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This study evaluated the mechanical properties of demineralized dentin matrix submitted to different bleaching treatments, as well as the changes in mass and collagen biodegradation brought about by endogenous protease. Dentin collagen matrices were prepared to receive the following treatments (n=12): no bleaching treatment (C-control), 10% carbamide peroxide (CP-Opalescence PF, Ultradent, South Jordan, UT, USA) 10%/8 hours/day/14 days, and 40% hydrogen peroxide (HP-Opalescence Boost, Ultradent), 40 minutes per session/3 sessions. The dentin matrices were evaluated for elastic modulus and mass before and after treatments and ultimate tensile strength after treatments. The solution collected during storage was evaluated for hydroxyproline release. There was no statistically significant difference between CP and C in terms of the elastic modulus (p=0.3697) or mass variation (p=0.1333). Dentin beams treated with HP and C presented significant mass loss after the first session (p=0.0003). HP treatment led to complete degradation of collagen matrices after the second bleaching session. After the second session, CP showed higher hydroxyproline concentration than C (p<0.0001). Ultimate tensile strength was lower for CP than C (p=0.0097). CP did not affect the elastic modulus or the dentin collagen matrix mass but did promote hydroxyproline release by endogenous protease and reduce the ultimate tensile strength. HP significantly affected the mechanical properties of dentin and promoted complete degradation of the demineralized dentin collagen matrix.
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Studying the gravity-dependent characteristics of regolith, fine-grained granular media covering extra-terrestrial bodies is essential for the reliable design and analysis of landers and rovers for space exploration. In this study, we propose an experimental approach to examine a granular flow under stable artificial gravity conditions for a long duration generated by a centrifuge at the International Space Station. We also perform a discrete element simulation of the granular flow in both artificial and natural gravity environments. The simulation results verify that the granular flows in artificial and natural gravity are consistent. Further, regression analysis of the experimental results reveals that the mass flow rate of granular flow quantitatively follows a well-known physics-based law with some deviations under low-gravity conditions, implying that the bulk density of the granular media decreases with gravity. This insight also indicates that the bulk density considered in simulation studies of space probes under low-gravity conditions needs to be tuned for their reliable design and analysis.
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OBJECTIVE: To investigate the effect of calcium-phosphate-based desensitizers, Teethmate AP paste (TMAP) and Teethmate Desensitizer (TMD) (Kuraray Noritake Dental, Tokyo, Japan), on the prevention of staining on acid-eroded enamel. METHODS AND MATERIALS: Forty polished enamel samples (4×4×1 mm) from bovine incisors were randomly divided into five groups (n=8). After immersion in 50 mL of 0.5% citric acid (pH 2.5) for 15 minutes to form acid-eroded surfaces, the surfaces were subjected to different treatments with TMAP, TMD, and NaF (0.21% means 950 ppm) for five minutes. Another eroded group was not treated with desensitizer. For the control group, the samples were not eroded or treated. All the samples were stored in artificial saliva (AS) at pH 7.2 for 24 hours at 37°C. The TMAP, TMD, or NaF was reapplied at eight and 16 hours during the 24 hours of storage time. The surface roughness (Sa) was evaluated following ISO 25178 for surface texture using confocal laser scanning microscopy (VK-X 150 series, Keyence, Osaka, Japan) before acid erosion, after acid erosion, and after 24 hours of incubation in AS. Afterward, the color difference was measured with a dental colorimeter (Shade Eye NCC, Shofu, Kyoto, Japan) before and after staining with tea solution. RESULTS: One-way repeated measures analysis of variance showed that acid erosion significantly increased Sa (p<0.001). TMAP- and TMD-treated groups exhibited lower Sa values than the NaF group and the no-desensitizer treatment group. The greatest staining was observed in the NaF group and the no-desensitizer group, while the TMAP and TMD groups significantly decreased the formation of stains. CONCLUSIONS: Acid-eroded enamel increased surface roughness and tended to absorb more stains. However, the application of TMAP and TMD moderated the roughness and thus prevented the formation of extrinsic stains.
