RESUMEN
Vancomycin is associated with nephrotoxicity; however, the influence of the number of combined nephrotoxic agents on the incidence of vancomycin nephrotoxicity has not been clarified. We investigated patient backgrounds in 148 inpatients who received vancomycin treatment. The patients were divided into nephrotoxicity (n=35) and non-nephrotoxicity (n=113) groups. A comparison of the patient backgrounds in the two groups revealed significant differences in weight, changes in serum creatinine before vancomycin administration, blood urea nitrogen to serum creatinine ratio, length of vancomycin therapy, vancomycin trough concentration, and number of combined nephrotoxic agents. Multiple logistic regression analysis using these six factors as autonomous variables showed that the highest vancomycin trough concentration (odds ratio, 1.080; 95% confidence interval, 1.030-1.140; p = 0.003) and the number of combined nephrotoxic agents (odds ratio, 1.590; 95% confidence interval, 1.120-2.260; p = 0.010) were significantly related to nephrotoxicity.
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Antibacterianos/efectos adversos , Enfermedades Renales/inducido químicamente , Vancomicina/efectos adversos , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Vancomicina/administración & dosificación , Vancomicina/farmacocinéticaRESUMEN
OBJECTIVES: The potential additive effect of an enamel matrix derivative (EMD) to a subepithelial connective tissue graft (CTG) for recession coverage is still controversially discussed. Therefore, the aim of this study was to histologically evaluate the healing of gingival recessions treated with coronally advanced flap (CAF) and CTG with or without EMD in dogs. MATERIALS AND METHODS: Gingival recession defects (5 mm wide and 7 mm deep) were surgically created on the labial side of bilateral maxillary canines in 7 dogs. After 8 weeks of plaque accumulation and subsequent 2 weeks of chemical plaque control, the 14 chronic defects were randomized to receive either CAF with CTG (CAF/CTG) or CAF with CTG and EMD (CAF/CTG/EMD). The animals were sacrificed 10 weeks after reconstructive surgery for histologic evaluation. RESULTS: Treatment with CAF/CTG/EMD demonstrated statistically significantly better results in terms of probing pocket depth reduction (P < 0.05) and clinical attachment level gain (P < 0.001). The length of the epithelium was statistically significantly shorter in the CAF/CTG/EMD group than in the CAF/CTG group (1.00 ± 0.75 mm vs. 2.38 ± 1.48 mm, respectively, P < 0.01). Cementum formation was statistically significantly greater in the CAF/CTG/EMD group than following treatment with the CAF/CTG group (3.20 ± 0.89 mm vs. 1.88 ± 1.58 mm, respectively, P < 0.01). The CAF/CTG/EMD group showed statistically significantly greater complete periodontal regeneration (i.e., new cementum, new periodontal ligament, and new bone) than treatment with CAF/CTG (0.54 ± 0.73 mm vs. 0.07 ± 0.27 mm, respectively, P < 0.05). CONCLUSION: Within their limits, the present findings indicate that the additional use of EMD in conjunction with CAF + CTG favors periodontal regeneration in gingival recession defects. CLINICAL RELEVANCE: The present findings support the use of EMD combined with CTG and CAF for promoting periodontal regeneration in isolated gingival recession defects.
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Tejido Conectivo , Proteínas del Esmalte Dental , Recesión Gingival , Animales , Tejido Conectivo/trasplante , Perros , Encía , Recesión Gingival/cirugía , Gingivoplastia , Raíz del Diente , Resultado del TratamientoRESUMEN
LAMB1 gene analysis should be considered for intellectually disabled patients with cerebellar cysts, white matter signal change, and cortical malformation. Muscular involvement is absent, in contrast to the α-dystroglycanopathy types of congenital muscular dystrophies.
