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1.
Int J Implant Dent ; 4(1): 13, 2018 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-29696470

RESUMEN

BACKGROUND: The aim of this study was to assess surface characteristics, element composition, and surface roughness of five different commercially available dental zirconia implants. Five zirconia implants (Bredent whiteSKY™ (I1), Straumann® PURE Ceramic (I2), ceramic.implant vitaclinical (I3), Zeramex® (I4), Ceralog Monobloc M10 (I5)) were evaluated. METHODS: The evaluation was performed by means of scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and confocal laser scanning microscopy (CLSM). RESULTS: The semi-quantitative element composition showed no significant impurity of any implant tested. Both the machined and the rough areas of the investigated implants were predominated by zirconium, oxygen, and carbon. Roughness values (Sa) showed highest values for I2 and I5. CONCLUSIONS: The investigated zirconia implants showed surface characteristics and roughness values close to those of conventionally produced titanium implants, making them a promising alternative. However, zirconia implants have yet to prove themselves in clinical practice and clinical controlled trials.

2.
Int J Implant Dent ; 3(1): 36, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28748521

RESUMEN

BACKGROUND: The augmentation of the jaw has been and continues to be a sophisticated therapy in implantology. Modern CAD-CAM technologies lead to revival of old and established augmentation techniques such as the use of titanium mesh (TM) for bone augmentation. The aim of this retrospective study was to evaluate the clinical outcome of an individualized CAD-CAM-produced TM based on the CT/DVT-DICOM data of the patients for the first time. METHODS: In 17 patients, 21 different regions were augmented with an individualized CAD-CAM-produced TM (Yxoss CBR®, Filderstadt, Germany). For the augmentation, a mixture of autologous bone and deproteinized bovine bone mineral (DBBM) or autologous bone alone was used. Reentry with explantation of the TM and simultaneous implantation of 44 implants were performed after 6 months. Preoperative and 6-month postoperative cone beam computed tomographies (CBCT) were performed to measure the gained bone height. RESULTS: The success rate for the bone grafting procedure was 100%. Thirty-three percent of cases presented an exposure of the TM during the healing period. However, premature removal of these exposed meshes was not necessary. Exposure rate in augmentations performed with mid-crestal incisions was higher than in augmentations performed with a modified poncho incision (45.5 vs. 20%, p = 0.221). In addition, exposure rates in the maxilla were significantly higher than in the mandible (66.7 vs. 8.3%, p = 0.009). Gender, smoking, periodontal disease, gingiva type, used augmentation material, and used membrane had no significant influence on the exposure rate (p > 0.05). The mean vertical augmentation was 6.5 ± 1.7 mm, and the mean horizontal augmentation was 5.5 ± 1.9 mm. Implant survival rate after a mean follow-up of 12 ± 6 months after reentry was 100%. CONCLUSION: Within the limits of the retrospective character of this study, this study shows for the first time that individualized CAD-CAM TM provide a sufficient and safe augmentation technique, especially for vertical and combined defects. However, the soft tissue handling for sufficient mesh covering remains one of the most critical steps using this technique.

