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1.
Neuroradiology ; 66(6): 907-917, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38607437

RESUMO

PURPOSE: This study aimed to compare the radiological tumor (T)-category using multiparametric MRI with the pathological T category in patients with oral tongue squamous cell carcinoma (OTSCC) and to examine which is a better predictor of prognosis. METHODS: This retrospective study included 110 consecutive patients with surgically resected primary OTSCC who underwent preoperative contrast-enhanced MRI. T categories determined by maximum diameter and depth of invasion were retrospectively assessed based on the pathological specimen and multiparametric MRI. The MRI assessment included the axial and coronal T1-weighted image (T1WI), axial T2-weighted image (T2WI), coronal fat-suppressed T2WI, and axial and coronal fat-suppressed contrast-enhanced T1WI (CET1WI). Axial and coronal CET1WI measurements were divided into two groups: measurements excluding peritumoral enhancement (MEP) and measurements including peritumoral enhancement. The prognostic values for recurrence and disease-specific survival after radiological and pathological T categorization of cases into T1/T2 and T3/T4 groups were compared. RESULTS: The T category of MEP on coronal CET1WI was the most relevant prognostic factor for recurrence [hazard ratio (HR) = 3.30, p = 0.001] and the HR was higher than the HR for pathological assessment (HR = 2.26, p = 0.026). The T category determined by MEP on coronal CET1WI was also the most relevant prognostic factor for disease-specific survival (HR = 3.12, p = 0.03), and the HR was higher than the HR for pathological assessment (HR = 2.02, p = 0.20). CONCLUSION: The T category determined by MEP on the coronal CET1WI was the best prognostic factor among all radiological and pathological T category measurements.


Assuntos
Carcinoma de Células Escamosas , Meios de Contraste , Imageamento por Ressonância Magnética , Neoplasias da Língua , Humanos , Neoplasias da Língua/diagnóstico por imagem , Neoplasias da Língua/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Idoso , Imageamento por Ressonância Magnética/métodos , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Adulto , Estadiamento de Neoplasias , Idoso de 80 Anos ou mais , Recidiva Local de Neoplasia/diagnóstico por imagem , Taxa de Sobrevida , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Invasividade Neoplásica
2.
Int J Clin Pract ; 75(11): e14785, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34480837

RESUMO

BACKGROUND: Implementation of antimicrobial stewardship programmes improve antimicrobial therapies and thus result in better patient outcomes and safety. The impact of prospective audit and feedback (PAF) is likely dependent on how frequently it is conducted, and how quickly after antibiotic prescription it is initiated. To our knowledge, however, no report has yet investigated the impact of an increase in monitoring frequency per day on PAF strategy. Here, we evaluated the clinical impact of an increase in monitoring frequency per day as a PAF strategy in patients receiving antimicrobial injections. METHODS: We conducted a single-centre, retrospective observational pre-post study to evaluate the impact of increasing the frequency of monitoring from once daily (once daily review group) to twice daily (twice daily review group). Time to intervention and clinical outcomes were compared before and after implementation of twice daily review. RESULTS: Time to intervention for inappropriate antimicrobial therapy was significantly shorter in the twice daily review group than the once daily review group (5.1 ± 6.1 hours vs 29.9 ± 21.5 hours, HR: 4.53, 95% CI: 2.90-7.07, P < .001). The twice daily review group had a significantly lower rate of clinical failure (16.2% vs 38.3%, P = .004) and hepatotoxicity (4.1% vs 15.0%, P = .035) than the once daily review group. CONCLUSIONS: An increase in monitoring frequency from once daily to twice daily significantly shortened the time to intervention for inappropriate antimicrobial therapy, with a concomitant reduction in clinical failure and hepatotoxicity.


Assuntos
Anti-Infecciosos , Gestão de Antimicrobianos , Antibacterianos/uso terapêutico , Retroalimentação , Humanos , Estudos Prospectivos , Estudos Retrospectivos
3.
J Bone Miner Metab ; 37(3): 467-474, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30187276