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Enfermedades Cerebelosas/diagnóstico por imagen , Enfermedades Cerebelosas/genética , Corteza Cerebral/patología , Quistes/diagnóstico por imagen , Quistes/genética , Laminina/genética , Fenotipo , Sustancia Blanca/patología , Adolescente , Niño , Femenino , Humanos , MasculinoRESUMEN
The mitochondrial phosphate carrier gene (PiC) encodes a membrane protein that mediates the supply of inorganic phosphate from the cytosol into the mitochondrial matrix. This substrate-specific transport system plays an important role in efficient ATP synthesis. Mammals appear to have only one PiC with two alternative splicing variants whose functional differences remain unclear. The present study is the first to characterize the multiple genes that encode PiC in insects. Bombyx mori was found to have two PiC paralogues, one ubiquitous and one testis-specific, the latter seeming to be present only in Lepidoptera. Drosophila melanogaster was found to harbour two PiC paralogues, whereas Liriomyza chinensis, another dipteran, has three PiC paralogues. Two PiCs were found to be present in Plautia stali, and silencing either of these genes affected the normal development of P. stali nymphs, although their expression patterns differed amongst tissues. Schistocerca gregaria and Locusta migratoria have two PiC each, with different expression patterns. Tribolium castaneum was found to have only one PiC, which appears to play an essential role in larval development. Thus, although the inorganic phosphate transport system appears to be conserved across eukaryotes, PiC has become specialized in the different tissues of different insect species.
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Proteínas de Insectos/metabolismo , Insectos/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas de Transporte de Fosfato/metabolismo , Animales , Femenino , Proteínas de Insectos/genética , Insectos/genética , Masculino , Proteínas Mitocondriales/genética , Músculos/metabolismo , Proteínas de Transporte de Fosfato/genética , FilogeniaRESUMEN
OBJECTIVE: This study aimed to evaluate the effects of a porcine acellular dermal matrix (PADM) with or without an enamel matrix derivative (EMD) on gingival recession defects treated with a coronally advanced flap (CAF) in dogs. MATERIALS AND METHODS: Miller class II gingival recession defects (5 mm wide and 7 mm deep) were surgically created on the labial side of bilateral maxillary canines in 12 dogs. After 8 weeks of plaque accumulation, the 24 chronic defects were randomly assigned to one of the following 4 treatments: CAF, CAF with PADM (CAF/PADM), CAF with EMD (CAF/EMD), and CAF with EMD and PADM (CAF/EMD/PADM). The animals were sacrificed 10 weeks after surgery for histologic evaluation. RESULTS: In all groups, root coverage was obtained to a varying degree. PADM was well incorporated in gingival connective tissue in the CAF/PADM and in the CAF/EMD/PADM groups. The height of newly formed bone was significantly greater in the CAF/EMD/PADM group than in the CAF and CAF/PADM groups. New cementum with periodontal ligament-like tissue was predominantly found in the CAF/EMD and CAF/EMD/PADM groups. The CAF/EMD/PADM group showed the greatest amount of new cementum among the groups examined, although the difference was not statistically significant. CONCLUSION: Within the limitations of the present study, it can be concluded that CAF/EMD/PADM treatment may promote periodontal regeneration in gingival recession defects. CLINICAL RELEVANCE: The present results suggest that the combination of EMD and PADM in conjunction with CAF may represent a promising approach for treating single Miller class II gingival recessions.
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Dermis Acelular , Proteínas del Esmalte Dental/farmacología , Recesión Gingival/tratamiento farmacológico , Recesión Gingival/cirugía , Colgajos Quirúrgicos , Cicatrización de Heridas/fisiología , Animales , Terapia Combinada , Perros , Gingivoplastia/métodos , Regeneración , PorcinosRESUMEN
OBJECTIVE: Glycosphingolipids (GSLs) are ubiquitous membrane components that play a functional role in maintaining chondrocyte homeostasis. We investigated the potential role of gangliosides, one of the major components of GSLs, in osteoarthritis (OA) pathogenesis. DESIGN: Both age-associated and instability-induced OA models were generated using GM3 synthase knockout (GM3S(-/-)) mice. A cartilage degradation model and transiently GM3S-transfected chondrocytes were analyzed to evaluate the function of gangliosides in OA development. The amount of each series of GSLs in chondrocytes after IL-1α stimulation was profiled using mass spectrometry (MS). RESULTS: OA changes in GM3S(-/-) mice were dramatically enhanced with aging compared to those in wild-type (WT) mice. GM3S(-/-) mice showed more severe instability-induced pathologic OA in vivo. Ganglioside deficiency also led to the induction of matrix metalloproteinase (MMP)-13 and ADAMTS-5 secretion and chondrocyte apoptosis in vitro. In contrast, transient GM3S transfection of chondrocytes suppressed MMP-13 and ADAMTS-5 expression after interleukin (IL)-1α stimulation. GSL profiling revealed the presence of abundant gangliosides in chondrocytes after IL-1α stimulation. CONCLUSION: Gangliosides play a critical role in OA pathogenesis by regulating the expression of MMP-13 and ADAMTS-5 and chondrocyte apoptosis. Based on the obtained results, we propose that gangliosides are potential target molecules for the development of novel OA treatments.