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Erosão Dentária , Animais , Cálcio , Bovinos , Esmalte Dentário , Japão , Coloração e RotulagemRESUMO
Before the accident at Fukushima Daiichi nuclear power plant in March 2011, I never thought about radiation. After the accident, I originally evacuated with my two sons, but we returned home a few weeks later to be with my husband and parents-in-law as I felt that life with my family was what mattered and the very basis of my happiness. Today, 5 years after the accident, some people are able to think positively about the situation, and some remain uncertain. This article offers my experience and thoughts as a mother to help enable others to feel less stressed about eating food produced in Fukushima, and suggests ideas to help lift their spirits.
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Acidente Nuclear de Fukushima , Criança , Humanos , Japão , Proteção RadiológicaRESUMO
Dendritic cell (DC) migration to regional lymph nodes (RLNs) is an essential step in adaptive immunity, and cell-surface antigens on migrating DCs greatly affect the quality and quantity of subsequent immune responses. Although MHC class II(+) DC-like cells exist in the dental pulp, the lineage and function of these cells remain unknown. Here, we identified migratory DCs from the dental pulp after cusp trimming and acid etching in KikGR mice, in which the photoconvertible fluorescent protein changed from green to red upon violet light exposure. Two major cell fractions from the dental pulp had migrated to the RLNs at 16 hrs after cusp treatment, which showed the following lineage markers in the main and second fractions: CD11c(high)CD11b(++)Ly6C(low) Ly6G(low) F4/80(+) and CD11c(med)CD11b(+++)Ly6C(++)Ly6G(+++)F4/80(-), respectively. These lineage markers indicate that the former cells were DCs that had migrated through afferent lymphoid vessels, and the latter were granulocytes recruited via blood circulation. Migratory dental pulp DCs were mature, expressing the highest levels of CD273 (B7-DC) and CD86 co-stimulators and MHC class II. Our results suggest that cariogenic-bacteria-exposed dental pulp DCs migrate to RLNs and there trigger adaptive immune responses.
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Células Dendríticas/imunologia , Polpa Dentária/citologia , Linfonodos/imunologia , Condicionamento Ácido do Dente/métodos , Imunidade Adaptativa/imunologia , Animais , Antígenos de Diferenciação/análise , Antígenos de Diferenciação Mielomonocítica/análise , Antígenos Ly/análise , Antígeno B7-2/análise , Antígeno CD11b/análise , Antígeno CD11c/análise , Linhagem da Célula/imunologia , Movimento Celular/imunologia , Feminino , Corantes Fluorescentes , Técnicas de Introdução de Genes , Antígenos de Histocompatibilidade Classe II/análise , Glicoproteínas de Membrana/análise , Camundongos , Camundongos Endogâmicos BALB C , Proteína 2 Ligante de Morte Celular Programada 1/análise , Preparo do Dente/métodosRESUMO
Bioglass 45S5 is a silica-based bioactive glass capable of depositing a layer of hydroxyl carbonate apatite on the surface of the glass when immersed in body fluids. The present paper studies a new technique for treating early human dental enamel caries lesions by using a paste composed of 45S5 bioglass and phosphoric acid. Artificial caries lesions were induced in enamel flat surfaces by means of a decalcification solution. All specimens were exposed to a brushing-abrasion challenge to test the durability of any newly formed layer resulting from the application of 45S5 bioglass paste. The specimens treated with bioglass paste showed complete coverage with a layer of brushite crystals. The brushing-abrasion challenge did not statistically affect the percentage of enamel coverage with the crystalline layer formed by the application of bioglass (p<0.05). These crystals were converted to hydroxyapatite crystals when stored in artificial saliva for 14 days. The current technique suggests the possibility of restoring incipient enamel erosive lesion with an abrasion durable layer of hydroxyapatite crystals.
