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Cytochrome P450 1A1 (CYP1A1) catalyzes the metabolic activation of polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (B[a]P) and is transcriptionally regulated by the aryl hydrocarbon receptor (AhR)/AhR nuclear translocator (ARNT) complex upon exposure to PAHs. Accordingly, inhibition of CYP1A1 expression reduces production of carcinogens from PAHs. Although transcription of the CYP1A1 gene is known to be repressed by transforming growth factor-ß (TGF-ß), how TGF-ß signaling is involved in the suppression of CYP1A1 gene expression has yet to be clarified. In this study, using mammalian cell lines, along with shRNA-mediated gene silencing, CRISPR/Cas9-based genome editing, and reporter gene and quantitative RT-PCR assays, we found that TGF-ß signaling dissociates the B[a]P-mediated AhR/ARNT heteromeric complex. Among the examined Smads, Smad family member 3 (Smad3) strongly interacted with both AhR and ARNT via its MH2 domain. Moreover, hypoxia-inducible factor 1α (HIF-1α), which is stabilized upon TGF-ß stimulation, also inhibited AhR/ARNT complex formation in the presence of B[a]P. Thus, TGF-ß signaling negatively regulated the transcription of the CYP1A1 gene in at least two different ways. Of note, TGF-ß abrogated DNA damage in B[a]P-exposed cells. We therefore conclude that TGF-ß may protect cells against carcinogenesis because it inhibits CYP1A1-mediated metabolic activation of PAHs as part of its anti-tumorigenic activities.
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Citocromo P-450 CYP1A1/genética , Receptores de Hidrocarburo de Aril/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Células A549 , Animales , Translocador Nuclear del Receptor de Aril Hidrocarburo/genética , Translocador Nuclear del Receptor de Aril Hidrocarburo/metabolismo , Benzo(a)pireno/toxicidad , Células COS , Chlorocebus aethiops , Citocromo P-450 CYP1A1/metabolismo , Expresión Génica/genética , Regulación de la Expresión Génica/genética , Células HEK293 , Humanos , Factor 1 Inducible por Hipoxia/metabolismo , Hidrocarburos Policíclicos Aromáticos/metabolismo , Pirenos , Transducción de Señal , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta/fisiologíaRESUMEN
INTRODUCTION: Acute otitis media is a highly prevalent disease in children. Although guidelines in many countries recommend amoxicillin as the first-line treatment for acute otitis media, the prescribing pattern in Japan is not clear. Our objective was to clarify the amoxicillin prescriptions as first-line antibiotics for acute otitis media and factors associated with amoxicillin prescriptions. Also, changes in amoxicillin prescriptions during the study period by medical facilities were investigated. METHODS: Using an administrative claims database, we included new episodes of acute otitis media prescribed antibiotics in children under seven years of age between 2014 and 2018. The proportion of amoxicillin prescription was described. Using multivariate logistic regression analysis, factors associated with amoxicillin prescription were evaluated. Rate differences were calculated to describe changes in amoxicillin prescription by medical facilities. RESULTS: 207,213 episodes in 149,929 patients were identified. Amoxicillin prescription was 24.0% and increased over the study period (P for trend <0.001). Characteristics of medical facilities were associated with amoxicillin prescriptions, and hospitals were more likely to prescribe amoxicillin (adjusted odds ratio: 1.71, 95% confidence intervals: 1.63 to 1.79). Compared to 2014, the range of increase in amoxicillin prescription in 2018 was greater in hospitals (14.9%) and pediatric clinics (10.5%) than in otolaryngology clinics (5.9%) and other specialty clinics (6.0%). CONCLUSIONS: During the study period, amoxicillin prescriptions had increased compared to 2014, but the proportion was still low. Clinics prescribed less amoxicillin than hospitals, and the range of increase was small. Our results suggested that some interventions focused on clinics are needed.
