RESUMO
PURPOSE: There is a lack of knowledge about drug-related problems (DRPs) among pregnant and lactating women. The aim of this study was to determine the extent and type of DRPs among pregnant and lactating women in the maternity ward at two Norwegian hospitals. We also aimed to investigate which drugs were involved in the identified DRPs, and the outcome of solving the DRPs. METHODS: Patient-reported treatment reviews were performed to assess the prevalence and type of DRPs among women at the two maternity wards. RESULTS: In all, 212 women were included in the study, of which 89 (42 %) had experienced at least one DRP (105 DRPs in total). "Need for additional drug" (49 cases, 46.7 %) was the most frequent. The most frequent drug group involved in DRPs was drugs acting on the respiratory system, and the most common intervention was raising awareness/providing confidence/giving information during the patient-reported treatment review. CONCLUSIONS: Over four out of ten women in the maternity wards have DRPs, and many have questions about drug use during pregnancy and lactation. Many of the DRPs could probably be avoided by providing patient-reported treatment reviews to pregnant women as a part of antenatal care. Multidisciplinary collaboration including physicians, midwifes, and pharmacists in antenatal care and in maternity ward could possibly prevent DRPs and thereby promote patient safety for pregnant and lactating women.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Unidade Hospitalar de Ginecologia e Obstetrícia/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Interações Medicamentosas , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Prescrição Inadequada , Lactação , Erros de Medicação , Noruega/epidemiologia , Cooperação do Paciente , Gravidez , Adulto JovemRESUMO
BACKGROUND: Several different procedures have been described for surgical treatment of rectal prolapse and consensus on the optimal approach has not been reached. The Swedish Rectal Prolapse Trial was performed with the aim to compare the outcomes after the most common surgical approaches to rectal prolapse. METHOD: A multicentre randomized trial was conducted from 2000 to 2009. Patients were randomized between a perineal or an abdominal approach for correction of rectal prolapse (randomization A) if eligible for any procedures. Patients considered unsuitable for random allocation were only included in randomizations B or C. Patients in randomization B (perineal group) were randomized to Delorme's or Altemeier's procedures and those in randomization C (abdominal group) to suture rectopexy or resection rectopexy. Primary outcomes were bowel function and quality of life, measured using Wexner incontinence score and RAND-36, and secondary outcomes were complications and recurrence at 3 years. RESULTS: During the study period, 134 patients were randomized: 18 in randomization A group, 80 in randomization B group and 54 in randomization C group; of these, 122 patients underwent surgery. Mean follow-up was 2.6 years. Improvements in Wexner and RAND-36 scores were seen but with no significant difference between the groups. Health change scores were significantly improved from baseline up to 1 year after surgery (P < 0.001). At 3 years, recurrence rates were two of seven patients for abdominal versus five of eight patients for perineal approach (P = 0.315), 18 of 31 patients (58 per cent) for Delorme's versus 15 of 30 patients (50 per cent) for Altemeier's (P = 0.611) and four of 19 patients (21 per cent) for suture rectopexy versus two of 21 patients (10 per cent) for resection rectopexy (P = 0.398). There were no significant differences regarding postoperative complications. CONCLUSION: For all procedures, significant improvements from baseline in health change scores were noted after surgery. Recurrence rates were higher than previously reported. Registration number: NCT04893642 (http://www.clinicaltrials.gov).