RESUMO

The central nervous system in adult mammals does not heal spontaneously after spinal cord injury (SCI). However, SCI treatment has been improved recently following the development of cell transplantation therapy. We recently reported that fibroblast growth factor (FGF) 2-pretreated human dental pulp cells (hDPCs) can improve recovery in a rat model of SCI. This study aimed to investigate mechanisms underlying the curative effect of SCI enhanced via FGF2 pretreatment; we selected three hDPC lines upon screening for the presence of mesenchymal stem cell markers and of their functionality in a rat model of SCI, as assessed using the Basso, Beattie, and Bresnahan score of locomotor functional scale, electrophysiological tests, and morphological analyses. We identified FGF2-responsive genes via gene expression analyses in these lines. FGF2 treatment upregulated GABRB1, MMP1, and DRD2, which suggested to contribute to SCI or central the nervous system. In an expanded screening of additional lines, GABRB1 displayed rather unique and interesting behavior; two lines with the lowest sensitivity of GABRB1 to FGF2 treatment displayed an extremely minor effect in the SCI model. These findings provide insights into the role of FGF2-responsive genes, especially GABRB1, in recovery from SCI, using hDPCs treated with FGF2.


Assuntos
Polpa Dentária/citologia , Fator 2 de Crescimento de Fibroblastos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/terapia , Animais , Modelos Animais de Doenças , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Humanos , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/fisiopatologia
4.
Int J Clin Pract ; 73(1): e13262, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30259617

RESUMO

BACKGROUND: Antimicrobial stewardship is required to ensure the appropriate use of antimicrobials. However, few reports have shown the impact of antimicrobial stewardship on clinical outcomes. METHODS: To evaluate the clinical outcomes of implementing a prospective audit with intervention and feedback without carbapenem pre-authorisation, we conducted a single-centre, prospective cohort study in patients who received carbapenem injection. Subjects were allocated to groups receiving antimicrobial agents before (non-intervention group) or after (intervention group) the implementation of an antimicrobial stewardship programme in the clinical setting. RESULTS: The intervention facilitated the rate of choice of effective antimicrobials on day 2 from the onset of infection (from 63.2% to 90.2%; P < 0.001). Moreover, the rates of clinical failure-free survival (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.47-0.89; P = 0.008) and re-infection-free survival (HR, 0.35; 95% CI, 0.18-0.68; P = 0.002) were significantly higher in the intervention group than in the non-intervention group. A multivariate Cox proportional hazard analysis indicated that non-implementation of antimicrobial stewardship was a significant risk factor for clinical failure in patients receiving carbapenem injection (HR, 1.56; 95% CI, 1.11-2.19; P = 0.010). CONCLUSIONS: Our prospective audit with intervention and feedback strategy without carbapenem restriction facilitated the choice of optimal antimicrobials at an early stage of infection and improved clinical outcomes in patients who received carbapenem.


Assuntos
Antibacterianos/uso terapêutico , Gestão de Antimicrobianos/métodos , Infecções Bacterianas/tratamento farmacológico , Carbapenêmicos/uso terapêutico , Idoso , Intervalo Livre de Doença , Retroalimentação , Feminino , Humanos , Injeções , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Prospectivos
5.
Int J Clin Pract ; 73(5): e13332, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30810264

RESUMO

BACKGROUND: Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has the potential to permit early organism identification and optimization of antibiotic therapy. However, MALDI-TOF MS combined with antimicrobial stewardship is available at only a limited number of institutions. Here, we evaluated the clinical impact of implementing MALDI-TOF MS combined with antimicrobial stewardship intervention in patients with bloodstream infections. METHODS: We conducted a single-centre, prospective cohort study to evaluate the clinical impact of implementing MALDI-TOF MS combined with antimicrobial stewardship intervention in patients with bloodstream infections. Processes and clinical outcomes in patients with bloodstream infections were compared before and after implementation of MALDI-TOF MS. RESULTS: Compared with the conventional identification method, MALDI-TOF MS combined with antimicrobial stewardship intervention significantly decreased the time to organism identification (48.6 ± 46.0 hours vs 78.1 ± 38.9 hours, P < 0.001), effective antimicrobial therapy (12.9 ± 19.0 hours vs 26.2 ± 44.8 hours, P < 0.001) and optimal antimicrobial therapy (53.3 ± 55.0 hours vs 91.7 ± 88.7 hours, P < 0.001. Moreover, the rate of clinical failure (14.0% vs 33.3%, P < 0.001) and incidence of adverse events (7.5% vs 23.9%, P < 0.001) was lower in the MALDI-TOF MS group than in the conventional identification group. A multivariate Cox proportional hazard analysis indicated that implementation of MALDI-TOF MS was a protective factor against clinical failure in patients with bloodstream infections (hazard ratio, 0.61; 95% confidence interval, 0.38-0.99; P = 0.047). CONCLUSIONS: Implementation of the MALDI-TOF MS combined with antimicrobial stewardship intervention facilitated early optimization of antimicrobial therapy with a remarkable concomitant reduction in clinical failure and adverse events in patients with bloodstream infections.