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Antibacterianos , Otitis Media , Enfermedad Aguda , Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Niño , Humanos , Lactante , Japón/epidemiología , Otitis Media/tratamiento farmacológico , Otitis Media/epidemiología , Pautas de la Práctica en Medicina , PrescripcionesRESUMEN
We investigated the effectiveness of using Carr's flowability index (FI) and practical angle of internal friction (Φ) as indexes for setting the target Mg-St mixing time needed for preparing tablets with the target physical properties. We used FI as a measure of flowability under non-loaded conditions, and Φ as a measure of flowability under loaded conditions for pharmaceutical powders undergoing direct compression with varying concentrations of Mg-St and mixing times. We evaluated the relationship between Mg-St mixing conditions and pharmaceutical powder flowability, analyzed the correlation between the physical properties of the tablets (i.e., tablet weight variation, drug content uniformity, hardness, friability, and disintegration time of tablets prepared using the pharmaceutical powder), and studied the effect of Mg-St mixing conditions and pharmaceutical powder flowability on tablet properties. Mg-St mixing time highly correlated with pharmaceutical powder FI (R 2 = 0.883) while Mg-St concentration has low correlation with FI, and FI highly correlated with the physical properties of the tablet (R 2 values: weight variation 0.509, drug content variation 0.314, hardness 0.525, friability 0.477, and disintegration time 0.346). Therefore, using pharmaceutical powder FI as an index could enable prediction of the physical properties of a tablet without the need for tableting, and setting the Mg-St mixing time by using pharmaceutical powder FI could enable preparation of tablets with the target physical properties. Thus, the FI of the intermediate product (i.e., pharmaceutical powder) is an effective index for controlling the physical properties of the finished tablet.
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Comprimidos , Tecnología Farmacéutica , Dureza , Lubricantes , Polvos/química , Factores de TiempoRESUMEN
Recent generation of induced pluripotent stem (iPSCs) has made a significant impact on the field of human regenerative medicine. Prior to the clinical application of iPSCs, testing of their safety and usefulness must be carried out using reliable animal models of various diseases. In order to generate iPSCs from common marmoset (CM; Callithrix jacchus), one of the most useful experimental animals, we have lentivirally transduced reprogramming factors, including POU5F1 (also known as OCT3/4), SOX2, KLF4, and c-MYC into CM fibroblasts. The cells formed round colonies expressing embryonic stem cell markers, however, they showed an abnormal karyotype denoted as 46, X, del(4q), +mar, and formed human dysgerminoma-like tumors in SCID mice, indicating that the transduction of reprogramming factors caused unexpected tumorigenesis of CM cells. Moreover, CM dysgerminoma-like tumors were highly sensitive to DNA-damaging agents, irradiation, and fibroblast growth factor receptor inhibitor, and their growth was dependent on c-MYC expression. These results indicate that DNA-damaging agents, irradiation, fibroblast growth factor receptor inhibitor, and c-MYC-targeted therapies might represent effective treatment strategies for unexpected tumors in patients receiving iPSC-based therapy.
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Carcinogénesis/genética , Disgerminoma/terapia , Células Madre Pluripotentes Inducidas , Cariotipo Anormal , Animales , Callithrix , Disgerminoma/genética , Disgerminoma/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/biosíntesis , Factores de Transcripción de Tipo Kruppel/genética , Lentivirus , Ratones , Factor 3 de Transcripción de Unión a Octámeros/biosíntesis , Factor 3 de Transcripción de Unión a Octámeros/genética , Proteínas Proto-Oncogénicas c-myc/biosíntesis , Proteínas Proto-Oncogénicas c-myc/genética , Factores de Transcripción SOXB1/biosíntesis , Factores de Transcripción SOXB1/genética , Transducción GenéticaRESUMEN
PspA, -B and -C regulate the bacterial phage shock protein stress response by controlling the PspF transcription factor. Here, we have developed complementary approaches to study the behaviour of these proteins at their endogenous levels in Yersinia enterocolitica. First, we observed GFP-tagged versions with an approach that resolves individual protein complexes in live cells. This revealed that PspA, -B and -C share common behaviours, including a striking contrast before and after induction. In uninduced cells, PspA, -B and -C were highly mobile and widely distributed. However, induction reduced mobility and the proteins became more organized. Combining mCherry- and GFP-tagged proteins also revealed that PspA colocalizes with PspB and PspC into large stationary foci, often located close to the pole of induced cells. In addition, co-immunoprecipitation assays provided the first direct evidence supporting the model that PspA switches binding partners from PspF to PspBC upon induction. Together, these data suggest that PspA, -B and -C do not stably interact and are highly mobile before induction, perhaps sampling the status of the membrane and each other. However, an inducing signal promotes PspABC complex formation and their relocation to discrete parts of the membrane, which might then be important for mitigating envelope stress.
