , Fluticasona/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Ácido Hialurônico , Inflamação/tratamento farmacológico , Camundongos
3.
Sci Transl Med ; 14(627): eabf8188, 2022 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-35020406

RESUMO

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.


Assuntos
Asma , Oncostatina M/metabolismo , Animais , Asma/patologia , Humanos , Pulmão/patologia , Macrófagos/metabolismo , Camundongos , Muco , Oncostatina M/genética
4.
Mucosal Immunol ; 14(4): 912-922, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33846533

RESUMO

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.


Assuntos
Alérgenos/imunologia , Asma/etiologia , Memória Imunológica , MicroRNAs/genética , Animais , Asma/metabolismo , Asma/patologia , Biomarcadores , Progressão da Doença , Suscetibilidade a Doenças , Perfilação da Expressão Gênica , Helmintíase Animal/complicações , Helmintíase Animal/imunologia , Helmintíase Animal/parasitologia , Interações Hospedeiro-Parasita , Imunidade Inata , Camundongos
5.
Noncoding RNA ; 6(1)2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32155783

RESUMO

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.

6.
PLoS Pathog ; 12(4): e1005528, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27055274

RESUMO

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.


Assuntos
Infecções Assintomáticas , Doenças Transmissíveis/microbiologia , Mutagênicos/toxicidade , Salmonella typhimurium/patogenicidade , Febre Tifoide/microbiologia , Animais , Intestinos/microbiologia , Macrófagos/microbiologia , Camundongos , Virulência
7.
Proc Natl Acad Sci U S A ; 113(5): E568-76, 2016 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-26787865

RESUMO

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.


Assuntos
Hipersensibilidade/imunologia , Proteínas Nucleares/fisiologia , Receptores de Interleucina-1/metabolismo , Células Th2/imunologia , Fatores de Transcrição/fisiologia , Animais , Helmintos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Nucleares/genética , Células Th2/metabolismo , Fatores de Transcrição/genética
8.
Cell Microbiol ; 15(12): 2034-50, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23869968

RESUMO

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.


Assuntos
Toxinas Bacterianas/metabolismo , Salmonella typhi/metabolismo , Salmonella typhimurium/metabolismo , Vesículas Secretórias/metabolismo , Sequência de Aminoácidos , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Toxinas Bacterianas/genética , Brefeldina A/farmacologia , Células CACO-2 , Linhagem Celular , Dano ao DNA , Dinamina I/antagonistas & inibidores , Dinamina I/metabolismo , Dinaminas/antagonistas & inibidores , Endocitose , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Células HeLa , Humanos , Hidrazonas/farmacologia , Camundongos , Regiões Promotoras Genéticas , Salmonella typhi/genética , Salmonella typhi/patogenicidade , Salmonella typhimurium/genética , Salmonella typhimurium/patogenicidade
9.
Cell Microbiol ; 15(1): 98-113, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22998585

RESUMO

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.


Assuntos
Toxinas Bacterianas/metabolismo , Dano ao DNA/efeitos dos fármacos , Instabilidade Genômica/efeitos dos fármacos , Bactérias Gram-Negativas/patogenicidade , Mutagênicos/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Humanos , Ratos
10.
Dent Res J (Isfahan) ; 9(Suppl 2): S175-80, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23814579

RESUMO

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.

11.
Toxins (Basel) ; 3(3): 172-90, 2011 03.
Artigo em Inglês | MEDLINE | ID: mdl-22069704

RESUMO

The cytolethal distending toxins (CDTs), produced by a variety of Gram-negative pathogenic bacteria, are the first bacterial genotoxins described, since they cause DNA damage in the target cells. CDT is an A-B(2) toxin, where the CdtA and CdtC subunits are required to mediate the binding on the surface of the target cells, allowing internalization of the active CdtB subunit, which is functionally homologous to the mammalian deoxyribonuclease I. The nature of the surface receptor is still poorly characterized, however binding of CDT requires intact lipid rafts, and its internalization occurs via dynamin-dependent endocytosis. The toxin is retrograde transported through the Golgi complex and the endoplasmic reticulum, and subsequently translocated into the nuclear compartment, where it exerts the toxic activity. Cellular intoxication induces DNA damage and activation of the DNA damage responses, which results in arrest of the target cells in the G1 and/or G2 phases of the cell cycle and activation of DNA repair mechanisms. Cells that fail to repair the damage will senesce or undergo apoptosis. This review will focus on the well-characterized aspects of the CDT biology and discuss the questions that still remain unanswered.