Assuntos
Gestão de Antimicrobianos/métodos , Bacteriemia/tratamento farmacológico , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Idoso , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Bacteriemia/diagnóstico , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Centros de Atenção Terciária , Fatores de Tempo
6.
J Clin Pharm Ther ; 44(3): 454-462, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30723924

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Implementation of an antifungal stewardship programme is a recognized need. However, there is insufficient information to confirm the impact of antifungal stewardship interventions. Further, few studies have evaluated the clinical effects of an antifungal stewardship intervention using 1-3, ß-D-glucan (ßDG) testing. The aim of the present study was to evaluate the impact of implementing an antifungal stewardship with monitoring of ßDG values on antifungal use and clinical outcomes. METHODS: A single institutional prospective cohort study was conducted to evaluate the impact of implementing daily reviews of antifungal agents and monitoring patients who measured ßDG values since August 2013. Antifungal consumption and clinical outcomes in patients with Candida bloodstream infection were compared before and after the intervention. RESULTS: After implementation of the programme, parental antifungal use was significantly reduced compared to that before intervention (P = 0.006). In the after-intervention group, the rate of 60-day clinical failure in patients with Candida bloodstream infection was significantly reduced, from 80.0% (28/35) to 36.4% (8/22) (P < 0.001), and the rate of 60-day mortality associated with Candida bloodstream infection tended to be reduced, from 42.9% (15/35) to 18.2% (4/22) (P = 0.081) compared to the before-intervention group. The incidence of adverse events associated with antifungal agents was significantly lower in the after-intervention group than in the before-intervention group (51.4% [18/35] vs 13.6% [3/22], P = 0.004). WHAT IS NEW AND CONCLUSION: Our findings suggest that daily review of the use of antifungal agents and monitoring of measured ßDG values was highly effective in reducing antifungal consumption and improving the clinical outcomes of patients with Candida bloodstream infection.


Assuntos
Antifúngicos/administração & dosagem , Candidíase/tratamento farmacológico , Glucanos/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Candida/efeitos dos fármacos , Candidíase/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
7.
Int J Clin Pract ; : e13293, 2018 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-30414352

RESUMO

BACKGROUND: The standard duration of administration of antimicrobial prophylaxis in surgery and non-surgical invasive therapy was shortened according to the promotion of appropriate use. Here, we conducted an intervention to optimise antimicrobial prophylaxis by revising all relevant clinical pathways based on the most recent guidelines. METHODS: We conducted a single-centre, prospective cohort study in patients who received antimicrobial prophylaxis to evaluate outcomes following revision of the clinical pathways for antimicrobial prophylaxis. Antibiotic consumption and the duration of antibiotic administration were compared before and after revising the clinical pathways. RESULTS: Thirty-five of 171 clinical pathways were considered inappropriate for antimicrobial use and were optimised. After this revision, the duration of antibiotic administration was significantly shortened (before revision: 3 [1-5] days vs after revision: 2 [1-3] days, median [interquartile range], P < 0.001). The rate of discontinuation of antibiotics within 48 h after surgery or non-surgical invasive therapy was significantly higher after the revision (62.4% vs 81.8%, P < 0.001). In contrast, the incidence of surgical site infection (SSI) was not significantly different before and after the revision (5.7% vs 4.3%, P = 0.177). A multivariate Cox proportional analysis indicated that revision of the clinical pathways was one of the prognostic factors associated with the discontinuation of antibiotics within 48 h after surgery or non-surgical invasive therapy (hazard ratio, 0.69; 95% confidence interval, 0.63-0.76, P < 0.001). CONCLUSIONS: Our findings suggest that revising all relevant clinical pathways was highly effective in reducing antibiotic consumption and shortening the antibiotic administration period without increasing the incidence of SSIs.