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Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica , Proteínas de Choque Térmico/metabolismo , Estrés Fisiológico , Yersinia enterocolitica/fisiología , Fusión Artificial Génica , Membrana Celular/química , Genes Reporteros , Inmunoprecipitación , Proteínas Luminiscentes/análisis , Proteínas Luminiscentes/genética , Unión Proteica , Mapeo de Interacción de Proteínas , Proteínas Recombinantes de Fusión , Coloración y EtiquetadoRESUMEN
Induced pluripotent stem cells (iPSCs) can be generated from patients with specific diseases by the transduction of reprogramming factors and can be useful as a cell source for cell transplantation therapy for various diseases with impaired organs. However, the low efficiency of iPSC derived from somatic cells (0.01-0.1%) is one of the major problems in the field. The phosphoinositide 3-kinase (PI3K) pathway is thought to be important for self-renewal, proliferation, and maintenance of embryonic stem cells (ESCs), but the contribution of this pathway or its well-known negative regulator, phosphatase, and tensin homolog deleted on chromosome ten (Pten), to somatic cell reprogramming remains largely unknown. Here, we show that activation of the PI3K pathway by the Pten inhibitor, dipotassium bisperoxo(5-hydroxypyridine-2-carboxyl)oxovanadate, improves the efficiency of germline-competent iPSC derivation from mouse somatic cells. This simple method provides a new approach for efficient generation of iPSCs.
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Células Madre Pluripotentes Inducidas/citología , Fosfohidrolasa PTEN/genética , Transducción de Señal/efectos de los fármacos , Animales , Proliferación Celular , Células Cultivadas , Células Madre Embrionarias/citología , Células Madre Embrionarias/metabolismo , Femenino , Vectores Genéticos , Inmunohistoquímica , Cariotipificación , Masculino , Ratones , Ratones Endogámicos ICR , Fosfohidrolasa PTEN/antagonistas & inhibidores , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Regiones Promotoras Genéticas , Retroviridae/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Vanadatos/farmacologíaRESUMEN
BACKGROUND: It is very important to evaluate atherosclerosis at an early stage since cardiovascular disease is the main cause of death in patients with end stage renal disease. The purpose of our study was to examine which of the following parameters of atherosclerosis is the best index for the prediction of cardiovascular death or events in hemodialysis patients: intima media thickness (IMT), ankle-brachial index (ABI) and cardio-ankle vascular index (CAVI), and whether visceral fat area (VFA) and subcutaneous fat area (SFA), also predict those events. METHODS: VFA, SFA, IMT, ABI and CAVI were measured using CT or a dedicated device in 270 hemodialysis patients(age: 63.3 +/- 12.3 years, male 56.3%). RESULTS: During a median follow-up period of 54 months, cardiovascular deaths or events occurred in 92 (34.1%) patients. Seventy (25.9%) patients died, 27 (38.6%) of them due to cardiovascular events. Whereas several baseline clinical covariates showed an associated risk for composite cardiovascular events in a univariate Cox proportional hazards analysis, almost all of them became insignificant when analyzed together. Only age, SFA, and a prevalence of diabetes remained significant in multivariate analysis. When both IMT and ABI were included in this model, all other covariates became insignificant, while ABI, but not IMT, was also related to the prediction of cardiovascular death on top of age and SFA. CONCLUSIONS: Both ABI and IMT were useful predictors for composite cardiovascular events, with ABI being also associated with a risk for cardiovascular deaths. In addition, SFA was a useful predictor for both cardiovascular events and cardiovascular deaths.