Assuntos
Incontinência Fecal , Prolapso Retal , Incontinência Fecal/etiologia , Humanos , Recidiva Local de Neoplasia , Qualidade de Vida , Prolapso Retal/cirurgia , Reto/cirurgiaRESUMO
The purpose of the study was to estimate in vitro material degradation in implants and cobalt-chrome or titanium frameworks, before and after exposure to artificial saliva. Four full-arch implant frameworks were fabricated according to the Cresco™ method (Astra Tech AB, Mölndal, Sweden), two in a cobalt-chrome alloy and two in commercially pure (CP) titanium. They were cut vertically, and the three central sections of each framework were used. Element leakage into an artificial saliva solution was observed with mass spectrometry. Before artificial saliva exposure, three Brånemark System(®) implants (Nobel Biocare AB, Gothenburg, Sweden) were screw-retained to cobalt-chrome sections, and three to titanium sections. The contact surfaces with the implants of the framework sections and the corresponding surfaces of six implants were examined with optical interferometry before and after exposure to artificial saliva to evaluate material degradation. Conventional descriptive statistics were used to present the mass spectrometry and interferometry data. One-way anova and Dunnett's T3 post hoc test were used to identify and study differences between the groups. To highlight changes within the groups, the Student's t-test was used. The significance level was set at 5%. There was significantly more leakage of cobalt elements than of titanium and chrome (P < 0·05). After saliva exposure and framework connection, the implants roughened (P < 0·05). The titanium frameworks were generally rougher than the cobalt-chrome frameworks, both before and after saliva exposure (P < 0·05). The findings in this study suggest active material degradation processes for both implants and framework materials.
Assuntos
Ligas de Cromo/química , Cobalto/química , Implantes Dentários , Titânio/química , Análise de Variância , Falha de Restauração Dentária , Interferometria , Teste de Materiais , Saliva/química , Propriedades de SuperfícieRESUMO
A fixed partial denture is preferred as a prosthetic restoration supported by tissue-integrated oral implants. However, there are occasions, especially in restoring an edentulous maxilla, when a fixed partial denture does not satisfy a patient's requirements for esthetics, good phonetics, proper oral hygiene, and oral comfort. A removable hybrid prosthesis attached to a bar that is conventionally fixed to tissue-integrated implants ad modum Brånemark was therefore designed to satisfy such needs and to meet requirements for splinting of the implants. Following the placement of prostheses, patients were asked to give their opinion on the comfort, phonetics, and esthetics of the prosthesis by marking a visual analog scale. The results indicate a successful initial outcome of the treatment.
Assuntos
Implantes Dentários , Planejamento de Dentadura , Revestimento de Dentadura , Adulto , Idoso , Estética Dentária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , FalaRESUMO
Maxillary prosthetic restorations on osseointegrated implants are often problematic because of implant location, orientation, and need for lip support. A new design for a hybrid maxillary prosthesis that will provide good esthetics and phonetics, as well as ensure optimum conditions for oral hygiene and patient comfort, is proposed. The design includes separate support, lateral stabilization, and retention. Support is derived from elevated areas at the midline and on the extensions of a bar screwed to dental implants ad modum Brånemark. Lateral stabilization is obtained by a removable framework closely fitting the bar. Four precision attachments provide adjustable retention without influencing support. Technical aspects of the procedure are described.
Assuntos
Implantação Dentária Endóssea , Planejamento de Dentadura , Prótese Total Superior , Revestimento de Dentadura , Encaixe de Precisão de Dentadura , Humanos , Maxila , OsseointegraçãoRESUMO
The aim of this 3-year prospective study was to evaluate the prosthetic treatment in 2 groups of maxillary edentulous patients with similar age and gender distribution: a study group of 39 patients treated with intra-sinus block bone grafts and implants in a 1-stage procedure, and a control (reference) group of 37 patients treated with implants and no grafting. In the study group, bone volumes were regarded as insufficient for implant treatment unless a bone grafting procedure was performed (posterior alveolar bone height was less than 5 mm). Self-tapping Nobel Biocare implants were used in both groups of patients. In the study group, 35 fixed partial dentures and 4 overdentures were placed, and in the control group 34 fixed partial dentures and 3 overdentures were placed. All patients were followed for at least 3 years. The 3-year follow-up examination included examination of a number of clinical parameters as well as the type of abutment and evaluation of stability of prosthesis retention screws and abutment screws. During the follow-up period, 2 patients were lost from the study group and 4 patients from the control group, giving a total of 70 patients available for examination after 3 years (8% dropout rate). Both the amount of plaque and gingival bleeding were significantly lower in the study group than in the control group. The presence of attached gingiva was 25% in the study group and 35% in the control group. The number of angulated abutments was significantly higher in the study group than in the control group. There was no significant difference in the number of prosthetic complications in the 2 groups of patients. Neither was there any significant difference in prosthesis screw or abutment screw stability between the 2 groups. The type of abutment did not significantly influence the stability of prosthesis retention screws or abutment screws in either of the groups. However, prosthesis screw stability was significantly greater than abutment screw stability in both groups of patients. It can be concluded that the prosthetic outcome was similar in the 2 groups of patients, regardless of whether or not a bone grafting procedure was used.