3.
Int J Implant Dent ; 3(1): 10, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28353194

RESUMEN

BACKGROUND: The aim of this study was to measure the oral health-related quality of life (OHRQoL) after maxillary sinus augmentation to determine the physical and psychological impact of this procedure for the patient. METHODS: Three hundred sixteen patients treated with an external or internal maxillary sinus augmentation and a total of 863 implants in the Department of Oral and Maxillofacial Surgery, Johannes Gutenberg University, Mainz, Germany, between July 2002 and December 2007 were included in this retrospective study. Total implant survival was assessed. Completion of a modified 26-item version of the Oral Health Impact Profile (OHIP-G) for assessing the oral health-related quality of life before and after the treatment was asked for. Subcategories were (1) functional limitations, (2) physical and psychological disabilities, and (3) complaints due to the surgical procedure. In 53 patients available for clinical follow-up examination, assessment of soft tissue parameters was performed. RESULTS: After an average time in situ of 41.2 ± 27 months (3.4 years), the in situ rate was 95.4%. One-year survival rate and five-year survival rate according to Kaplan Meier were 95.4 and 94.4%. Concerning functional limitations, significant better values for OHRQoL after sinus augmentation procedure than before the treatment (p < 0.001) were seen. In the subcategory physical and psychological disabilities, all questions had significant better values after the sinus lift (p < 0.001). Concerning complaints due to the surgical procedure, mean total scores were 5.1 ± 5.4 pre-operative, 6.9 ± 6.1 (0-31) post-operative, and 2.4 ± 3.7 recently. This meant a significant difference between "pre-operative" vs. "post-operative" (p = 0.003), "pre-operative" vs. "recently" (p < 0.001), and "post-operative" vs. "recently" (p < 0.001). Concerning the influence of implant indication, edentulous patients showed the most distinct improvement after the procedure. Clinical assessment showed stable soft tissue parameters. CONCLUSIONS: Evaluation of OHRQoL after sinus augmentation showed a significant improvement indicating a remarkable benefit for the patients through this procedure.

4.
Clin Oral Investig ; 21(1): 397-403, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27020911

RESUMEN

OBJECTIVES: The purpose of this clinical prospective, randomized, double-blind trial was to compare the anesthetic efficacy of 2 % articaine and 4 % articaine in inferior alveolar nerve block anesthesia for extraction of mandibular teeth. MATERIALS AND METHODS: In 95 patients, 105 lower molar and premolar teeth were extracted after intraoral inferior alveolar nerve block. In 53 cases, 2 % articaine (group I) and, in 52 cases, 4 % articaine (group II) was administered. The primary objective was to analyze the differences of anesthetic effects between the two groups (complete/sufficient vs. insufficient/none). Furthermore, differences in pulpal anesthesia (onset and depth, examined with pulp vitality tester (min)), as well as in length of soft tissue anesthesia (min), were evaluated. Additionally, the need of a second injection, pain while injecting (numeric rating scale (NRS)), pain during treatment (NRS), pain after treatment (NRS), and other possible complications (excessive pain, bleeding events, prolonged deafness) were analyzed. RESULTS: Anesthesia was sufficient for dental extractions in both groups without significant differences (p = 0.201). The onset of anesthesia did not differ significantly (p = 0.297). A significantly shorter duration of soft tissue anesthesia was seen in group I (2.9 vs. 4 h; p < 0.001). There was no significant difference in the need for a second injection (p = 0.359), in injection pain (p = 0.386), as well as in pain during (p = 0.287) or after treatment (p = 0.121). In both groups, no complications were seen. CONCLUSIONS: The local anesthetic effect of the 4 % articaine solution is not significantly better when compared to 2 % articaine. CLINICAL RELEVANCE: For mandibular tooth extraction, articaine 2 % may be used as alternative as well.


Asunto(s)
Anestésicos Locales/administración & dosificación , Carticaína/administración & dosificación , Bloqueo Nervioso/métodos , Extracción Dental , Método Doble Ciego , Femenino , Humanos , Masculino , Nervio Mandibular , Dimensión del Dolor , Estudios Prospectivos , Resultado del Tratamiento
5.
Clin Oral Implants Res ; 28(6): 721-726, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27172991