8.
J Oral Pathol Med ; 39(5): 407-19, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20202092

RESUMO

BACKGROUND: Recently, oral sensory complaints (OSC) were proposed as a disease entity to represent idiopathic sensory disturbances of dry mouth, burning mouth, and taste disturbance, even though neither the status of OSC in the general population nor its underlying mechanism has yet been elucidated. Moreover, these three OSC-related complaints have not been assessed in combination by means of a visual analog scale (VAS) in a large-scale, community-dwelling population of a broad age range. METHODS: In a 1188-member community-dwelling adult population, comprised of 373 males and 815 females, aged 20-90 years, the three OSC-related complaints and stimulated salivary flow rate (SSFR) were assessed by means of a VAS and modified Saxon test, respectively. Association of each complaint with age, gender, SSFR, and other complaints was analyzed. RESULTS: Increases in both prevalence and intensity of subjective dry mouth and burning mouth were associated closely with decreasing SSFR. Even for taste disturbance, which may be affected less significantly by salivation status than the other two complaints, a significant association was suggested between decreasing SSFR and especially severe taste disturbance. However, these oral complaints were found in considerable prevalence even in the individuals with high SSFR. Often overlapping presentation of these complaints and a close association in intensity between the complaints to each other were also found. CONCLUSIONS: Hyposalivation may be a significant and common etiology for the three oral complaints, although the considerable prevalence of complaints without hyposalivation suggests other etiologies, including those related to the OSC.


Assuntos
Síndrome da Ardência Bucal/etiologia , Saliva/metabolismo , Distúrbios do Paladar/etiologia , Xerostomia/etiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Distribuição de Qui-Quadrado , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estimulação Física , Análise de Regressão , Taxa Secretória , Fatores Sexuais , Inquéritos e Questionários , Xerostomia/complicações , Adulto Jovem
9.
Oncol Rep ; 22(3): 501-7, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19639195

RESUMO

To assess the effect of neoadjuvant therapy using tegafur/uracil (UFT) and radiation therapy on the 5-fluorouracil (5-FU) metabolic and relative enzymes, thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT) and thymidine phosphorylase (TP) in oral squamous cell carcinoma (OSCC), we examined the mRNA expression and immunohistochemical staining status of these enzymes using 17 surgical specimens. Seven patients did not receive any neoadjuvant therapy and 10 were treated with UFT and local irradiation therapy. Our result showed that the mRNA expression of these enzymes in neoadjuvant group was not significantly different from that of non-treated group using real-time quantitative PCR. To confirm the protein expression, we also carried out immunohistological staining of TS and DPD two key enzymes in the 5-FU metabolism, using the same specimens. Immunohistological staining status did not correspond to the results of mRNA analysis completely, though no significant difference between the groups was observed. Furthermore, no significant relationship between the UFT administration period and mRNA expression of the 5-FU metabolic enzymes was observed in neoadjuvant therapy group and also the distribution of the enzyme mRNA expression levels was similar to that of non-treated group. The results suggested that the neoadjuvant therapy of OSCC might not affect the expression status of 5-FU metabolic and relative enzymes in surgical tumor samples and the tumor tissues might serve as a useful specimen source to analyze the expression status of the 5-FU metabolic and relative enzymes and to determine the prospective efficiency of 5-FU-based adjuvant chemotherapy.


Assuntos
Antimetabólitos Antineoplásicos/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Fluoruracila/metabolismo , Neoplasias Bucais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Di-Hidrouracila Desidrogenase (NADP)/análise , Di-Hidrouracila Desidrogenase (NADP)/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Orotato Fosforribosiltransferase/análise , Orotato Fosforribosiltransferase/genética , Tegafur/administração & dosagem , Timidina Fosforilase/análise , Timidina Fosforilase/genética , Timidilato Sintase/análise , Timidilato Sintase/genética , Uracila/administração & dosagem
10.
Dentomaxillofac Radiol ; 47(6): 20180085, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29595323