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Enfermedades Cardiovasculares/etiología , Fallo Renal Crónico/complicaciones , Anciano , Enfermedades Cardiovasculares/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Diálisis Renal/efectos adversos , Factores de RiesgoRESUMEN
Introduction: Dellen is a corneal disease characterized by shallow, saucer-like excavations at the corneal margin. Herein, we presented a case of dellen formation that developed following a 27-gauge pars plana vitrectomy (PPV) and was rapidly resolved using scleral and conjunctival sutures. Case Presentation: A 73-year-old woman underwent a 27-gauge PPV for the epiretinal membrane of the right eye. Intraoperatively, owing to coexisting diabetic retinopathy, the peripheral vitreous was shaved, and retinal photocoagulation was performed on the peripheral retina. The intraocular pressure (IOP) was 15 mm Hg on 1 day after the PPV and on postoperative day 4; however, on day 14, the IOP decreased to 10 mm Hg, and conjunctival bleb formation was observed. By day 18, the bleb height remained unchanged, and dellen formation was noted at the corneal periphery. Because of marked corneal thinning, conjunctival and scleral sutures were placed 20 days following the PPV. Intraoperative findings revealed leakage from the scleral wound at the trocar puncture site. The IOP increased to 20 mm Hg at 19 h following the suture, resulting in the disappearance of the bleb and dellen. Since then, the bleb or dellen did not recur. Conclusion: We encountered a case of late-onset scleral wound cleavage 2 weeks following microincision vitreous surgery, resulting in bleb and dellen formation, which was immediately managed by the scleral and conjunctiva suturing.
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PURPOSE: We investigated the effects of a warm compress immediately before surgery on the ocular surface and intraoperative visibility during surgery. METHODS: A randomised controlled quasi-experiment at Saitama Medical University Hospital. From November 2020 to September 2021, 200 patients scheduled for endophthalmic surgery were randomly assigned to a group that received a hot compress with a spontaneously heating eye mask (HM group) or a group that received only an eye mask (control group). The eye masks were applied for 20 min from 2 hours before surgery, and before and after mask application in the non-invasive tear break-up time (NIBUT), tear meniscus height (TMH) and obstruction score of the meibomian gland (meiboscore) were evaluated. The time from wetting to dry blurring of the corneal surface (corneal blurring time, CBT) was also compared before and after the warm compress. RESULTS: We enrolled 100 patients in the HM group (mean age 69.0±13.3 years) and 99 patients in the control group (mean age 69.5±16.2 years). In the control group, there were no significant changes in the NIBUT, meiboscore or TMH before and after eye mask use, whereas in the HM group, the NIBUT increased from 6.7±5.1 to 9.5±5.6 s (p<0.001), the meiboscore improved from 0.71±0.93 to 0.63±0.96 (p=0.03) and the TMH significantly improved from 0.22±0.08 to 0.24±0.08 mm (p<0.001). The CBT was longer the HM group than control group (33.5±13.4 s, 25.7±14.9 s, respectively, p=0.01). CONCLUSIONS: The condition of the ocular surface and intraoperative visibility improved after a single warm compress. TRIAL REGISTRATION NUMBER: UMIN R000047286.
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Glándulas Tarsales , Oftalmología , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Córnea , Proyectos de Investigación , CaraRESUMEN
Regulation of the bacterial phage-shock-protein (Psp) system involves communication between integral (PspBC) and peripheral (PspA) cytoplasmic membrane proteins and a soluble transcriptional activator (PspF). In this study protein subcellular localization studies were used to distinguish between spatial models for this putative signal transduction pathway in Yersinia enterocolitica. In non-inducing conditions PspA and PspF were almost exclusively in the soluble fraction, consistent with them forming an inhibitory complex in the cytoplasm. However, upon induction PspA, but not PspF, mainly associated with the membrane fraction. This membrane association was dependent on PspBC but independent of increased PspA concentration. Analysis of psp null, overexpression and altered function mutants further supported a model where PspA is predominantly membrane associated only when the system is induced. Activation of the Psp system normally leads to a large increase in PspA concentration and we found that this provided a second mechanism for its membrane association, which did not require PspBC. These data suggest that basal PspFABC protein levels constitute a regulatory switch that moves some PspA to the membrane when an inducing trigger is encountered. Once this switch is activated PspA concentration increases, which might then allow it to directly contact the membrane for its physiological function.