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Cerâmica/farmacologia , Esmalte Dentário/química , Desmineralização do Dente/terapia , Fosfatos de Cálcio/química , Materiais Revestidos Biocompatíveis , Cárie Dentária/terapia , Durapatita/química , Vidro , Humanos , Técnicas In Vitro , Teste de Materiais , Dente Molar , Saliva Artificial , Propriedades de Superfície , Fatores de Tempo , Difração de Raios XRESUMO
AIM: To evaluate the influence of reduced glutathione (GSH) application on 2-hydroxyethylmethacrylate (HEMA) cytotoxicity on rat pulpal cells and evaluate the effect of etched-dentine treatment with GSH on the immediate microtensile bond strength (µTBS) of etch-and-rinse adhesive. METHODOLOGY: The cytotoxicity of 10 mmol L(-1) HEMA, 10 mmol L(-1) HEMA + 1 mmol L(-1) GSH, 10 mmol L(-1) HEMA + 5 mmol L(-1) GSH and 10 mmol L(-1) HEMA + 10 mmol L(-1) GSH was compared (6 h and 24 h). Cells viability was measured by means of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, followed by morphological observation of cells. Etched-dentine surfaces were rinsed and treated with one of the following solutions: 2% GSH, 5% GSH or 10% GSH, bonded with Adper Single Bond Plus (3M, ESPE, St. Paul, MN, USA) and restored with resin composite. The control group received no GSH treatment. After 1 day of water-storage at 37 °C, the specimens were subjected to µTBS testing. Cytotoxicity and µTBS data were analysed by one-way anova and Tukey post hoc tests (P < 0.05). RESULTS: There were significant differences between the groups. HEMA elicited a remarkable toxic effect. 10 mmol L(-1) GSH prevented HEMA-induced damage at both exposure times. Whilst 5 mmol L(-1) GSH lost its protective effect at 24-h exposure time and 1 mmol L(-1) GSH showed no protective effect at both exposure times, GSH had no significant effect on the immediate µTBS; however, 5% GSH had higher bond strength value when compared to 10% GSH (P = 0.003). CONCLUSION: Controlled concentrations of GSH had a protective effect against HEMA cytotoxicity. GSH had neither positive nor negative influence on µTBS.
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Polpa Dentária/citologia , Dentina/química , Glutationa/farmacologia , Metacrilatos/química , Cimentos de Resina/química , Animais , Linhagem Celular , Humanos , RatosRESUMO
Preservation of natural tooth structure requires early detection of the carious lesion and is associated with comprehensive patient dental care. Processes aiming to detect carious lesions in the initial stage with optimum efficiency employ a variety of technologies such as magnifying loupes, transillumination, light and laser fluorescence (QLF® and DIAGNOdent® ) and autofluorescence (Soprolife® and VistaCam®), electric current/impedance (CarieScan(®) ), tomographic imaging and image processing. Most fluorescent caries detection tools can discriminate between healthy and carious dental tissue, demonstrating different levels of sensitivity and specificity. Based on the fluorescence principle, an LED camera (Soprolife® ) was developed (Sopro-Acteon, La Ciotat, France) which combined magnification, fluorescence, picture acquisition and an innovative therapeutic concept called light-induced fluorescence evaluator for diagnosis and treatment (LIFEDT). This article is rounded off by a Soprolife® illustration about minimally or even non-invasive dental techniques, distinguishing those that preserve or reinforce the enamel and enamel-dentine structures without any preparation (MIT1- minimally invasive therapy 1) from those that require minimum preparation of the dental tissues (MIT2 - minimally invasive therapy 2) using several clinical cases as examples. MIT1 encompasses all the dental techniques aimed at disinfection, remineralizing, reversing and sealing the caries process and MIT2 involves a series of specific tools, including microburs, air abrasion devices, sonic and ultrasonic inserts and photo-activated disinfection to achieve minimal preparation of the tooth. With respect to minimally invasive treatment and prevention, the use of lasers is discussed. Furthermore, while most practices operate under a surgical model, Caries Management by Risk Assessment (CaMBRA) encourages a medical model of disease prevention and management to control the manifestation of the disease, or keep the oral environment in a state of balance between pathological and preventive factors. Early detection and diagnosis and prediction of lesion activity are of great interest and may change traditional operative procedures substantially. Fluorescence tools with high levels of magnification and observational capacity should guide clinicians towards a more preventive and minimally invasive treatment strategy.