RESUMO

OBJECTIVES: The current study aimed to assess CT and MRI characteristics of histological subtypes of head and neck ossifying fibroma (OF). METHODS: 12 patients with histopathologically-proven head and neck OF were included in this study. Lesions were pathologically classified into three histological subtypes: eight cement-OFs (COFs), three juvenile psammomatoid OFs (JPOFs), and one juvenile trabecular OF (JTOF). All patients underwent CT examination, while seven also underwent MRI. Imaging characteristics were retrospectively assessed. RESULTS: On CT images, the lesion margins were well-defined in nine patients (75%) (seven COFs and two JPOFs), partially ill-defined in two (17%) (one COF and one JTOF), and ill-defined in one (8%) (one JPOF). The continuity of the eroded overlying bone cortex was maintained in nine patients (75%) (seven COFs and two JPOFs) but disrupted in three (25%) (one COF, one JPOF, one JTOF). With respect to lesion density, homogeneous ground-glass opacity was observed in five patients (42%) (five COFs), target-like appearance in three (25%) (two COFs, one JPOF), and mixture of hyper- and hypodense areas were observed in four (33%) (one COF, two JPOFs, one JTOF). MR signal intensity was homogeneous in two patients (29%) (two COFs) and heterogeneous in five (71%) (two COFs, two JPOFs, one JTOF). CONCLUSIONS: COFs tended to exhibit well-defined margins and preserved continuity of the overlying bone cortex. COFs were usually homogeneous, whereas JPOFs and JTOF were always heterogeneous. Target-like appearance was one of the characteristics of OFs, but it was observed in both COF and JPOF.


Assuntos
Neoplasias Ósseas , Fibroma Ossificante , Adolescente , Adulto , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Criança , Feminino , Fibroma Ossificante/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
11.
Oncol Rep ; 17(4): 879-85, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17342331

RESUMO

The preventive effects of the dietary administration of brown rice and rice bran fermented with Aspergillus oryzae (FBRA) on oral carcinogenesis induced by 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. At 7 weeks of age, the animals were given 20 ppm 4-NQO in their drinking water for 8 weeks to induce tongue neoplasms. Groups of rats were fed diets containing 5 or 10% FBRA during the initiation or postinitiation phases of the 4-NQO-induced oral carcinogenesis. The other groups consisted of rats fed 10% FBRA or untreated rats. At the termination of the study (week 32), the incidences, multiplicities of tongue lesions (pre-neoplasms and neoplasms) and the cell proliferation activity estimated by the 5-bromodeoxyuridine (BrdU)-labeling index were compared among the groups. Feeding of 5% FBRA during the initiation phase significantly decreased the incidence (68.2 vs 36.8%; p<0.05) and multiplicity (1.05+/-0.84 vs 0.37+/-0.50; p<0.005) of the tongue carcinoma. When feeding of 10% FBRA occurred after the 4-NQO exposure, the multiplicity of tongue carcinoma was also reduced (1.05+/-0.84 vs 0.52+/-0.60; p<0.05). In addition, the dietary administration of FBRA at both doses significantly decreased the BrdU-labeling index in the oral squamous epithelium (p<0.05). Although a dose-dependent response was not observed, FBRA is effective in suppressing the development of 4-NQO-induced oral carcinogenesis by its concurrent exposure to the carcinogen. The inhibitory effect could be related to the suppression of the hyperproliferation of cells in the tongue epithelium and the radical scavenging activity of FBRA.


Assuntos
Transformação Celular Neoplásica , Fibras na Dieta/uso terapêutico , Neoplasias Bucais/prevenção & controle , Oryza , Lesões Pré-Cancerosas/prevenção & controle , Animais , Bromodesoxiuridina/análise , Bromodesoxiuridina/metabolismo , Transformação Celular Neoplásica/induzido quimicamente , Óxidos N-Cíclicos/toxicidade , Fibras na Dieta/administração & dosagem , Masculino , Neoplasias Bucais/induzido quimicamente , Lesões Pré-Cancerosas/induzido quimicamente , Ratos , Ratos Endogâmicos F344
13.
Oncol Rep ; 15(4): 869-74, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16525673

RESUMO

To investigate the effects of fermented brown rice (FBRA) on the development of hereditary hepatitis in Long-Evans Cinnamon (LEC) rats, we compared the incidence and grades of acute hepatitis among rats fed 5% and 10% FBRA in the conventional diet and the conventional diet alone. Both the 5% and 10% FBRA-supplemented diets indicated a tendency to prevent the development of hepatitis, and the significant effect of 10% FBRA was observed until 16-17 weeks of age in the accumulated incidence and survival ratio compared with the unsupplemented conventional diet, although no significant difference was observed between 5% and 10% FBRA-supplemented diets. At the age of 12 weeks, which is just before the rats develop hepatitis, serum copper levels in rats fed either of the test diets were similar to those in rats fed the conventional diet. Furthermore, the copper concentration in liver tissue at 12 weeks of age was not changed by the test diet. These results suggest that FBRA has preventive effects on the development of hepatitis in LEC rats and may play an important role in protecting the liver against the free radicals induced by copper accumulation in the liver.