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Proteínas Bacterianas/metabolismo , Proteínas de Choque Térmico/metabolismo , Proteínas de la Membrana/metabolismo , Transducción de Señal , Yersinia enterocolitica/genética , Proteínas Bacterianas/genética , Regulación Bacteriana de la Expresión Génica , Proteínas de Choque Térmico/genética , Proteínas de la Membrana/genética , Mutación , Yersinia enterocolitica/metabolismoRESUMEN
Objective and Methods: A total of 21 published studies on self-management for people with multiple sclerosis (MS) were reviewed to explore the significance and potential of self-management for people with HTLV-1 associated myelopathy (HAM). These studies were classified based on three concepts: self-management regimen and preferences, context of self-management, and outcomes of self-management. Results: Self-management regimens for people with MS include medical, role, and emotional management. Moreover, self-management regimens are closely associated with the context of self-management, emphasizing the importance of investigating contextual factors and regimens concurrently. Quality of life (QOL) has been evaluated as an outcome of self-management, and self-management has been shown to have both positive and negative effects on the QOL of people with MS. However, insufficient studies focus on self-management regimens and patient preferences; further investigation is necessary to develop effective self-management interventions that reflect the often unique nature of the disease for each individual. The characteristics of HAM are also unique to individual patients. Therefore, investigation of people with HAM in particular is required. Conclusion: This literature review examined the significance of investigating self-management for people with HAM.
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Relatively high circulating levels of soluble tumor necrosis factor (TNF) receptors (TNFRs: TNFR1, TNFR2) have been associated with not only progression to end-stage renal disease but also mortality in patients with diabetes. It remains unknown whether elevated TNFR levels in haemodialysis patients are associated with mortality. We studied 319 patients receiving maintenance haemodialysis who were followed for a median of 53 months. Circulating markers of TNF pathway (TNFα and TNFRs) were measured with immunoassay. Strong positive correlations between TNFR1 and TNFR2 were observed (r = 0.81, P < 0.0001). During follow-up, 88 (27.6%) patients died of any cause (40 [45.5%] died of cardiovascular disease). In the Cox multivariate model, either TNFR but not TNFα remained a significant independent predictor of all-cause mortality (TNFR1: hazard ratio [HR] 2.34, 95% confidence interval [CI], 1.50-3.64; TNFR2: HR 2.13, 95% CI 1.38-3.29) after adjustment for age, prior cardiovascular disease, predialysis systolic blood pressure, and large systolic blood pressure decline during dialysis session. For cardiovascular mortality, significance was only observed in TNFR1 (TNFR1: HR 2.15, 95% CI 1.13-4.10). Elevated TNFRs levels were associated with the risk of cardiovascular and/or all-cause mortality independent of all relevant covariates in patients undergoing haemodialysis.
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Fallo Renal Crónico/sangre , Fallo Renal Crónico/mortalidad , Receptores Tipo II del Factor de Necrosis Tumoral/sangre , Receptores Tipo I de Factores de Necrosis Tumoral/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores , Causas de Muerte , Femenino , Estudios de Seguimiento , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Diálisis Renal , Factores de Tiempo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Ornithine transcarbamylase (OTC) deficiency is the most common inherited disorder of the urea cycle and is transmitted as an X-linked trait. Defects in the OTC gene cause a block in ureagenesis resulting in hyperammonemia, which can lead to brain damage and death. Three previous mutation updates for the OTC gene have been published, in 1993, 1995, and 2002. The most recent comprehensive update, in 2002, contained 244 mutations including 13 nondisease-causing mutations and polymorphisms. This current update reports 341 mutations, of which 93 have not been previously reported, and an additional 29 nondisease-causing mutations and polymorphisms. Out of the 341 mutations, 149 were associated with neonatal onset of hyperammonemia (within the first week of life), 70 were seen in male patients with later onset of hyperammonemia, and 121 were found in heterozygous females (one unknown). Along with the reported mutations, residual enzyme activities and other pertinent clinical information are included whenever available. Most mutations in the OTC gene are specific to a particular family ("private" mutations). They are distributed throughout the gene, with a significant paucity of mutations in the 32 first codons encoding the "leader" peptide (exon 1 and the beginning of exon 2). Almost all mutations in consensus splice sites confer a neonatal onset phenotype. Using the current molecular screening methods, mutations are found in about 80% of the patients. The remaining patients may have mutations in regulatory domains or mutations deep in the introns, which constitute 98.5% of the genomic sequence. In addition, a phenocopy of OTC deficiency caused by mutations in another unknown gene cannot be excluded.