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Assistência Odontológica/tendências , Testes de Atividade de Cárie Dentária/métodos , Cárie Dentária/terapia , Cárie Dentária/diagnóstico , Testes de Atividade de Cárie Dentária/instrumentação , Diagnóstico Precoce , Humanos , Tratamentos com Preservação do Órgão/métodos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: Phosphoric acid-Bioglass 45S5 paste can create an interaction layer formed of calcium-phosphate crystals on the dentin surface. In this study, the efficiency of decreasing the dentin permeability exerted by the interaction layer formed between bioglass and dentin was compared to a resin-containing oxalate desensitizing agent (MS Coat One) and a resin-free oxalate desensitizing agent (Super Seal). METHODS: Dentin permeability was measured before/after a brushing abrasion challenge, followed by examining the top and the fractured dentin surfaces with a field emission scanning electron microscope. Moreover, the chemical nature of the compounds formed on top of the dentin surface was examined using the field emission scanning electron microscope (FE-SEM) equipped with an energy-dispersive X-ray spectroscope (EDS), and the crystalline structures of the dentinal surfaces were examined by X-ray diffraction (XRD). RESULTS: The results showed that application of 45S5 bioglass paste to dentin was able to occlude patent dentinal tubule orifices with a layer of calcium-phosphate crystals, while the oxalate containing agents were able to form small crystals which were found in dentinal tubule orifices and scattered along the superficial parts of the dentinal tubule lumen. The brushing-abrasion challenge significantly increased the permeability of dentin treated by Super Seal and MS Coat One, while these challenges had no significant effect on the dentin permeability of specimens treated with 45S5 bioglass paste. SIGNIFICANCE: The new technique provided better durability than two products available on the market. Moreover, our previous research showed the biocompatibility of using this technique on dental pulp cells, suggesting that this technique can aid in treating dentin hypersensitivity cases.
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Cerâmica/química , Dessensibilizantes Dentinários/química , Permeabilidade da Dentina/fisiologia , Sensibilidade da Dentina/terapia , Dentina/química , Vidro/química , Oxalatos/química , Ácidos Fosfóricos , Materiais Biocompatíveis , Dessensibilizantes Dentinários/uso terapêutico , Sensibilidade da Dentina/prevenção & controle , Humanos , Microscopia Eletrônica de Varredura , Espectrometria por Raios X , Estatísticas não Paramétricas , Propriedades de Superfície , Difração de Raios XRESUMO
Functional monomers in dentin adhesives are involved in wetting dental substrates, demineralization, and the formation of calcium salts. However, the interaction of these monomers with collagen is not understood at a molecular/atomic level. We performed saturation transfer difference (STD) NMR spectroscopy to investigate the binding interaction of 2 functional monomers, 4-methacryloyloxyethyl trimellitate anhydride (4-META) and 10-methacryloyloxydecyl dihydrogenphosphate (MDP), with atelocollagen as a triple-helical peptide model. High STD intensities were detected on the protons in the aliphatic region in MDP, whereas they were not detected for 4-META. The STD results imply that MDP has a relatively stable interaction with the collagen, because of the hydrophobic interactions between the hydrophobic MDP moieties and the hydrophobic collagen surface. This finding indicates that MDP-collagen complexation accounts for stable dentin bonding.
Assuntos
Colágeno/química , Colagem Dentária , Adesivos Dentinários/química , Espectroscopia de Ressonância Magnética/métodos , Metacrilatos/química , Cimentos de Resina/química , Mapeamento de Epitopos/métodos , Interações Hidrofóbicas e Hidrofílicas , Ligantes , PrótonsRESUMO
We study the protocol dependence of the mechanical properties of granular media by means of computer simulations. We control a protocol of realizing disk packings in a systematic manner. In 2D, by keeping material properties of the constituents identical, we carry out compaction with various strain rates. The disk packings exhibit the strain rate dependence of the critical packing fraction above which the pressure becomes non-zero. The observed behavior contrasts with the well-studied jamming transitions for frictionless disk packings. We also observe that the elastic moduli of the disk packings depend on the strain rate logarithmically. Our results suggest that there exists a time-dependent state variable to describe macroscopic material properties of disk packings, which depend on its protocol.