Assuntos
Aumento do Rebordo Alveolar/métodos , Implantação Dentária Endóssea , Implantes Dentários , Maxila/cirurgia , Seio Maxilar/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Atrofia , Transplante Ósseo , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Dente Suporte , Placa Dentária/classificação , Planejamento de Prótese Dentária , Retenção em Prótese Dentária , Prótese Dentária Fixada por Implante , Revestimento de Dentadura , Prótese Parcial Fixa , Feminino , Seguimentos , Gengiva/patologia , Hemorragia Gengival/classificação , Humanos , Arcada Edêntula/reabilitação , Arcada Edêntula/cirurgia , Arcada Parcialmente Edêntula/reabilitação , Arcada Parcialmente Edêntula/cirurgia , Masculino , Pessoa de Meia-Idade , Osseointegração , Estudos Prospectivos , Estatística como Assunto , Resultado do TratamentoRESUMO
This 3-year follow-up study compares implant treatment in 39 1-stage sinus-inlay block-grafted patients (study group) with 37 patients treated without bone grafting (reference group), all of whom were edentulous in the maxilla and were treated over the same time period. The cumulative success rate (CSR) of implant stability after 3 years in the study group was 75.3% in grafted areas and 82.2% in non-grafted areas. The CSR after 3 years in the reference group was 93.1%. The mean marginal bone resorption after 3 years of loading was 1.4 mm in grafted areas and 1.6 mm in non-grafted areas in the study group and 1.1 mm in the reference group. Complications noted during the postoperative healing periods correlated significantly with implant failures later on (P < .05). Since prosthesis stability (CSR) after 3 years was 94.9% in the study group and 97.3% in the reference group, it can be concluded that 1-stage sinus-inlay block grafts can be regarded as a safe method with a predictable outcome for use on patients with severely atrophied edentulous maxillae, although increased failure rates are to be expected for implants placed in bone-grafted regions.
Assuntos
Transplante Ósseo/métodos , Implantes Dentários , Falha de Restauração Dentária , Seio Maxilar/cirurgia , Procedimentos Cirúrgicos Pré-Protéticos Bucais/métodos , Idoso , Idoso de 80 Anos ou mais , Perda do Osso Alveolar/cirurgia , Estudos de Casos e Controles , Implantação Dentária Endóssea/métodos , Feminino , Seguimentos , Humanos , Arcada Edêntula/reabilitação , Tábuas de Vida , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Osseointegração , Complicações Pós-Operatórias , Estudos Prospectivos , Resultado do TratamentoRESUMO
Eighty consecutive patients, referred to the Department of Prosthetic Dentistry, Public Dental Service, Stockholm, for examination of complaints related to dental restorative materials or for supposed adverse effects from mercury released from dental amalgams were investigated. Clinical examination as well as battery of laboratory tests were performed. Statistical correlations were found between subjective and objective oral symptoms and lowered pH-values in stimulated saliva (p less than 0.001) as well as between objective oral symptoms only and lowered pH-values in stimulated saliva (p less than 0.001), which indicate salivary tests to be a useful tool when examining this type of patients.