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Mutación Missense , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa/diagnóstico , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa/genética , Ornitina Carbamoiltransferasa/genética , Polimorfismo Genético , Secuencia de Aminoácidos , Femenino , Humanos , Masculino , Datos de Secuencia Molecular , Análisis de Secuencia de ProteínaRESUMEN
Hematopoietic stem/progenitor cells (HSPCs) derived from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have potential therapeutic applications in humans. To assess the safety and efficacy of ESC/iPSC-based therapies, reliable animal models are required prior to their clinical application. The common marmoset (CM) was recently found to be a useful nonhuman primate animal model for drug development and safety assessment. However, a method for the efficient hematopoietic differentiation of CM ESCs has not been established. In this study, we developed a novel and efficient method for differentiating CM ESCs into hematopoietic cells by transiently inhibiting the phosphoinositide 3-kinase (PI3K)-Protein kinase B (AKT) pathway, a critical pathway that maintains the undifferentiated state of CM ESCs during embryoid body (EB) formation. Compared with controls, transient inhibition of the P13K-AKT pathway resulted in a threefold increase in the proportion of enriched CD34⺠cells (p < 0.001) and an increase in the number of hematopoietic colonies on day 8 of CM EB cultures. Moreover, number of blast colonies, number of hematopoietic progenitor cell populations of CD34âºCD117âº, CD34âºCD45âº, and CD43âºCD45⺠cells, and expression of hematopoietic genes were increased by transient inhibition of the PI3K-AKT pathway. We also demonstrated that the hematopoietic progenitor cell population was increased by inhibition of PI3K in a human system. Our novel and efficient ESC differentiation method might be useful for preclinical research on human hematopoietic disorders and may be efficiently translated to human ESC/iPSC-based regenerative medicine.
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Diferenciación Celular/fisiología , Células Madre Embrionarias/metabolismo , Hematopoyesis/fisiología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Antígenos CD/metabolismo , Callithrix , Línea Celular , Células Madre Embrionarias/citología , Humanos , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/metabolismoRESUMEN
OBJECTIVES: The aim of this study was to investigate the effects of sandblasting, etching, and a silane coupling agent on the ability of dual-cured resin cement to bond to glass ceramics designed for in indirect adhesive restoration. METHODS: A cast glass ceramic (Olympus Castable Ceramics) with a crystalline phase consisting of mica and beta-spondumene was selected as the substrate material. The glass surfaces, which were sandblasted, polished, or etched with phosphoric acid or hydrofluoric acid (HF), were bonded with a dual-cured resin cement (Panavia Fluoro Cement) using a dentin adhesive system (Clearfil SE Bond), both with and without a silane coupling agent. A micro-shear bond test was carried out to measure the bond strength of the resin cement to the glass surface. Each glass surface was bonded and tested using the shear test. In addition, surfaces with the bonding removed after the shear bond test, the adhesive interface between the glass and cement, and an etched glass surface without any bonding, were studied morphologically using scanning electron microscopy or field emission scanning electron microscopy. RESULTS: Usage of a silane coupling agent effectively raised the bond-strength values of resin cement (Fisher's PLSD, P<0.01). The effectiveness of using phosphoric acid etching to improve bonding was not clear (Fisher's PLSD, P>0.01). HF-etching for 30s seemed to over-etch the glass surface, resulting in adverse effects on bonding (Fisher's PLSD, P<0.01). SIGNIFICANCE: The micro-shear bond strength between Olympus Castable Ceramics and resin cement can be increased by the silane coupling agent used along with an acidic primer.