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OBJECTIVES: Caries progress might be controlled when collagen matrix could be preserved after demineralization. The aim of this pH cycling study was to investigate the effect of hesperidin, a citrus flavonoid antioxidant, on dentine collagen and remineralization in dentine lesion, and compared with that of chlorhexidine. METHODS: The pH cycling was employed on bovine root dentine by demineralization for 14 h, incubation in testing solutions (hesperidin or chlorhexidine) for 2 h and remineralization with bacteria-derived collagenase for 8 h, for 8 days. Calcium release was measured by means of an atomic absorption spectrophotometer, and degraded collagen matrix by collagenase was investigated by assaying hydroxyproline. The lesion depth and mineral loss was evaluated by means of transverse microradiography. RESULTS: The effect of testing solutions had a significant difference on the results of chemical analyses (p<0.0115 for calcium release; p<0.0008 for degradated collagen). The lesion depth and mineral loss were reduced in the lesions where were incubated with hesperidin and chlorhexidine. The remineralization in deep lesions was found when the matrix was incubated in hesperidin, whilst no mineral uptake in deep lesion when incubated in chlorhexidine. CONCLUSION: Hesperidin preserved collagen and inhibited demineralization, and enhanced remineralization even under the fluoride-free condition.
Assuntos
Antioxidantes/farmacologia , Colágeno/efeitos dos fármacos , Dentina/efeitos dos fármacos , Hesperidina/farmacologia , Desmineralização do Dente/prevenção & controle , Raiz Dentária/efeitos dos fármacos , Animais , Anti-Infecciosos Locais/uso terapêutico , Cálcio/análise , Bovinos , Clorexidina/farmacologia , Cromatografia Líquida de Alta Pressão , Colágeno/análise , Colagenases/farmacologia , Dentina/patologia , Concentração de Íons de Hidrogênio , Hidroxiprolina/análise , Teste de Materiais , Colagenase Microbiana , Microrradiografia , Espectrofotometria Atômica , Temperatura , Fatores de Tempo , Remineralização Dentária/métodos , Raiz Dentária/patologiaRESUMO
Bioglass 45S5 is a bioactive glass that can create a layer of calcium-phosphate crystals on mineralized hard tissues. In this study, 45S5 bioglass was mixed with phosphoric acid and irradiated with CO(2) laser and examined as a possible aid in the treatment of dentin hypersensitivity. The dentinal surface modified by the aforementioned technique was chemically and micro-morphologically examined with a field emission scanning electron microscope (FE-SEM) equipped with an energy-dispersive x-ray spectroscope (EDS), and the crystalline structures of the examined dentinal surfaces were examined by x-ray diffraction (XRD). Moreover, the mechanical properties of the newly formed layer were examined by nanoindentation. The results showed that 45S5 bioglass could occlude the dentinal tubule orifices with calcium-phosphate crystals. The application of CO(2) laser potentially improved the mechanical organization of these crystals.
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Cerâmica/uso terapêutico , Dessensibilizantes Dentinários/uso terapêutico , Sensibilidade da Dentina/tratamento farmacológico , Dentina , Lasers de Gás/uso terapêutico , Fosfatos de Cálcio , Cristalografia por Raios X , Dentina/química , Dentina/ultraestrutura , Módulo de Elasticidade , Vidro , Dureza , Humanos , Microscopia Eletrônica de Varredura/instrumentação , Espectrometria por Raios X , ÁguaRESUMO
Although inflammation is an important component of atherosclerosis, it is unknown whether inhaled corticosteroids (ICS) as anti-inflammatory drugs prevent atherosclerosis. In the present study, carotid atherosclerosis was evaluated by ultrasonography in 150 asthmatic patients who had been regularly treated with ICS, and in 150 matched nonasthmatic controls, with an assessment of atherosclerotic risk factors. Carotid intima-media thickness was significantly lower in the asthmatic patients than in the controls. The prevalence of carotid plaque tended to be lower in the asthmatic patients than in the controls. Defined carotid atherosclerosis was diagnosed in 51 of the asthmatic patients, who were older, with a higher prevalence of males, a higher prevalence of dyslipidaemia and a lower mean daily dose of ICS than the 99 patients without carotid atherosclerosis. Stepwise multiple logistic regression analysis identified age, male sex and dyslipidaemia as positive risk factors for carotid atherosclerosis. The mean daily dose of ICS was a negative risk factor. Carotid atherosclerosis is reduced in asthmatic patients treated with ICS compared with matched controls. This study suggests that ICS may have protective effects against atherosclerosis.