Assuntos
Amálgama Dentário/efeitos adversos , Restauração Dentária Permanente/efeitos adversos , Doenças da Boca/complicações , Doenças das Glândulas Salivares/complicações , Fumar/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Saúde , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Saliva/metabolismo , Saliva/fisiologia , Taxa Secretória , Testes CutâneosRESUMO
This study comprised a clinical and radiological examination of two groups of 14 patients receiving overdentures of the same design on osseointegrated implants. The mean follow-up period was 82 months and 35 months in the two groups the fixture success rate was 84% and 85% and the marginal bone loss 0.97 mm and 1.29 mm respectively. The follow-up of the two groups was guided by several clinical parameters and apart from the loss of fixtures and adjustments of the attachment system only a few complications were registered. The results show that this treatment method is a successful alternative in the treatment of the edentulous maxillae.
Assuntos
Prótese Dentária Fixada por Implante , Revestimento de Dentadura , Idoso , Idoso de 80 Anos ou mais , Perda do Osso Alveolar/diagnóstico por imagem , Implantação Dentária Endóssea , Retenção de Dentadura/instrumentação , Seguimentos , Humanos , Maxila , Pessoa de Meia-Idade , Osseointegração , Avaliação de Resultados em Cuidados de Saúde , Projetos Piloto , RadiografiaAssuntos
Implantação Dentária Endóssea , Implantes Dentários , Prótese Total Superior , Revestimento de Dentadura , Idoso , Idoso de 80 Anos ou mais , Bactérias/isolamento & purificação , Sulfatos de Condroitina/análise , Dente Suporte , Planejamento de Dentadura , Feminino , Seguimentos , Líquido do Sulco Gengival/química , Humanos , Ácido Hialurônico/análise , Masculino , Pessoa de Meia-Idade , Osseointegração , Doenças Periodontais/etiologia , Periodonto/metabolismo , Periodonto/microbiologia , Estresse MecânicoRESUMO
Since single-tooth implant restorations were introduced 12 years ago (Jemt 1986), there has been continuous development both in the technical design and the aesthetic outcome of the treatment. In order to ensure high quality in single-tooth implant treatments a clinical follow-up study was carried out on patients treated with modifications to the original regimen. In this study 69 consecutive patients were provided with 80 single-tooth implant restorations. The patients were followed for 3 years. There was continuous development of the prosthetic design during the time of the study, allowing us to analyse possible prognostic differences for the different prosthetic treatments. This study confirms earlier reports which describe the single-tooth implant treatment as a safe method with few surgical complications and minimal marginal bone loss. Only 1 implant was lost during the follow-up period and the average marginal bone loss was 0.48 mm over the 3-year follow-up period. Crowns veneered with acrylic and with gold casted directly to the abutments, screwed onto the implants, led to recurring prosthetic complications and gave an appearance of rapid ageing. The first generation of crowns made following the Cera-One design, sometimes produced a gap between the crown and the abutment associated with significant marginal bone loss during the first year. Few surgical or prosthetic complications were noted with cemented all-ceramic constructions, although the number of these crowns in this study was limited.
Assuntos
Implantes Dentários para Um Único Dente , Planejamento de Prótese Dentária , Adolescente , Adulto , Idoso , Perda do Osso Alveolar/etiologia , Distribuição de Qui-Quadrado , Coroas , Dente Suporte , Implantação Dentária Endóssea , Implantes Dentários para Um Único Dente/efeitos adversos , Porcelana Dentária , Humanos , Masculino , Ligas Metalo-Cerâmicas , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Estatísticas não ParamétricasRESUMO
Previous studies have indicated that examination of glycosaminoglycans (GAG) present in peri-implant sulcus fluid (PISF) may be a useful indicator of metabolic activity of the supporting bone. The GAG content in PISF from osseointegrated implants ad modum Brånemark in the maxilla was quantified and analysed. The study comprised 2 groups with 10 patients in each group. In one group the patients wore removable prostheses; in group 2 the patients wore fixed prostheses. The groups were matched for age, sex and function period of their prosthetic appliances. Clinical data were recorded, and the levels of the GAG hyaluronan (HA) and chondroitin-4-sulphate (C4S) were assessed using cellulose acetate electrophoresis and densitometric scanning of Alcian blue-stained strips against known GAG standards. PISF volumes and levels of C4S as potential bone marker showed no significant difference (both groups median 0.003 microgram). There was a somewhat higher median value for HA (0.015 microgram) in the group of patients with removable prostheses compared with the group with fixed prosthesis (HA = 0.008 micrograms) (NS). HA is known to be present in high amounts in gingival tissue. As both plaque index and gingival bleeding were more frequent in patients with removable prostheses, this may be the reason for the somewhat higher value for HA in this group of patients. The difference in biomechanical properties of fixed and removable prostheses on implants do not appear to be reflected in the bone responses as measured by GAG content in PISF.