RESUMEN

AIM: Clinical studies evaluating the influence of the implant design on the preservation of peri-implant keratinized mucosa are rare. The aim of this prospective multicenter study was to investigate the survival, and soft and hard tissue maintenance of an implant with a sloped shoulder configuration, when placed in the posterior mandible. MATERIAL AND METHODS: In this study, 24 centers participated and 184 patients receiving 238 implants (OsseoSpeed™ Profile TX implants) were included. Clinical assessments of soft tissue parameters were performed before implant placement, immediately after implant placement, at prosthetic delivery and at 6, 12 and 24 months after implant placement and marginal bone adaptation was examined. RESULTS: After an average time in situ of 28.7 ± 4.7 months (2.4 ± 0.4 years), the survival rate was 99.2%. Analysis of the peri-implant soft tissues during follow-up showed a slight but significant increase in peri-implant keratinized mucosa width after 2 years (P < 0.001). All patients with reduced peri-implant keratinized mucosa width of ≤ 2 mm at postoperative examination (n = 95) showed a pronounced and statistically significant increase in the peri-implant keratinized mucosa width over time (P < 0.001). After a mean follow-up of 20.7 ± 8 months (1.7 ± 0.7 years), mean inter-proximal marginal bone loss was 0.30 ± 0.6 mm, indicating high bone stability around the sloped implant neck. CONCLUSION: These results indicate that sloped configurated implants have a high survival rate after 2 years in function. The sloped implant shoulder configuration helps to support the hard and soft tissue around the implant neck and supports the regain of a physiological peri-implant keratinized mucosa in patients with compromised peri-implant soft tissue conditions (Clinicaltrials.gov: NCT01400321).


Asunto(s)
Proceso Alveolar/fisiología , Implantes Dentales , Diseño de Prótesis Dental , Mucosa Bucal/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Queratinas , Masculino , Mandíbula/fisiología , Persona de Mediana Edad , Estudios Prospectivos , Análisis de Supervivencia , Extracción Dental
6.
Biomaterials ; 77: 207-15, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26606446

RESUMEN

Artificial generated buccal mucosa equivalents are a promising approach for the reconstruction of urethral defects. Limiting in this approach is a poor blood vessel supply after transplantation, resulting in increased morbidity and necrosis. We generated a pre-vascularized buccal mucosa equivalent in a tri-culture of primary buccal epithelial cells, fibroblasts and microvascular endothelial cells, using a native collagen membrane as a scaffold. A successful pre-vascularization and dense formation of capillary-like structures at superficial areas was demonstrated. The lumen size of pre-formed blood vessels corresponded to the capillary size in vivo (10-30 µm). Comparing native with a highly cross-linked collagen membrane we found a distinct higher formation of capillary-like structures on the native membrane, apparently caused by higher secretion of angiogenic factors such as PDGF, IL-8 and angiopoietin by the cells. These capillary-like structures became functional blood vessels through anastomosis with the host vasculature after implantation in nude mice. This in vitro method should result in an accelerated blood supply to the biomaterial with cells after transplantation and increase the succes rates of the implant material.


Asunto(s)
Células Endoteliales/citología , Células Epiteliales/citología , Fibroblastos/citología , Mucosa Bucal , Organoides/irrigación sanguínea , Ingeniería de Tejidos/métodos , Trasplantes/irrigación sanguínea , Inductores de la Angiogénesis/análisis , Animales , Capilares/citología , Capilares/crecimiento & desarrollo , Células Cultivadas , Técnicas de Cocultivo , Colágeno , Prepucio/citología , Encía/citología , Xenoinjertos , Humanos , Masculino , Membranas Artificiales , Ratones , Ratones Desnudos , Organoides/citología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/análisis , Andamios del Tejido
9.
Eur J Dent Educ ; 19(1): 16-22, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24646115