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Cerámica , Recubrimiento Dental Adhesivo , Porcelana Dental , Recubrimientos Dentinarios , Cementos de Resina , Grabado Ácido Dental/métodos , Análisis de Varianza , Técnica de Colado Dental , Recubrimientos Dentinarios/química , Ácido Fluorhídrico , Incrustaciones , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Cementos de Resina/química , Silanos , Estadísticas no Paramétricas , Estrés Mecánico , Propiedades de Superficie , Resistencia a la TracciónRESUMEN
PURPOSE: The purpose of this study was to evaluate the in vitro dentin bond strengths of two dentin bonding systems in Class I cavities following fatigue load cycling (FLC) with thermal cycling (TC). MATERIALS AND METHODS: Class I cavities were prepared in 12 human molars and restored with either Clearfil SE Bond (SE) and Clearfil AP-X resin composite (AP-X) or Single Bond (SB)/AP-X according to the manufacturers' instructions. After water storage for 1 week, untreated controls and test samples were subjected to 50,000 FLC with TC from 5 degrees C to 55 degrees C for 625 cycles and stored in water for 1 week. Microtensile bond strength (MTBS) tests were measured on the floor of the cavities at a crosshead speed of 1 mm/min. Data were statistically analyzed using one- and two-way ANOVA and Fisher's PLSD test at a 5% level of significance. RESULTS: The MPa results were: SE 30.5+/-12.8 (control) and 23.2+/-10.8 (50,000 FLC); SB 5.1+/-9.2 (control) and 4.7+/-5.7 (50,000 FLC). Bond strengths were not statistically significantly affected by FLC (p > 0.05); however, they were influenced by the bonding system (p < 0.05). The MTBS of SE was significantly higher than that of SB (p < 0.05) under FLC and TC test conditions. Over half of the SB specimens debonded during sample preparation, showing blister-like structures, suggesting that an over-wet phenomenon occurred on the cavity floor. CONCLUSION: SE produced excellent dentin bonds that were much stronger than those produced by SB, which was shown to be a technique-sensitive bonding system.
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Recubrimiento Dental Adhesivo , Preparación de la Cavidad Dental/clasificación , Recubrimientos Dentinarios/química , Dentina/ultraestructura , Grabado Ácido Dental , Análisis de Varianza , Bisfenol A Glicidil Metacrilato/química , Resinas Compuestas/química , Humanos , Ensayo de Materiales , Metacrilatos/química , Microscopía Electrónica de Rastreo , Diente Molar , Cementos de Resina/química , Estadística como Asunto , Estrés Mecánico , Propiedades de Superficie , Temperatura , Resistencia a la Tracción , Termodinámica , Agua/química , Soporte de PesoRESUMEN
Common marmoset (CM) is widely recognized as a useful non-human primate for disease modeling and preclinical studies. Thus, embryonic stem cells (ESCs) derived from CM have potential as an appropriate cell source to test human regenerative medicine using human ESCs. CM ESCs have been established by us and other groups, and can be cultured in vitro. However, the growth factors and downstream pathways for self-renewal of CM ESCs are largely unknown. In this study, we found that basic fibroblast growth factor (bFGF) rather than leukemia inhibitory factor (LIF) promoted CM ESC self-renewal via the activation of phosphatidylinositol-3-kinase (PI3K)-protein kinase B (AKT) pathway on mouse embryonic fibroblast (MEF) feeders. Moreover, bFGF and transforming growth factor ß (TGFß) signaling pathways cooperatively maintained the undifferentiated state of CM ESCs under feeder-free condition. Our findings may improve the culture techniques of CM ESCs and facilitate their use as a preclinical experimental resource for human regenerative medicine.