Assuntos
Hepatite/prevenção & controle , Oryza , Preparações de Plantas/farmacologia , Doença Aguda , Animais , Peso Corporal/efeitos dos fármacos , Dieta , Relação Dose-Resposta a Droga , Feminino , Fermentação , Hepatite/sangue , Hepatite/mortalidade , Preparações de Plantas/administração & dosagem , Ratos , Ratos Endogâmicos LEC , Taxa de Sobrevida , Fatores de Tempo
14.
Biochim Biophys Acta ; 1589(1): 15-30, 2002 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-11909638

RESUMO

We investigated whether transforming growth factor-beta (TGF-beta) stimulates the induction of heat shock protein (HSP) 27 and HSP70 in osteoblast-like MC3T3-E1 cells and the mechanism underlying the induction. TGF-beta increased the level of HSP27 but had no effect on the HSP70 level. TGF-beta stimulated the accumulation of HSP27 dose-dependently, and induced an increase in the level of mRNA for HSP27. TGF-beta induced the phosphorylation of p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase. The HSP27 accumulation induced by TGF-beta was significantly suppressed by PD98059, an inhibitor of the upstream kinase of p44/p42 MAP kinase, or SB203580, an inhibitor of p38 MAP kinase. PD98059 and SB203580 suppressed the TGF-beta-stimulated increase in the level of mRNA for HSP27. Retinoic acid, a vitamin A (retinol) metabolite, which alone had little effect on the HSP27 level, markedly enhanced the HSP27 accumulation stimulated by TGF-beta. Retinoic acid enhanced the TGF-beta-induced increase of mRNA for HSP27. The amplification of TGF-beta-stimulated HSP27 accumulation by retinoic acid was reduced by PD98059 or SB203580. Retinoic acid failed to affect the TGF-beta-induced phosphorylation of p44/p42 MAP kinase or p38 MAP kinase. These results strongly suggest that p44/p42 MAP kinase and p38 MAP kinase take part in the pathways of the TGF-beta-stimulated HSP27 induction in osteoblasts, and that retinoic acid upregulates the TGF-beta-stimulated HSP27 induction at a point downstream from p44/p42 MAP kinase and p38 MAP kinase.


Assuntos
Proteínas de Choque Térmico/biossíntese , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Osteoblastos/efeitos dos fármacos , Tretinoína/farmacologia , Animais , Northern Blotting , Linhagem Celular , Ativação Enzimática , Flavonoides/farmacologia , Proteínas de Choque Térmico/genética , Imidazóis/farmacologia , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno , Osteoblastos/metabolismo , Fosforilação/efeitos dos fármacos , Piridinas/farmacologia , RNA Mensageiro/análise , Transdução de Sinais , Fator de Crescimento Transformador beta/farmacologia , Regulação para Cima , Proteínas Quinases p38 Ativadas por Mitógeno
15.
Cancer Genet Cytogenet ; 159(2): 99-104, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15899380

RESUMO

In order to characterize the chromosomal alterations in ameloblastomas, a combination of comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) techniques was performed on 9 tumors. Chromosomal alterations including a gain at 1q and losses at 1pter, 10q, and 22q could be detected by CGH only in 1 tumor. Interphase FISH analysis, using centromeric probes for chromosomes 1, 10, and 22 as well as region-specific probes for 1p36 and 10q26, revealed the most frequent alterations to exist in the tumor with the abnormal CGH profile. These alterations included marked to slight increases of monosomic cells for chromosome 10 (91.5%), 10q26 (35.8%), 1p36 (24.4%), and chromosome 22 (18.8%), as well as significant elevations of trisomic cells for chromosome 1 (41.2%). Moreover, FISH analysis revealed a frequent loss of chromosome 22 in all tumors examined, except for one lesion, indicating that loss of the entire or a part of this chromosome is a common event in ameloblastomas, possibly being a predisposing factor to ameloblastoma tumorigenesis.