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Corticosteroides/uso terapêutico , Asma/complicações , Asma/tratamento farmacológico , Doenças das Artérias Carótidas/complicações , Idoso , Anti-Inflamatórios/uso terapêutico , Doenças das Artérias Carótidas/fisiopatologia , Dislipidemias/patologia , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Prevalência , Análise de Regressão , Fatores de Risco , Resultado do TratamentoRESUMO
To treat metabolic syndrome, fat tissue dysfunction should be corrected rather than controlling conventional risk factors such as hypertension, dyslipidemia, and diabetes mellitus. For this purpose, accumulating evidence suggests increasing plasma adiponectin levels can be a key treatment strategy, especially in setting of food or drug selection. Here we report that adipocyte precursors obtained from several sites of fat tissue, which we call Metabolic Stem Cells (MSC), could be used as a novel screening system to identify adiponectin enhancing drugs or food for individual patients. MSC were prepared from fat tissues collected from 29 patients. They were differentiated in cultures into mature adipocytes. The time course of adiponectin production was independent of the number of mature adipocytes and gradually decreased at 48 h after differentiation. Pioglitazone, a full PPARgamma agonist, stabilized adiponectin production at days 8-16 after differentiation, whereas telmisartan, a partial PPARgamma agonist, showed variable response. Dividing the adiponectin secretion of day 12 by that of day 10 provided an estimate of adiponectin-producing activity irrespective of the number of MSC-derived adipocytes in culture. Using this score of adiponectin-production activity, we successfully assessed 16 agents in a 96-well plate. The effect of each agent on adiponectin production showed a similar pattern, independent of the site of isolated adipose tissue. Our results show that MSC can be used as a tool for selecting drugs that enhance adiponectin-production activity.
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Adiponectina/biossíntese , Diferenciação Celular/fisiologia , Células-Tronco/metabolismo , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adiponectina/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Cultivadas , Feminino , Transportador de Glucose Tipo 4/biossíntese , Transportador de Glucose Tipo 4/genética , Humanos , Masculino , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , PPAR gama/genética , RNA/biossíntese , RNA/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células-Tronco/efeitos dos fármacosRESUMO
BACKGROUND AND PURPOSE: The effects of statins on diabetes mellitus (DM) are controversial, and their effects on pancreatic fibrosis are poorly defined. We investigated the effect of long- and short-term treatments with pravastatin on the development of DM and pancreatic fibrosis in DM-prone Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats. EXPERIMENTAL APPROACH: Male OLETF rats were divided into four groups at 12 weeks of age. The first group received a standard rat diet until the end of the experimental period at age 80 weeks. The second group was given a diet containing 0.05% pravastatin from 12 weeks of age, before the onset of DM and pancreatic fibrosis, and the third group was given the same pravastatin diet from 28 weeks of age, after the onset of DM and pancreatic fibrosis, until age 80 weeks. The fourth group received the same pravastatin diet only for 16 weeks, from 12 to 28 weeks of age, and switched to a standard diet. Progressions of DM and pancreatic fibrosis were evaluated. KEY RESULTS: Long-term treatments with pravastatin, either from 12 or 28 weeks of age, decreased serum glucose concentration and fibrotic area, elevated superoxide dismutase activity and down-regulated transforming growth factor-beta1 mRNA in the pancreas. In contrast, after a short-term treatment with pravastatin, these parameters markedly deteriorated after its cessation. CONCLUSIONS AND IMPLICATIONS: The results suggest that long-term treatment with pravastatin improves DM and pancreatic fibrosis via anti-oxidative and anti-fibrotic properties, whereas cessation of pravastatin abolishes these beneficial effects, and accelerates DM and pancreatic fibrosis.
Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pâncreas/efeitos dos fármacos , Pravastatina/uso terapêutico , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/patologia , Animais , Apoptose/efeitos dos fármacos , Glicemia/análise , Colesterol/sangue , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Ácidos Graxos não Esterificados/sangue , Fibrose , Insulina/sangue , Resistência à Insulina , Masculino , Tamanho do Órgão/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/patologia , Peroxidase/metabolismo , Ratos , Ratos Long-Evans , Superóxido Dismutase/metabolismo , Fatores de Tempo , Fator de Crescimento Transformador beta1/biossíntese , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/biossínteseRESUMO
BACKGROUND: Smad6 is implicated in the inhibition of bone morphogenetic protein signalling. However, the function of Smad6 in the pancreas remains obscure. METHODS: To elucidate the unknown function of Smad6, we developed transgenic mice selectively expressing Smad6 in pancreatic acinar cells using a plasmid construct coding rat elastase 1 enhancer/promoter. RESULTS: Smad6 transgenic mice had no specific distinguishing phenotype such as body weight, pancreatic wet weight and concentrations of pancreatic protein. However, Smad6 transgenic mice reacted to hyperstimulation by caerulein injection or a diet containing 0.5% ethionine. Maximal amylase release stimulated by CCK-8 was significantly decreased in Smad6 transgenic mice acini, and trypsin activities in transgenic mice acini were significantly increased after stimulation of CCK-8. There was no difference in effect of CCK-8 stimulation on the subsequent increase in intracellular free Ca2+ concentration ([Ca2+](i)) between wild-type and transgenic mice acini. These findings suggest that reduced pancreatic enzyme secretion was caused by the disorder of its downstream signal transduction pathways in acinar cells. The amino acid sequence at the N-terminus of Smad6 was similar to that of synaptosome-associated protein (SNAP) 25 interacting protein, which plays an important role in regulating exocytosis of pancreatic enzymes in acinar cells. Pancreatic SNAP25 protein levels in transgenic mice were decreased after caerulein-induced pancreatitis. CONCLUSIONS: These results suggest that elevated expression of Smad6 inhibits normal function of SNAP25-interacting protein and SNAP25, reduces amylase secretion in acinar cells, and increases the susceptibility of acinar cells to the onset of pancreatitis.
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Pancreatite/metabolismo , Proteína Smad6/fisiologia , Doença Aguda , Sequência de Aminoácidos , Amilases/metabolismo , Animais , Ceruletídeo , Modelos Animais de Doenças , Progressão da Doença , Predisposição Genética para Doença , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Dados de Sequência Molecular , Pâncreas Exócrino/metabolismo , Pancreatite/induzido quimicamente , Pancreatite/patologia , Fenótipo , RNA Mensageiro/genética , Alinhamento de Sequência , Proteína Smad6/genética , Proteína Smad6/metabolismo , Proteína 25 Associada a Sinaptossoma/genética , Fator de Crescimento Transformador beta1/biossíntese , Fator de Crescimento Transformador beta1/sangue , Fator de Crescimento Transformador beta1/genética , Regulação para CimaRESUMO
BACKGROUND AND STUDY AIM: Endoscopic mucosal resection using a cap (EMR-C) is an established method for curative resection of early neoplastic lesions; prelooping of the snare may however be difficult and lead to imprecise resection. We therefore compared two modifications of the conventional technique using outer snare placement with an accessory channel in a prospective, nonrandomized study. PATIENTS AND METHODS: Between October 2004 and March 2007, 54 patients (men 37, women 17; mean age 71 years) underwent EMR. One method involved an internally retained snare (IRS) cap, with a fixed prelooped snare inside the cap; the other method used an externally guided snare (EGS) cap with the snare guided over an oblique cap. The main outcome parameters were specimen size, en bloc resection, and complications. RESULTS: There was no difference between use of the IRS and EGS cap methods in relation to specimen size (27.6 vs. 27.1 mm), or rates of en bloc resection (88.9 % vs. 83.3 %); only one perforation occurred, and this was in the EGS group. CONCLUSION: Both techniques appeared to provide similar efficacy, the inner rim of the IRS cap stabilizes aspiration of the lesion compared with the EGS cap that does not have it.