RESUMEN

INTRODUCTION: To evaluate the impact of experience whilst using different devices for intraligamentary anaesthesia, dental students tested clinical anaesthetic efficacy of a mechanical (PDL-S) and a computer-controlled (CCLAD) application system in restorative patients. MATERIAL AND METHODS: In a prospective study, 41 Patients in need of restorative treatment in lower posterior mandible were randomised into three groups (PDL-S: teeth n = 22; CCLAD: teeth n = 20; inferior alveolar nerve block (IANB): teeth n = 20). Dental last year students conducted anaesthesia and dental treatment. Primary objectives were differences in pain during treatment [numeric rating scale (NRS)] as well as in anaesthetic efficacy (complete/sufficient vs. insufficient/no effect) between PDL-S and CCLAD. Pain of injection, need for second injections, amount of anaesthetic solution and duration of local numbness were assessed. IANB as gold standard was compared to each system descriptively. RESULTS: PDL-S had a significant lower pain during treatment (P = 0.017) but a similar anaesthetic efficacy (P = 0.175) compared to the CCLAD system. Concerning pain of injection (P = 0.42), quantity of second injections (P = 0.232), amount of used solution (P = 0.073) as well as duration of local numbness (P = 0.253), no differences were seen. When comparing both periodontal ligament injection (PDL)-systems with IANB, pain rating was higher when using CCLAD. Injection pain, amount of used solution as well as soft tissue anaesthesia was less for PDL-S and CCLAD. DISCUSSION: Both PDL techniques showed a good success for dental routine treatments. Although, compared to the mechanic device, the CCLAD system might need more clinical daily experience. CONCLUSION: We recommend including specific trainings in intraligamentary anaesthesia in the dental curriculum.


Asunto(s)
Anestesia Dental/instrumentación , Anestesia Local/instrumentación , Anestésicos Locales/administración & dosificación , Carticaína/administración & dosificación , Competencia Clínica , Ligamento Periodontal , Jeringas , Estudios de Casos y Controles , Humanos , Inyecciones , Mandíbula , Dimensión del Dolor , Estudios Prospectivos
10.
Clin Oral Investig ; 18(3): 687-98, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24271500

RESUMEN

OBJECTIVES: The aim of this comprehensive literature review is to provide recommendations and guidelines for dental implant therapy in patients with a history of radiation in the head and neck region. For the first time, a meta-analysis comparing the implant survival in irradiated and non-irradiated patients was performed. MATERIAL AND METHODS: An extensive electronic search in the electronic databases of the National Library of Medicine was conducted for articles published between January 1990 and January 2013 to identify literature presenting survival data on the topic of dental implants in patients receiving radiotherapy for head and neck cancer. Review and meta-analysis were performed according to Preferred Reporting Items for Systematic Review and Meta-Analyses statement. For meta-analysis, only studies with a mean follow-up of at least 5 years were included. RESULTS: After screening 529 abstracts from the electronic database, we included 31 studies in qualitative and 8 in quantitative synthesis. The mean implant survival rate of all examined studies was 83 % (range, 34-100 %). Meta-analysis of the current literature (2007-2013) revealed no statistically significant difference in implant survival between non-irradiated native bone and irradiated native bone (odds ratio [OR], 1.44; confidence interval [CI], 0.67-3.1). In contrast, meta-analysis of the literature of the years 1990-2006 showed a significant difference in implant survival between non-irradiated and irradiated patients ([OR], 2.12; [CI], 1.69-2.65) with a higher implant survival in the non-irradiated bone. Meta-analysis of the implant survival regarding bone origin indicated a statistically significant higher implant survival in the irradiated native bone compared to the irradiated grafted bone ([OR], 1.82; [CI], 1.14-2.90). CONCLUSIONS: Within the limits of this meta-analytic approach to the literature, this study describes for the first time a comparable implant survival in non-irradiated and irradiated native bone in the current literature. Grafted bone combined with radiotherapy was identified as a negative prognostic factor on implant survival. CLINICAL RELEVANCE: The evolution of implant hardware and improvement of treatment strategies during the last years have affirmed dental implant-supported concepts as a valuable treatment option for patients with a history of radiation in the head and neck region.