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INTRODUCTION AND OBJECTIVE: While pruritus is a common complication in hemodialysis patients, the pathophysiological mechanisms remain obscure. Recently, B-type (brain) natriuretic peptide (BNP) has been defined as an itch-selective neuropeptide in pruriceptive neurons in mice, and higher serum levels of BNP are frequently observed in hemodialysis patients. The objective of the present study was to evaluate the role of serum BNP in pruritus in patients undergoing hemodialysis. PATIENTS AND METHODS: The current cross-sectional study was performed on 43 patients undergoing maintenance hemodialysis. A visual analog scale (VAS) measuring the general severity of pruritus (values from 0 to 10, with higher values indicating more severe pruritus) in daytime and at night was self-reported by patients. Each patient's background and laboratory tests, including serum BNP in the post-hemodialysis period, were collected. The correlation between VAS and clinical parameters was evaluated. RESULTS: Both daytime and nighttime VAS scores in diabetic patients were significantly less than those in nondiabetic patients. Multiple regression analysis revealed that pruritus in daytime was worsened by serum BNP (ß=2.0, t=2.4, P=0.03), calcium (ß=4.4, t=5.2, P<0.0001), and ß2-microglobulin (ß=2.0, t=3.0, P=0.007), while it was eased by age (ß=-2.2, t=-3.2, P=0.0004). Nocturnal pruritus was severe in nondiabetic patients (ß=1.7, t=3.8, P=0.0005) and weakened by the total iron binding capacity (ß=-2.9, t=-3.1, P=0.004). CONCLUSION: It is suggested that a higher level of serum BNP increases the pruritus of hemodialysis patients in daytime and that diabetic patients are less sensitive to itch, especially at nighttime.
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The objectives of the present study are (1) to compare the cardioankle vascular index (CAVI), ankle-brachial index (ABI), and carotid artery intima-media thickness (CA-IMT) between HD patients with and without type 2 diabetes (T2D) or prevalence of cardiovascular (CV) disease and (2) also to evaluate the relationship of these indices with CA-IMT in these patients according to ABI levels. This study consisted of 132 HD patients with T2D and the same number of patients without T2D. The patients with diabetes or prevalence of CV disease had significantly higher CA-IMT and lower ABI values than those without diabetes or prevalence of CV disease, respectively. Although diabetic patients had higher CAVI than those without diabetes, CAVI did not differ between patients with or without prevalence of CV disease. In univariate analysis, CA-IMT was more strongly correlated with ABI than CAVI. However, the opposite was true in patients with an ABI value of more than 0.95. Both indices were significantly correlated with CA-IMT although ABI was a powerful determinant than CAVI. It appears that both indices are associated with CA-IMT in HD patients, especially with an ABI value of more than 0.95.
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The phage shock protein (Psp) system is a conserved extracytoplasmic stress response in bacteria that is essential for virulence of the human pathogen Yersinia enterocolitica. This article summarizes some recent findings about Y. enterocolitica Psp system function. Increased psp gene expression requires the transcription factor PspF, but under non-inducing conditions PspF is inhibited by an interaction with another protein, PspA, in the cytoplasm. A Psp-inducing stimulus causes PspA to relocate to the cytoplasmic membrane, freeing PspF to induce psp gene expression. This PspA relocation requires the integral cytoplasmic membrane proteins, PspB and PspC, which might sense an inducing trigger and sequester PspA by direct interaction. The subsequent induction of psp gene expression increases the PspA concentration, which also allows it to contact the membrane directly, perhaps for its physiological function. Mutational analysis of the PspB and PspC proteins has revealed that they both positively and negatively regulate psp gene expression and has also identified PspC domains associated with each function. We also compare the contrasting physiological roles of the Psp system in the virulence of Y. enterocolitica and Salmonella enterica sv. Typhimurium (S. Typhimurium). In S. Typhimurium, PspA maintains the proton motive force, which provides the energy needed to drive ion importers required for survival within macrophages. In contrast, in the extracellular pathogen Y. enterocolitica, PspB and PspC, but not PspA, are the Psp components needed for virulence. PspBC protect Y. enterocolitica from damage caused by the secretin component of its type 3 secretion system, an essential virulence factor.