Assuntos
Aberrações Cromossômicas , Adolescente , Adulto , Idoso , Ameloblastoma , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 10 , Cromossomos Humanos Par 22 , Feminino , Dosagem de Genes , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Hibridização de Ácido Nucleico
16.
Cell Signal ; 14(12): 999-1004, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12359305

RESUMO

We previously reported that extracellular sphingomyelinase induces sphingomyelin hydrolysis in osteoblast-like MC3T3-E1 cells and that mitogen-activated protein (MAP) kinases are involved in bone morphogenetic protein (BMP)-4-stimulated osteocalcin synthesis in these cells. In the present study, we investigated whether sphingomyelinase affects BMP-4-stimulated synthesis of osteocalcin in osteoblast-like MC3T3-E1 cells. Sphingomyelinase significantly enhanced the BMP-4-stimulated osteocalcin synthesis. Among sphingomyelin metabolites, C(2)-ceramide enhanced the BMP-4-stimulated osteocalcin synthesis while sphingosine and sphingosine 1-phosphate had little effect on the synthesis. D-erythro-MAPP, an inhibitor of ceramidase, amplified the sphingomyelinase-effect on the osteocalcin synthesis. C(2)-ceramide suppressed the BMP-4-induced phosphorylation of p44/p42 MAP kinase, while having little effect on the phosphorylation of Smad1 and p38 MAP kinase. Taken together, our results strongly suggest that extracellular sphingomyelinase enhances the BMP-stimulated osteocalcin synthesis via ceramide in osteoblasts and that the effect of ceramide is exerted at a point upstream from p44/p42 MAP kinase.


Assuntos
Proteínas Morfogenéticas Ósseas/farmacologia , Ceramidas/fisiologia , Lisofosfolipídeos , Osteoblastos/metabolismo , Osteocalcina/biossíntese , Esfingomielina Fosfodiesterase/farmacologia , Esfingosina/análogos & derivados , Amidoidrolases/antagonistas & inibidores , Animais , Proteína Morfogenética Óssea 4 , Linhagem Celular , Ceramidases , Proteínas de Ligação a DNA/metabolismo , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Inibidores Enzimáticos/farmacologia , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Miristatos/farmacologia , Osteoblastos/efeitos dos fármacos , Fosforilação , Propanolaminas/farmacologia , Proteínas Smad , Proteína Smad1 , Esfingosina/farmacologia , Transativadores/metabolismo
17.
Eur J Pharmacol ; 466(3): 245-53, 2003 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-12694807

RESUMO

We investigated whether tumor necrosis factor-alpha (TNF-alpha) stimulates the induction of heat shock protein 27 (HSP27) in human neutrophils and the mechanism underlying this induction. In intact neutrophils, almost no HSP27 was detected. Stimulation of neutrophils by TNF-alpha increased the levels of HSP27 in the presence, but not in the absence, of cycloheximide. Reverse transcription-polymerase chain reaction (RT-PCR) experiments showed that TNF-alpha also induced HSP27 mRNA in the presence of cycloheximide. TNF-alpha induced the phosphorylation of p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase. The HSP27 accumulation induced by TNF-alpha was significantly suppressed by 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole (SB203580) or 4-(4-fluorophenyl)-2-(4-nitrophenyl)-5-(4-pyridyl)-1H-imidazole (PD169316); both are specific inhibitors of p38 MAP kinase, but not by 2'-amino-3'-methoxyflavone (PD098059, a specific inhibitor of the upstream kinase that activates p44/p42 MAP kinase). The accumulation of HSP27 induced by TNF-alpha plus cycloheximide was also suppressed by pretreatment with a specific protein kinase C (PKC) inhibitor. Furthermore, phorbol myristate acetate (PMA), a PKC stimulant, but not dibutyryl cyclic AMP, a protein kinase A stimulant, stimulated the accumulation of HSP27. Interestingly, SB203580 did not inhibit PMA-stimulated HSP27 induction. These results strongly suggest that TNF-alpha may act as the regulator of HSP27 induction in neutrophils. p38 MAP kinase (but not p44/p42 MAP kinase) and PKC take part in TNF-alpha-stimulated HSP27 induction in human neutrophils.


Assuntos
Proteínas de Choque Térmico/biossíntese , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neutrófilos/metabolismo , Apoptose/efeitos dos fármacos , Proteínas Quinases Dependentes de Cálcio-Calmodulina/antagonistas & inibidores , Cicloeximida/farmacologia , Dactinomicina/farmacologia , Relação Dose-Resposta a Droga , Indução Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico/genética , Humanos , Imidazóis/farmacologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Inibidores da Síntese de Ácido Nucleico/farmacologia , Fosforilação/efeitos dos fármacos , Proteína Quinase C/metabolismo , Inibidores da Síntese de Proteínas , Piridinas/farmacologia , Pirrolidinas/farmacologia , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Tiocarbamatos/farmacologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno
18.
Life Sci ; 72(2): 113-24, 2002 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-12417245