Asunto(s)
Implantes Dentales , Neoplasias de Cabeza y Cuello/radioterapia , Falla de Prótesis , Neoplasias de Cabeza y Cuello/fisiopatología , Humanos
11.
Oral Maxillofac Surg ; 17(1): 53-7, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22527654

RESUMEN

BACKGROUND: Hodgkin lymphoma (HL) are lymphoproliferative neoplasms, histologically comprising of mononuclear and multinucleated Hodgkin and Reed Sternberg cells (HRS). About 4 % of all lymphatic malignancies of the head and neck are HL. The typical disease presents itself as a nodal lesion. Extranodal, enoral soft tissue involvement by HL is very rare. CASE REPORT: A 73-year-old man with a suspect, ulcerating lesion in the left retromolar region of the mandible was assigned to our hospital. Prior anti-inflammatory therapy has been without success. Subsequently, three biopsies were taken which could only show inflammation. Finally, two biopsies from the left retromolar region and the left inner cheek showed HRS cells with positive expressions of CD15 and CD30 corresponding to a Hodgkin lymphoma. No lymphatic node or bone involvement could be detected. The patient was designated to receive radio-chemotherapy, but died 3 weeks after diagnosis of multiple organ failure. In a literature review, together with this report, nine cases were found concerning primary HL of the oral mucosa. Accordingly, this is the first case of primary multiple extranodal HL in the oral mucosa in absence of lymphatic node involvement. DISCUSSION: Neither clinical features nor radiological appearances of HL presenting as primary enoral lesions are pathognomonic. Especially when only small biopsy specimens are available, histological diagnosis remains challenging, may lead to a delay in therapy and may result in a significant worse prognosis.


Asunto(s)
Enfermedad de Hodgkin/diagnóstico , Neoplasias Mandibulares/diagnóstico , Neoplasias de la Boca/diagnóstico , Anciano , Biopsia , Resultado Fatal , Enfermedad de Hodgkin/patología , Humanos , Masculino , Neoplasias Mandibulares/patología , Mucosa Bucal/patología , Neoplasias de la Boca/patología , Células de Reed-Sternberg/patología
12.
Clin Oral Implants Res ; 24(11): 1222-30, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22762383

RESUMEN

OBJECTIVES: Combinations of bone substitute block materials with membrane techniques as well as with growth factors are possible options to enhance the prognosis of vertical bone augmentation. Therefore, the aim of the pilot study was to compare the influence of a collagen membrane and a signal protein (rhPDGF-BB) on vertical bone augmentation with a stable fixed block material (deproteinized bovine bone [DBB]). MATERIALS AND METHODS: In 12 rabbits, a DBB-block was implant-fixed on the tibia in a split-leg-design. Included were: DBB only (control), DBB + collagen membrane (test), DBB + rhPDGF-BB (test) and DBB + rhPDGF-BB + collagen membrane (test). 24 samples were examined after 3 (n = 12) and 6 weeks (n = 12). Calculated parameters were new bone area (NBA;%), new vertical bone height (VBH; mm). Due to the pilot character of this study, single values are shown descriptively only. RESULTS: After 3 weeks, there were constant higher NBA values in the rhPDGF-BB-group without membrane (NBA (%) DBB: 30/16/4; DBB + membrane: 25/17/7, DBB + rhPDGF-BB: 40/33/34, DBB + rhPDGF-BB + membrane: 0/30/16; VBH (mm) DBB: 1.2/1.2/1, DBB + membrane: 0.7/0.9/1, DBB + rhPDGF-BB: 0.7/0.9/1, DBB + rhPDGF-BB + membrane: 0/1.1/1). After 6 weeks, both membrane groups showed a constant higher NBA and VBH independent to the use of rhPDGF-BB (NBA DBB: 3/0/5, DBB + membrane: 20/35/31, DBB + rhPDGF-BB: 5/8/4, DBB + rhPDGF-BB + membrane: 31/35/40; VBH DBB: 0.3/0.3/0.6, DBB + membrane: 1.6/2.4/2.1, DBB + rhPDGF-BB: 0.4/0.7/0.8, DBB + rhPDGF-BB + membrane: 1.8/2/1.8). CONCLUSIONS: For vertical augmentation, the addition of rhPDGF-BB to DBB-blocks may increase early bone growth. In the later phase, the use of a collagen membrane enhances new bone volume and height to a significant greater extend. Even if the results are higher than those in the non-membrane groups, the low gain of bone after the short time periods still needs improvement.