Assuntos
Perda do Osso Alveolar/metabolismo , Implantes Dentários , Planejamento de Prótese Dentária , Análise do Estresse Dentário , Líquido do Sulco Gengival/metabolismo , Glicosaminoglicanos/metabolismo , Idoso , Perda do Osso Alveolar/etiologia , Fenômenos Biomecânicos , Sulfatos de Condroitina/análise , Sulfatos de Condroitina/metabolismo , Prótese Parcial Fixa/efeitos adversos , Prótese Parcial Removível/efeitos adversos , Feminino , Líquido do Sulco Gengival/química , Glicosaminoglicanos/análise , Humanos , Ácido Hialurônico/análise , Ácido Hialurônico/metabolismo , Masculino , Pessoa de Meia-Idade , Estresse MecânicoRESUMO
Glycosaminoglycans (GAG) present in peri-implant sulcus fluid (PISF) were used as an indicator of the metabolic activity in the supporting tissues of implants placed in maxillary bone or maxillary bone and bone grafts together. The study included 16 patients who received implants (Brånemark system(R)) and sinus-inlay bone grafts. In 12 of these patients, the implants were placed in either maxillary bone alone or maxillary bone and sinus-inlay bone grafts in combination. Altogether the patients received a total of 102 implants, of which 73 implants were placed in bone grafts and 29 implants in maxillary bone alone. Samples of PISF were tested at 2-8 days and at 6 months after abutment connection. Levels of the GAG's chondroitin-4-sulphate (C4S) and hyaluronan (HA) were assessed using cellulose acetate electrophoresis and densitometric scanning of Alcian blue-stained strips against known GAG standards. The C4S was used as a bone metabolic marker, and HA was used to reflect the progress of soft tissue healing. Comparing grafted and non-grafted regions, there was no significant difference in either C4S levels or HA levels during the first 8 days or at the 6 months period. The levels of HA from the first week collection did not differ significantly from the HA level after 6 months in either type of bone. However, the level of C4S was significantly lower after 6 months than during the first week, in both maxillary and grafted bone but consistent with a normal metabolic turnover. C4S can therefore be used as an indicator of the progressive healing of bone adjacent to implants.