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Artritis Experimental/metabolismo , Cartílago Articular/patología , Gangliósidos/deficiencia , Osteoartritis/metabolismo , Proteínas ADAM/genética , Proteínas ADAM/metabolismo , Proteína ADAMTS5 , Envejecimiento/patología , Animales , Apoptosis/fisiología , Artritis Experimental/patología , Cartílago Articular/efectos de los fármacos , Células Cultivadas , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Condrocitos/patología , Progresión de la Enfermedad , Gangliósidos/fisiología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Interleucina-1alfa/farmacología , Masculino , Metaloproteinasa 3 de la Matriz/genética , Metaloproteinasa 3 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Osteoartritis/patología , Técnicas de Cultivo de TejidosRESUMEN
The ligamentum capitis femoris (LCF) has increased in clinical significance through the development of hip arthroscopy. The histological pathologies and molecular composition of the femoral attachment of the LCF and the degeneration caused by LCF disruption were investigated in the human hip joint. Twenty-four LCFs were retrieved at surgery for femoral neck fracture (age range: 63-87 years). In the "intact" (i.e., intact throughout its length, n = 12) group, the attachment consisted of rich fibrocartilage. Fibrocartilage cells were present in the midsubstance. In contrast, the construction of the attachment in the "disrupted" (i.e., ligament no longer attached to the femoral head, n = 12) group had disappeared. The attachment in the disrupted group was not labeled for type II collagen or aggrecan, while that in the intact group was labeled for types I, II and III collagen, chondroitin 4-sulfate, chondroitin 6-sulfate, aggrecan, and versican. The percentage of single-stranded DNA-positive chondrocytes was significantly higher in the disrupted group than in the intact group. We conclude that the femoral attachment of the LCF has a characteristic fibrocartilaginous structure that is likely to adjust to the mechanical load, and suggest that its degeneration is advanced by disruption and should be regarded as a clinical pathology.
Asunto(s)
Cabeza Femoral/patología , Ligamento Redondo del Fémur/patología , Anciano , Anciano de 80 o más Años , Agrecanos/análisis , Condrocitos/química , Sulfatos de Condroitina/análisis , Colágeno Tipo I/análisis , Colágeno Tipo II/análisis , Colágeno Tipo III/análisis , ADN de Cadena Simple/análisis , Femenino , Fracturas del Cuello Femoral/cirugía , Cabeza Femoral/química , Cabeza Femoral/lesiones , Fibrocartílago/química , Fibrocartílago/patología , Articulación de la Cadera , Humanos , Masculino , Persona de Mediana Edad , Ligamento Redondo del Fémur/química , Ligamento Redondo del Fémur/lesionesRESUMEN
BACKGROUND AND OBJECTIVE: Resistin is an adipocytokine that induces insulin resistance and is predominantly expressed in adipocytes and peripheral blood mononuclear cells. Resistin expression increases in inflammatory diseases as well as diabetes mellitus, and is upregulated by bacterial pathogens and proinflammatory cytokines. The aim of this study was to identify resistin in human gingival crevicular fluid, to compare the resistin levels in gingival crevicular fluid between subjects with and without periodontitis and diabetes mellitus and to investigate the regulation of resistin release from human neutrophils by Porphyromonas gingivalis lipopolysaccharide (P-LPS). MATERIAL AND METHODS: Gingival crevicular fluid samples were collected from patients with chronic periodontitis (n = 24), patients with diabetes mellitus-related periodontitis (n = 18) and healthy subjects (n = 21). Resistin in gingival crevicular fluid was determined using western blot analysis and an ELISA kit. The glycated hemoglobin (HbA(1c)) value was obtained from patients with diabetes mellitus-related periodontitis by a medical interview. Human neutrophils were cultured with P-LPS (0-1000 ng/mL), or incubated with inhibitors of actin or microtubule polymerization in the absence or presence of P-LPS. The medium and cellular fractions were used for determination of resistin by ELISA. RESULTS: The resistin level in gingival crevicular fluid from patients with periodontitis or diabetes mellitus-related periodontitis was significantly higher than that of healthy subjects. The resistin level in gingival crevicular fluid was correlated with gingival index score, but not blood HbA(1c) value. The P-LPS increased resistin release from human neutrophils, and its induction was decreased by actin polymerization inhibitors. CONCLUSION: We show, for the first time, the presence of resistin in gingival crevicular fluid. A high resistin level in gingival crevicular fluid samples from periodontitis patients may to some extent be related to P-LPS-induced resistin release from neutrophils.