Asunto(s)
Aumento de la Cresta Alveolar/métodos , Sustitutos de Huesos/farmacología , Colágeno/farmacología , Implantes Dentales , Proteínas Proto-Oncogénicas c-sis/farmacología , Animales , Becaplermina , Regeneración Ósea , Bovinos , Proyectos Piloto , Estudios Prospectivos , Conejos
13.
J Oral Pathol Med ; 42(5): 374-81, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23227881

RESUMEN

INTRODUCTION: Functional polymorphisms (SNPs) of the vascular endothelial growth factor (VEGF) are associated with the incidence of oral squamous cell carcinoma (OSCC). An impact of VEGF-SNPs on prognosis of OSCC patients seems possible. Therefore, correlations between prognostic parameters of OSCC patients and five VEGF-SNPs were determined. MATERIALS AND METHODS: In a retrospective long-term study, in 113 OSCC patients that underwent curative resections, five VEGF-SNPs (-1154 G/A, +405 G/C, +936 C/T, -2578 C/A, and -460 C/T) were analyzed. Associations between SNPs and prognosis (incidence of local recurrent disease, second cancer, metastases, death, total disease-free survival) were examined. RESULTS: After a mean follow-up time of 57.6 months, 32 patients had local recurrences; 15 patients had second cancer, 15 patients metastases, and 23 patients died. The mean disease-free survival was 43.1 months. A significant increased incidence of OSCC in smokers with the VEGF -2578 A/C and -460 C/T SNP was seen (each P < 0.0001). In univariate analysis, patients with advanced OSCCs (T > 2 or N > 0) together with the -1154 A/A allele had a significant worse survival and a worse disease-free survival (both P < 0.04). The same was seen for the +405 G/G SNP (both P = 0.002). In multivariate analysis, only the negative influence of the +405 G/G SNP on survival in advanced OSCCs (T > 2) could be confirmed (P = 0.002). DISCUSSION: Possible reciprocal interactions between smoking and VEGF-SNP function were observed. Multivariate analysis confirmed the VEGF +405 G/G genotype to be associated with poor survival in advanced OSCCs; a further use of this haplotype as biomarker has to be discussed.


Asunto(s)
Carcinoma de Células Escamosas/cirugía , Neoplasias de la Boca/cirugía , Polimorfismo de Nucleótido Simple/genética , Factor A de Crecimiento Endotelial Vascular/genética , Adenosina , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/secundario , Citosina , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Frecuencia de los Genes/genética , Genotipo , Guanina , Haplotipos , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/genética , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias Primarias Secundarias/patología , Pronóstico , Estudios Retrospectivos , Fumar , Tasa de Supervivencia , Timina , Adulto Joven
14.
Oral Oncol ; 48(7): 608-14, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22341306