Assuntos
Transplante Ósseo , Implantes Dentários , Líquido do Sulco Gengival/química , Glicosaminoglicanos/análise , Maxila/cirurgia , Seio Maxilar/cirurgia , Adulto , Idoso , Azul Alciano , Sulfatos de Condroitina/análise , Corantes , Densitometria , Implantação Dentária Endóssea , Dermatan Sulfato/análise , Feminino , Seguimentos , Heparitina Sulfato/análise , Humanos , Ácido Hialurônico/análise , Arcada Edêntula/metabolismo , Arcada Edêntula/cirurgia , Masculino , Maxila/metabolismo , Seio Maxilar/metabolismo , Pessoa de Meia-Idade , Estatística como Assunto , Estatísticas não Paramétricas , CicatrizaçãoRESUMO
PURPOSE: The aim of this prospective study was to determine whether a machine-fabricated titanium fixed partial denture veneered with a low-temperature fused porcelain is an acceptable treatment modality. MATERIALS AND METHODS: The study originally included 25 patients with 37 fixed partial dentures of three to seven units, with a total of 151 units including 98 abutments. A clinical examination using the California Dental Association quality evaluation system and radiologic examination and registration of complications was conducted at the time of insertion and after 1 and 2 years. RESULTS: After 2 years, 123 units (including 80 abutments) remained for examination. Twenty-eight units (including 18 abutments) were lost during the follow-up period. The losses were because of drop-out (eight cases), root fracture (two cases), caries (six cases), and periodontitis (two cases). One fixed partial denture fractured after 18 months and was therefore remade. In all, porcelain fractures occurred in two patients, both with severe parafunctional habits. At baseline, the California Dental Association rating system for marginal integrity was "excellent" for 72 abutments and "acceptable" for 26 abutments. At the 2-year follow-up the corresponding rating was "excellent" for 46 abutments, "acceptable" for 30 abutments, and "not acceptable" for four abutments. The latter marginal defects were corrected with restorations. For surface and color the corresponding ratings were "excellent" for 137 units and "acceptable" for 14 units at baseline, and "excellent" for 80 units and "acceptable" for 43 units at the 2-year follow-up. Bleeding index increased from 24% at baseline to 33% after 2 years. CONCLUSION: The study confirms that for an observation period of 2 years, fixed partial dentures made by the Procera method seem to be an acceptable treatment modality. They are a suitable alternative to fixed partial dentures with porcelain fused to high-noble alloys.
Assuntos
Porcelana Dentária , Planejamento de Dentadura , Prótese Parcial Fixa , Ligas Metalo-Cerâmicas , Titânio , Adulto , Idoso , Idoso de 80 Anos ou mais , Dente Suporte , Falha de Restauração Dentária , Feminino , Seguimentos , Humanos , Masculino , Teste de Materiais , Pessoa de Meia-Idade , Estudos Prospectivos , Estresse Mecânico , Resultado do TratamentoRESUMO
In order to satisfy the need to restore the aesthetics, phonetics and comfort and to facilitate optimal hygiene procedures, 20 edentulous patients were treated with a new concept of overdenture therapy on implants and modum Brånemark. After 24 +/- 3.5 months the patients were re-examined. They were asked to answer a questionnaire and use a Visual Analogue Scale (VAS) to give their opinion on the prosthetic treatment. The results indicate that an implant-retained overdenture in the maxilla with this design can satisfy the patients needs in aesthetics, phonetics and comfort and can facilitate oral hygiene measures.
Assuntos
Implantes Dentários , Planejamento de Prótese Dentária , Revestimento de Dentadura , Idoso , Idoso de 80 Anos ou mais , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/patologia , Processo Alveolar/diagnóstico por imagem , Índice de Placa Dentária , Feminino , Seguimentos , Humanos , Masculino , Maxila , Pessoa de Meia-Idade , Satisfação do Paciente , Falha de Prótese , Radiografia , Inquéritos e QuestionáriosRESUMO
In a combined in vitro and in vivo study strain gauges were used to register the deformation in two terminal implant abutment cylinders, when connecting three different prosthetic appliances. The prosthetic constructions were placed on the abutments and fastened in vitro and in vivo by using different torque sequences. Furthermore, in the in vitro situation the three medial abutments were replaced by abutments which were 100 microns shorter. The results show that even if the prosthetic constructions were judged to have a good clinical fit, relatively large External Preloads were registered both in vitro and in vivo. No significant differences in axial force or in bending movement were found between the torque sequences in vivo. There were, however, significant differences in axial force as well as in bending moment in the in vitro experiment. When the shorter medial abutments were used in vitro, a change in the axial force of approximately 200 N was registered. The results confirm that the methodological approach used in this study is valid when evaluating preloads.