Assuntos
Toxinas Bacterianas/toxicidade , Núcleo Celular/efeitos dos fármacos , Dano ao DNA , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Toxinas Bacterianas/química , Toxinas Bacterianas/genética , Linhagem Celular , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Colite/etiologia , Colite/imunologia , Colite/microbiologia , Endocitose/efeitos dos fármacos , Bactérias Gram-Negativas/metabolismo , Bactérias Gram-Negativas/patogenicidade , Humanos , Neoplasias/etiologia , Neoplasias/imunologia , Neoplasias/microbiologia , Periodontite/etiologia , Periodontite/imunologia , Periodontite/microbiologia , Ligação Proteica , Subunidades Proteicas , Fatores de Virulência/química , Fatores de Virulência/genética , Fatores de Virulência/toxicidade
12.
J Cell Sci ; 124(Pt 16): 2735-42, 2011 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-21807938

RESUMO

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.


Assuntos
Toxinas Bacterianas/metabolismo , Sobrevivência Celular , Citoesqueleto/metabolismo , Endonucleases Flap/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Actinas/metabolismo , Toxinas Bacterianas/genética , Sobrevivência Celular/genética , Biologia Computacional , Citoesqueleto/ultraestrutura , Dano ao DNA , Reparo do DNA/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Endocitose/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Endonucleases Flap/genética , Células HeLa , Humanos , Saccharomyces cerevisiae/genética , Deleção de Sequência/genética , Transdução de Sinais/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transgenes/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
FEBS J ; 278(23): 4577-88, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21585655

RESUMO

Cytolethal distending toxin, produced by several Gram-negative bacteria, and colibactin, secreted by several commensal and extraintestinal pathogenic Escherichia coli strains, are the first bacterial genotoxins to be described to date. Exposure to cytolethal distending toxin and colibactin induces DNA damage, and consequently activates the DNA damage response, resulting in cell cycle arrest of the intoxicated cells and DNA repair. Irreversible DNA damage will lead to cell death by apoptosis or to senescence. It is well established that chronic exposure to DNA damaging agents, either endogenous (reactive oxygen species) or exogenous (ionizing radiation), may cause genomic instability as a result of the alteration of genes coordinating the DNA damage response, thus favoring tumor initiation and progression. In this review, we summarize the state of the art of the biology of cytolethal distending toxin and colibactin, focusing on the activation of the DNA damage response and repair pathways, and discuss the cellular responses induced in intoxicated cells, as well as how prolonged intoxication may lead to chronic inflammation, the accumulation of genomic instability, and tumor progression in both in vitro and in vivo models.


Assuntos
Toxinas Bacterianas/metabolismo , Instabilidade Genômica , Inflamação/metabolismo , Mutagênicos/metabolismo , Neoplasias/metabolismo , Animais , DNA/metabolismo , Dano ao DNA , Reparo do DNA , Humanos , Inflamação/etiologia , Modelos Biológicos , Neoplasias/etiologia , Peptídeos/metabolismo , Policetídeos/metabolismo
14.
PLoS One ; 5(1): e8924, 2010 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-20111719