RESUMEN

Growth-differentiation factor 15 (GDF 15) is involved in tumor pathogenesis and its expression is increased in many types of cancers. Functional effects of GDF 15 on oncogenesis of oral squamous cell carcinoma (OSCC) remain unclear. Therefore, the aim of this study was to examine the apoptotic characteristics of GDF 15 in OSCC cell lines in vitro and to analyze serum GDF 15 concentrations as a diagnostic and prognostic tumor marker for OSCC in vivo. Caspase activity was assessed in OSCC cell lines with the Caspase-Glo 3/7 system. Serum GDF 15 concentrations from 64 patients with histopathological proven OSCC and from 30 healthy volunteers were measured using an enzyme-linked immunosorbent assay. In 21 patients, serum GDF 15 was also analyzed postoperatively. In vitro, treatment of OSCC cell lines with GDF 15 reduced Caspase 3/7 activity significantly (p<0.05). In vivo, serum GDF 15 concentrations of the OSCC patients in all stages of OSCC were significantly higher than those of the healthy subjects (p<0.0001). After surgery, GDF 15 concentrations declined significantly from 1545±774pg/ml preoperative to 953±438pg/ml postoperative (p=0.003). The median survival time of OSCC patients with GDF 15 levels below 875pg/ml was significantly higher than of OSCC patients with GDF 15 levels above or equal 875pg/ml (p=0.031). Determination of receiver operating characteristic curves (ROC) showed a respective area under the ROC curve (AUC) of 0.943. The anti-apoptotic effect of GDF 15 in OSCC cell lines was shown in vitro. In vivo, significant elevated serum GDF 15 levels with prognostic value in OSCC-patients were seen for the first time. The results indicate that GDF15 may be used as a potential marker for diagnosis and prognosis of this entity.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/sangre , Caspasas/metabolismo , Factor 15 de Diferenciación de Crecimiento/sangre , Neoplasias de la Boca/sangre , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Estudios de Casos y Controles , Línea Celular Tumoral , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Pronóstico
15.
J Cell Physiol ; 224(1): 120-6, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20232299

RESUMEN

Growth differentiation factor 15 (GDF15) is induced during heart failure development, and may influence different processes in cardiac remodeling. While its anti-apoptotic action under conditions of ischemia-reperfusion have been shown, it remained unclear if this is a broadly protective effect applicable to other apoptotic stimuli. Furthermore, effects on cardiac hypertrophy remained obscure. Therefore, we investigated the effects of GDF15 on induction of hypertrophy and apoptosis in ventricular cardiomyocytes. GDF15 (3 ng/ml) enhanced hypertrophic growth of cardiomyocytes as determined by an increase in cell size by 27 +/- 5% and rate of protein synthesis by 47 +/- 15%. In addition, a time and dose-dependent increase in SMAD-binding affinity was found, as well as enhanced phosphorylation of R-SMAD1. Inhibition of SMADs by transformation of cardiomyocytes with SMAD-decoy oligonucleotides abolished the hypertrophic growth effect. Specific inhibitors of PI3K (10 microM LY290042 or 10 nM wortmannin) or ERK (10 microM PD98059) also blocked GDF15-induced hypertrophy and SMAD activation. Apoptosis induction by three different agents, 100 nM angiotensin II, 1 ng/ml TGFbeta(1), or the NO-donor SNAP (100 microM) was blocked by addition of GDF15 (3 ng/ml). Scavenging of SMADs by transformation of cardiomyocytes with SMAD-decoy oligonucleotides abolished the anti-apoptotic effect of GDF15. In conclusion, GDF15 protects ventricular cardiomyocytes against different apoptotic stimuli and enhances hypertrophic growth. Hypertrophic signaling is thereby mediated via the kinases PI3K and ERK and the transcription factor R-SMAD1. Thus, GDF15 may influence cardiac remodeling via two different mechanisms, apoptosis protection and induction of hypertrophy.


Asunto(s)
Apoptosis , Cardiomegalia/metabolismo , Cardiomegalia/patología , Factor 15 de Diferenciación de Crecimiento/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Transducción de Señal , Factores de Edad , Angiotensina II/metabolismo , Animales , Apoptosis/efectos de los fármacos , Cardiomegalia/prevención & control , Células Cultivadas , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Masculino , Miocitos Cardíacos/efectos de los fármacos , Donantes de Óxido Nítrico/farmacología , Oligonucleótidos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Fosforilación , Inhibidores de Proteínas Quinasas/farmacología , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Proteína Smad1/genética , Proteína Smad1/metabolismo , Factores de Tiempo , Factor de Crecimiento Transformador beta1/metabolismo , Remodelación Ventricular
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