Asunto(s)
Líquido del Surco Gingival/química , Lipopolisacáridos/farmacología , Neutrófilos/efectos de los fármacos , Porphyromonas gingivalis , Resistina/análisis , Proteínas de Capping de la Actina/farmacología , Adulto , Anciano , Técnicas de Cultivo de Célula , Periodontitis Crónica/sangre , Periodontitis Crónica/metabolismo , Colchicina/farmacología , Citocalasina B/farmacología , Citocalasina D/farmacología , Complicaciones de la Diabetes/sangre , Complicaciones de la Diabetes/metabolismo , Femenino , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Neutrófilos/metabolismo , Nocodazol/farmacología , Inhibidores de la Síntesis del Ácido Nucleico/farmacología , Índice Periodontal , Bolsa Periodontal/sangre , Bolsa Periodontal/metabolismo , Periodontitis/sangre , Periodontitis/metabolismo , Resistina/metabolismo , Moduladores de Tubulina/farmacologíaRESUMEN
BACKGROUND AND OBJECTIVE: Gingival crevicular fluid is a bodily fluid transuded from periodontal tissues into the gingival crevice and periodontal pocket, and contains many species of components. Proteins in gingival crevicular fluid have been studied as markers for periodontal diseases. Mass spectrometric analysis is used for the analyses of proteins, lipids, saccharides and metals, and expected as an approach for disease diagnosis. For better analysis of the protein components in gingival crevicular fluid, we investigated proteins in gingival crevicular fluid samples from the healthy gingival crevice and periodontal pocket using mass spectrometry. MATERIAL AND METHODS: Gingival crevicular fluid samples were collected from subjects who gave their informed consent and were periodontally healthy or had diseased pockets. These samples were electrophoretically separated, and each fraction on the gels was analysed by nano liquid chromatography coupled with tandem mass spectrometry. Antimicrobial peptides detected in gingival crevicular fluid were confirmed by western blotting. RESULTS: One hundred and four proteins were detected in gingival crevicular fluid samples from both healthy sites and sites of periodontitis; 64 proteins were contained only in gingival crevicular fluid from healthy sites and 63 proteins were observed only in gingival crevicular fluid from periodontitis sites. These proteins were blood-, cytoskeleton-, immunity-, inflammation- and lipid-related proteins and enzymes. Some proteins, including ceruloplasmin, glycogen phosphorylase, glutathione S-transferase, phosphoglycerate mutase, psoriasin, S100A11 and resistin, were identified for the first time in gingival crevicular fluid. Antimicrobial peptides, such as lactoferrin, α1-antitrypsin, lipocalin, S100A7, S100A8, S100A9 and cathelicidin, were observed by mass spectrometry and western blotting. CONCLUSION: Multiple protein components in gingival crevicular fluid were analysed at the same time using mass spectrometry, and this approach may be useful for the diagnosis of periodontal diseases.
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Péptidos Catiónicos Antimicrobianos/análisis , Líquido del Surco Gingival/química , Bolsa Periodontal/metabolismo , Periodontitis/diagnóstico , Proteínas/análisis , Espectrometría de Masas en Tándem/métodos , Adulto , Anciano , Western Blotting , Estudios de Casos y Controles , Ceruloplasmina/análisis , Cromatografía Liquida , Electroforesis en Gel de Poliacrilamida , Femenino , Líquido del Surco Gingival/enzimología , Glutatión Transferasa/análisis , Glucógeno Fosforilasa/análisis , Humanos , Masculino , Persona de Mediana Edad , Bolsa Periodontal/enzimología , Fosfoglicerato Mutasa/análisis , Resistina/análisis , Proteína A7 de Unión a Calcio de la Familia S100 , Proteínas S100/análisisRESUMEN
The time-dependent density functional theory (TDDFT) is the leading computationally feasible theory to treat excitations by strong electromagnetic fields. Here the theory is applied to coherent optical phonon generation produced by intense laser pulses. We examine the process in the crystalline semimetal antimony (Sb), where nonadiabatic coupling is very important. This material is of particular interest because it exhibits strong phonon coupling and optical phonons of different symmetries can be observed. The TDDFT is able to account for a number of qualitative features of the observed coherent phonons, despite its unsatisfactory performance on reproducing the observed dielectric functions of Sb. A simple dielectric model for nonadiabatic coherent phonon generation is also examined and compared with the TDDFT calculations.