Assuntos
Dente Suporte , Implantes Dentários , Retenção em Prótese Dentária/instrumentação , Prótese Dentária Fixada por Implante , Análise do Estresse Dentário , Análise de Variância , Planejamento de Prótese Dentária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Maleabilidade , Ajuste de Prótese , Valores de Referência , Reprodutibilidade dos Testes , TorqueRESUMO
Retinoic acid induces cell differentiation and suppresses cell growth in a wide spectrum of cell lines, and down-regulation of activator protein-1 activity by retinoic acid contributes to these effects. In embryonic stem cell-like F9 teratocarcinoma cells, which are widely used to study retinoic acid actions on gene regulation and early embryonic differentiation, retinoic acid treatment for 4 days resulted in suppression of cell growth and differentiation into primitive and then visceral endoderm-like cells, accompanied by a suppression of serum-induced c-Fos expression. The MAPK (ERK) pathway was involved in mitogenic signaling in F9 cells stimulated with serum. Surprisingly, although c-Fos expression was reduced, the MAPK activity was not decreased by retinoic acid treatment. We found that retinoic acid treatment inhibited the phosphorylation of Elk-1, a target of activated MAPK required for c-Fos transcription. In F9 cells, the MAPK/MEK inhibitor PD98059 suppressed Elk-1 phosphorylation and c-Fos expression, indicating that MAPK activity is required for Elk-1 phosphorylation/activation. Phosphoprotein phosphatase 2B (calcineurin), the major phosphatase for activated Elk-1, is not the target in the disassociation of MAPK activation and c-Fos expression since its inhibition by cyclosporin A or activation by ionomycin had no significant effects on serum-stimulated c-Fos expression and Elk-1 phosphorylation. Thus, we conclude that retinoic acid treatment to induce F9 cell differentiation uncouples Ras/MAPK activation from c-Fos expression by reduction of Elk-1 phosphorylation through a mechanism not involving the activation of phosphoprotein phosphatase 2B.
Assuntos
Carcinoma Embrionário/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proteínas de Ligação a DNA , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Fatores de Transcrição , Tretinoína/farmacologia , Animais , Calcineurina/metabolismo , Carcinoma Embrionário/enzimologia , Carcinoma Embrionário/patologia , Ativação Enzimática , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Camundongos , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Fosforilação , Proteínas Proto-Oncogênicas/metabolismo , Células Tumorais Cultivadas , Proteínas Elk-1 do Domínio etsRESUMO
F9 embryonic stem cell-like teratocarcinoma cells are widely used to study early embryonic development and cell differentiation. The cells can be induced by retinoic acid to undergo endodermal differentiation. The retinoic acid-induced differentiation accompanies cell growth suppression, and thus, F9 cells are also often used as a model for analysis of retinoic acid biological activity. We have recently shown that MAPK activation and c-Fos expression are uncoupled in F9 cells upon retinoic acid-induced endodermal differentiation. The expression of the candidate tumor suppressor Disabled-2 is induced and correlates with cell growth suppression in F9 cells. We were not able to establish stable Disabled-2 expression by cDNA transfection in F9 cells without induction of spontaneous cell differentiation. Transient transfection of Dab2 by adenoviral vector nevertheless suppresses Elk-1 phosphorylation, c-Fos expression, and cell growth. In PA-1, another teratocarcinoma cell line of human origin that has no or very low levels of Disabled-2, retinoic acid fails to induce Disabled-2, correlating with a lack of growth suppression, although PA-1 is responsive to retinoic acid in morphological change. Transfection and expression of Disabled-2 in PA-1 cells mimic the effects of retinoic acid on growth suppression; the Disabled-2-expressing cells reach a much lower saturation density, and serum-stimulated c-Fos expression is greatly suppressed and disassociated from MAPK activation. Thus, Dab2 is one of the principal genes induced by retinoic acid involved in cell growth suppression, and expression of Dab2 alone is sufficient for uncoupling of MAPK activation and c-Fos expression. Resistance to retinoic acid regulation in PA-1 cells likely results from defects in retinoic acid up-regulation of Dab2 expression.