RESUMO

We previously showed that a dissociated form of a low-molecular-weight heat shock-related protein 20 (HSP20) but not an aggregated form of HSP20 suppresses platelet aggregation. In the present study, we investigated the behavior of HSP20 in response to endothelial injury and the possible mechanism of HSP20 in platelet functions. The levels of HSP20 in vessel wall after endothelial injury were markedly reduced. This observation was supported by the results of Western blotting analysis and immunohistochemical analysis. Additionally, the plasma levels of HSP20 in cardiomyopathic hamsters were markedly elevated. Centrifugation on sucrose density gradients allowed detection mainly of the dissociated form of plasma HSP20 in these hamsters. Human platelets showed specific binding sites for HSP20. Moreover, HSP20 markedly reduced thrombin-induced phosphoinositide hydrolysis by phospholipase C in human platelets. Taken together, our results strongly suggest that HSP20, which immediately responds to pathological events, acts extracellularly as a regulator of platelet functions.


Assuntos
Plaquetas/fisiologia , Proteínas de Choque Térmico/fisiologia , Fosfoproteínas/fisiologia , Animais , Sítios de Ligação , Plaquetas/enzimologia , Western Blotting , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Artérias Carótidas/patologia , Cricetinae , Endotélio Vascular/lesões , Endotélio Vascular/patologia , Espaço Extracelular/fisiologia , Proteínas de Choque Térmico HSP20 , Proteínas de Choque Térmico/metabolismo , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Inositol/metabolismo , Masculino , Miocárdio/química , Miocárdio/patologia , Fosfatidilinositóis/metabolismo , Fosfoproteínas/metabolismo , Testes de Função Plaquetária , Trombina/antagonistas & inibidores , Trombina/química , Fosfolipases Tipo C/sangue
19.
Oral Oncol ; 39(3): 301-5, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12618204

RESUMO

The long-term follow-up case of monostotic fibrous dysplasia of the maxilla in a 10-year-old girl is described with her endocrinologic data and therapeutic consequence of calcitonin administration in association with surgical interventions. The fibrous dysplasia tends to become more quiescent or static after skeletal growth ceases, but the causative has been still unknown to date. In this case reported changes of calciotropic hormones in the serum were well corresponding to the ceasing of the tumor growth at the puberty and reflected to the calcitonin administration. Although calcitonin has been applied to the fibrous dysplasia associated with McCune Albright syndrome, no histologic changes have been described after the calcitonin treatment. This report might be the first description of bone remodeling after the calcitonin treatment for the fibrous dysplasia of the maxilla in immature people. Data of this case may provide a clue to the pathogenesis of fibrous dysplasia. Surgical intervention can be performed after the local bone calcification by a calcitonin treatment, because of alleviation of vigorous hemorrhage by the bone remodeling.


Assuntos
Remodelação Óssea/efeitos dos fármacos , Calcitonina/uso terapêutico , Displasia Fibrosa Monostótica/tratamento farmacológico , Maxila/fisiopatologia , Criança , Feminino , Displasia Fibrosa Monostótica/diagnóstico por imagem , Displasia Fibrosa Monostótica/fisiopatologia , Seguimentos , Humanos , Radiografia
20.
Eur J Radiol ; 83(3): e137-46, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24377674

RESUMO

Palatal tumors commonly arise from the minor salivary glands, and benign tumors account for approximately half of all minor salivary gland tumors. Minor salivary gland tumors have an affinity for the posterior hard palate and soft palate and virtually never arise in the midline, probably because of the distribution of palatal salivary glands. The majority of benign salivary gland tumors of the palate are pleomorphic adenomas, while the most common malignant salivary gland tumor is adenoid cystic carcinoma, followed by mucoepidermoid carcinoma, adenocarcinoma, and polymorphous low-grade adenocarcinoma. Epithelial tumors frequently arise from the soft palate. The majority of benign epithelial tumors of the palate are papillomas, while most malignant epithelial tumors are squamous cell carcinomas. Various types of mesenchymal tumors, including fibromas, lipomas, schwannomas, neurofibromas, hemangiomas, and lymphangiomas, also involve the palate. This article describes the CT and MR findings of benign and malignant palatal tumors.


Assuntos
Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias Palatinas/diagnóstico , Posicionamento do Paciente/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade
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