RESUMEN
We analyzed the immunohistochemical labeling patterns of the extracellular matrix of the coracoclavicular ligaments (CCL) in order to relate the molecular composition of the attachment sites to their mechanical environment. Ligaments were exposed from 12 fresh-frozen human cadaveric samples (four males, mean age: 48.6 ± 12.1 years). Cryosection of methanol-fixed and decalcified tissue was cut and sections were labeled with a panel of monoclonal antibodies directed against collagens, proteoglycans and proteins of vascular components. Attachment sites of both ligaments showed characteristic fibrocartilaginous labeling of collagen type II, aggrecan and link protein in all samples. Labeling for type II collagen was most conspicuous at the insertion of the coracoid process. Morphometry of adjacent samples revealed a fibrocartilage zone of 10-15% in relationship with the ligament proper, where labeling for type II collagen, aggrecan and link protein was negative. The presence of fibrocartilage at both entheses of the trapezoid and conoid ligament suggests that the CCL complex is subject to shear/compression forces. A variable fibrocartilage differentiation at the entheses of both ligaments may be related to the marked change in loading and insertion angle that the ligaments undergo during shoulder movement.
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Matriz Extracelular/química , Ligamentos/anatomía & histología , Ligamentos/química , Adulto , Agrecanos/análisis , Fenómenos Biomecánicos/fisiología , Cadáver , Clavícula , Colágeno Tipo II/análisis , Proteínas de la Matriz Extracelular/análisis , Femenino , Fibrocartílago/anatomía & histología , Fibrocartílago/química , Humanos , Inmunohistoquímica , Ligamentos/irrigación sanguínea , Masculino , Persona de Mediana Edad , Proteoglicanos/análisis , Escápula , Hombro/irrigación sanguínea , Hombro/fisiologíaRESUMEN
BACKGROUND: The time to return to sport from acute hamstring strain injuries is associated with several functional and structural impairments. However, not all previous studies assessed the preinjury level before acute hamstring strain injuries directly. The purpose of this study was to examine the associations of the time to return to performance following acute hamstring strain injuries with deficits in running biomechanics, hamstring function and structure in collegiate sprinters by a prospective study. METHODS: Using a prospective cohort design, 72 participants were recruited from a collegiate track and field team. At the preinjury assessment, a 60-m running-specific test, passive straight leg raise test and isometric knee flexion strength test were assessed at the beginning of the competitive season for three consecutive years (2017-2019). Afterwards, postinjury examinations were performed only in sprinters with acute hamstring strain injuries. FINDINGS: Twelve sprinters strained their hamstring muscle (incidence rate of hamstring strain injuries: 16.7%); the majority (n = 10) were classified as grades 0-2. The running speed deficit of the running-specific test was associated with the time to return to performance as well as the passive straight leg raise test deficit. In the running-specific test, lower-limb kinetic deficits were more strongly associated with the time to return to performance compared to lower-limb kinematic deficits. INTERPRETATION: A running-specific test may be considered one of the most convenient and valid tests for assessing rehabilitation progress after acute hamstring strain injuries.
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Músculos Isquiosurales , Deportes , Humanos , Estudios ProspectivosRESUMEN
Pegylated interferon and ribavirin combination therapy is the standard treatment for patients with chronic hepatitis C (CHC). Some groups have reported a relation between lipid values and response while others have reported that microsomal triglyceride transfer protein, a key enzyme in the assembly and secretion of lipoproteins, was related to hepatitis C virus (HCV). The aim of this study was to investigate the association between the lipoprotein profiles, classified according to size, and hepatitis C treatment and the usefulness for predicting the outcome of treatment. Forty-four patients with CHC (27 men and 17 women) were included in the study. The serum cholesterol and triglyceride (TG) levels in the lipoprotein subclasses were determined using high-performance liquid chromatography with gel permeation columns, which classified lipoproteins into 20 subfractions based on particle size. According to a univariate analysis, those who achieved an sustained viral response (SVR) had a significantly higher serum total cholesterol level, higher cholesterol levels in the low-density lipoprotein subfraction (25.5 nm in diameter) and the very low-density lipoprotein (VLDL) subfraction (44.5 and 36.8 nm), and a higher serum TG level in the VLDL subfraction (44.5 nm), compared with the corresponding values in the non-SVR group. Higher serum cholesterol and TG concentrations in the lipoprotein subfractions were predictive of an SVR to therapy for HCV infection with genotype 1b prior to the start of interferon treatment.