RESUMO

BACKGROUND: The MYC protein controls cellular functions such as differentiation, proliferation, and apoptosis. In response to genotoxic agents, cells overexpressing MYC undergo apoptosis. However, the MYC-regulated effectors acting upstream of the mitochondrial apoptotic pathway are still unknown. PRINCIPAL FINDINGS: In this study, we demonstrate that expression of Myc is required to activate the Ataxia telangiectasia mutated (ATM)-dependent DNA damage checkpoint responses in rat cell lines exposed to ionizing radiation (IR) or the bacterial cytolethal distending toxin (CDT). Phosphorylation of the ATM kinase and its downstream effectors, such as histone H2AX, were impaired in the myc null cell line HO15.19, compared to the myc positive TGR-1 and HOmyc3 cells. Nuclear foci formation of the Nijmegen Breakage Syndrome (Nbs) 1 protein, essential for efficient ATM activation, was also reduced in absence of myc. Knock down of the endogenous levels of MYC by siRNA in the human cell line HCT116 resulted in decreased ATM and CHK2 phosphorylation in response to irradiation. Conversely, cell death induced by UV irradiation, known to activate the ATR-dependent checkpoint, was similar in all the cell lines, independently of the myc status. CONCLUSION: These data demonstrate that MYC contributes to the activation of the ATM-dependent checkpoint responses, leading to cell death in response to specific genotoxic stimuli.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Dano ao DNA , Proteínas de Ligação a DNA/metabolismo , Genes myc , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Proteínas Mutadas de Ataxia Telangiectasia , Divisão Celular , Linhagem Celular , Técnicas de Silenciamento de Genes , Fosforilação , RNA Interferente Pequeno , Ratos
15.
Clin Implant Dent Relat Res ; 12(2): 91-8, 2010 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-19076178

RESUMO

BACKGROUND: Several studies have been performed to evaluate the clinical outcome of implants inserted into maxillae grafted with autogenous bone but few reports have focused on maxillae grafted with fresh-frozen allogenous bone (FFAB). PURPOSE: The purpose of this study is to retrospectively evaluate the clinical outcome of implants installed in resorbed maxillae augmented with FFAB. MATERIALS AND METHODS: A total of 69 patients whom had been treated with FFAB grafts to their maxillae and implant placement 4 to 6 months later were retrospectively evaluated. Edentulism was total and partial in 22 and 47 cases, respectively. A total of 287 implants of various systems had been used. A life table analysis was performed. Marginal bone loss was calculated in radiographs. RESULTS: Five of the 287 implants were lost, giving a survival rate (SVR) of 98.3% over a mean follow-up time of 26 months. The marginal bone resorption at the implants was 1.68 mm (SD = 0.44) after 1 year and 1.85 mm (SD = 0.98) after 4 years. The cumulative success rate based on defined criteria was 96% in the first year but decreased to 40% at 4 years because of marginal bone loss. The Kaplan-Meier algorithm demonstrated a better outcome for female patients, removable dentures, and total edentulism. No differences were detected among diameters, lengths, and implant site. CONCLUSION: Implants placed in FFAB showed a high SVR similar to that reported in previous studies on maxillae grafted with autogenous iliac crest bone. Although our data point to more marginal bone loss in partially edentulous patients and for fixed prosthetic restorations, the use of FFAB for reconstruction of the atrophic jaw prior to implant placement can be considered as a reliable alternative to autogenous bone.


Assuntos
Perda do Osso Alveolar/reabilitação , Aumento do Rebordo Alveolar/métodos , Transplante Ósseo/métodos , Implantação Dentária Endóssea , Arcada Edêntula/reabilitação , Perda do Osso Alveolar/diagnóstico por imagem , Planejamento de Prótese Dentária , Prótese Dentária Fixada por Implante , Falha de Restauração Dentária , Feminino , Congelamento , Humanos , Estimativa de Kaplan-Meier , Tábuas de Vida , Masculino , Doenças Maxilares/reabilitação , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Radiografia , Estudos Retrospectivos , Doadores de Tecidos
16.
J Oral Maxillofac Surg ; 67(11): 2460-5, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19837318

RESUMO

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.


Assuntos
Aumento do Rebordo Alveolar/métodos , Implantação Dentária Endóssea/métodos , Implantes Dentários , Procedimentos Cirúrgicos Bucais/instrumentação , Osseointegração , Osteotomia/instrumentação , Processo Alveolar/diagnóstico por imagem , Processo Alveolar/cirurgia , Aumento do Rebordo Alveolar/instrumentação , Remodelação Óssea/fisiologia , Implantação Dentária Endóssea/instrumentação , Planejamento de Prótese Dentária , Falha de Restauração Dentária , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Bucais/métodos , Osteotomia/métodos , Radiografia , Resultado do Tratamento , Ultrassom
17.
J Contemp Dent Pract ; 10(5): E049-56, 2009 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-19838610

RESUMO

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.


Assuntos
Implantação Dentária Endóssea/instrumentação , Implantes Dentários para Um Único Dente , Planejamento de Prótese Dentária , Falha de Restauração Dentária , Implantação Dentária Endóssea/métodos , Restauração Dentária Permanente/instrumentação , Restauração Dentária Permanente/métodos , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Mandíbula , Maxila , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos
18.
J Oral Implantol ; 35(4): 176-80, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19813421

RESUMO

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.


Assuntos
Aumento do Rebordo Alveolar/métodos , Transplante Ósseo/métodos , Fosfatos de Cálcio/química , Materiais Revestidos Biocompatíveis/química , Implantes Dentários , Planejamento de Prótese Dentária , Perda do Osso Alveolar/etiologia , Criopreservação , Implantação Dentária Endóssea/métodos , Materiais Dentários/química , Prótese Dentária Fixada por Implante , Falha de Restauração Dentária , Feminino , Seguimentos , Humanos , Ílio , Masculino , Mandíbula/cirurgia , Maxila/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Propriedades de Superfície , Análise de Sobrevida , Titânio/química , Transplante Homólogo , Resultado do Tratamento
19.
J Appl Oral Sci ; 17(4): 301-6, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19668989

RESUMO

OBJECTIVE: Narrow diameter implants (NDI) (i.e. diameter <3.75 mm) are a potential solution for specific clinical situations, such as reduced interradicular bone, thin alveolar crest and replacement of teeth with small cervical diameter. NDI have been available in clinical practice since the 1990s, but only few studies have analyzed their clinical outcome and no study have investigated NDI inserted in fresh-frozen bone (FFB) grafts. Thus, a retrospective study on a series of NDI placed in homologue FFB was designed to evaluate their clinical outcome. MATERIAL AND METHODS: In the period between December 2003 and December 2006, 36 patients (22 females and 14 males, mean age 53 years) with FFB grafts were selected and 94 different NDI were inserted. The mean follow-up was 25 months. To evaluate the effect of several host-, surgery-, and implant-related factors, marginal bone loss (MBL) was considered an indicator of success rate (SCR). The Kaplan Meier algorithm and Cox regression were used. RESULTS: Only 5 out of 94 implants were lost (i.e. survival rate - SVR 95.7%) and no differences were detected among the studied variables. On the contrary, the Cox regression showed that the graft site (i.e. maxilla) reduced MBL. CONCLUSIONS: NDI inserted in FFB have a high SVR and SCR similar to those reported in previous studies on regular and NDI inserted in non-grafted jaws. Homologue FFB is a valuable material in the insertion of NDI.


Assuntos
Implantes Dentários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
20.
J. appl. oral sci ; 17(4): 301-306, July/Aug. 2009. ilus, tab
Artigo em Inglês | LILACS | ID: lil-521705

RESUMO

OBJECTIVE: Narrow diameter implants (NDI) (i.e. diameter <3.75 mm) are a potential solution for specific clinical situations, such as reduced interradicular bone, thin alveolar crest and replacement of teeth with small cervical diameter. NDI have been available in clinical practice since the 1990s, but only few studies have analyzed their clinical outcome and no study have investigated NDI inserted in fresh-frozen bone (FFB) grafts. Thus, a retrospective study on a series of NDI placed in homologue FFB was designed to evaluate their clinical outcome. MATERIAL AND METHODS: In the period between December 2003 and December 2006, 36 patients (22 females and 14 males, mean age 53 years) with FFB grafts were selected and 94 different NDI were inserted. The mean follow-up was 25 months. To evaluate the effect of several host-, surgery-, and implant-related factors, marginal bone loss (MBL) was considered an indicator of success rate (SCR). The Kaplan Meier algorithm and Cox regression were used. RESULTS: Only 5 out of 94 implants were lost (i.e. survival rate - SVR 95.7 percent) and no differences were detected among the studied variables. On the contrary, the Cox regression showed that the graft site (i.e. maxilla) reduced MBL. CONCLUSIONS: NDI inserted in FFB have a high SVR and SCR similar to those reported in previous studies on regular and NDI inserted in non-grafted jaws. Homologue FFB is a valuable material in the insertion of NDI.


Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Implantes Dentários , Resultado do Tratamento
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