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Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Lipoproteínas/sangre , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Anciano , Pueblo Asiatico , Colesterol/sangre , Femenino , Genotipo , Hepacivirus/clasificación , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C/diagnóstico , Hepatitis C/virología , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Proteínas Recombinantes , Resultado del Tratamiento , Triglicéridos/sangreRESUMEN
Pegylated interferon and ribavirin combination therapy is the standard treatment for patients with chronic hepatitis C (CHC), but treatment failure can be difficult to predict. We and others have reported a relation between lipid values and sustained viral responses in patients with CHC. However, the relationship between lipid values and treatment failure has not been previously reported. The present study investigated the association between the profiles of phospholipids and free cholesterol (FC), the main constitutive ingredients of the surface of lipoprotein, classified according to particle size and hepatitis C treatment, and determined the usefulness of these parameters for predicting the outcome of treatment. Fifty-five patients with CHC (33 men and 22 women) were included in the study. The serum total cholesterol, triglyceride, phospholipids, and FC levels in the lipoprotein subclasses were determined using high-performance liquid chromatography with gel permeation columns, enabling the lipoproteins to be classified into 13 subclasses according to particle size. According to a univariate analysis, the treatment failure group had a significantly higher serum phospholipid level overall in the high-density lipoprotein (HDL) and medium HDL fractions as well as a higher serum FC level in the HDL fraction and all HDL subclass fractions compared with the corresponding values in the non-nonvirological response group. Higher serum phospholipid and FC concentrations in the HDL subclasses were predictive of a failure to respond in patients with genotype 1b.
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Colesterol/análisis , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Lipoproteínas HDL/química , Fosfolípidos/análisis , Adulto , Anciano , Antivirales/administración & dosificación , Antivirales/uso terapéutico , Cromatografía Líquida de Alta Presión , Femenino , Genotipo , Hepacivirus/efectos de los fármacos , Hepatitis C/virología , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Interferón-alfa/uso terapéutico , Japón , Masculino , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Polietilenglicoles/uso terapéutico , Valor Predictivo de las Pruebas , Proteínas Recombinantes , Ribavirina/administración & dosificación , Ribavirina/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVE: Oral epithelial cells help to prevent against bacterial infection in the oral cavity by producing antimicrobial peptides (AMPs). A broad-spectrum AMP, calprotectin (a complex of S100A8 and S100A9 proteins), is expressed by oral epithelial cells and is up-regulated by interleukin-1alpha (IL-1alpha). Shosaikoto (SST) is a traditional Japanese herbal medicine that has immunomodulatory effects and is reported to enhance the levels of IL-1alpha in epithelial cells. The purpose of this study was to investigate the effect of SST on the expression of calprotectin and other AMPs through the regulation of IL-1alpha in oral epithelial cells. MATERIAL AND METHODS: Human oral epithelial cells (TR146) were cultured with SST (at concentrations ranging from 10 to 250 microg/mL) in the presence or absence of anti-IL-1alpha or IL-1 receptor antagonist. The expression of S100A8- and S100A9-specific mRNAs was examined by northern blotting. Calprotectin expression and IL-1alpha secretion were investigated by immunofluorescent staining or ELISA. The expression of other AMPs and IL-1alpha was analyzed by RT-PCR and by quantitative real-time PCR. RESULTS: Shosaikoto (25 microg/mL) significantly increased the expression of S100A8- and S100A9-specific mRNAs and calprotectin protein. Shosaikoto increased S100A7 expression, but had no effect on the expression of other AMPs. The expression of IL-1alpha-specific mRNA and its protein were slightly increased by SST. A neutralizing antibody against IL-1alpha or IL-1 receptor antagonist inhibited SST up-regulated S100A8/S100A9 mRNA expression. CONCLUSION: These results suggest that SST increases the expression of calprotectin and S100A7 in oral epithelial cells. In response to SST, up-regulation of calprotectin may be partially induced via IL-1alpha.
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Medicamentos Herbarios Chinos/farmacología , Factores Inmunológicos/farmacología , Complejo de Antígeno L1 de Leucocito/efectos de los fármacos , Mucosa Bucal/efectos de los fármacos , Péptidos Catiónicos Antimicrobianos/análisis , Péptidos Catiónicos Antimicrobianos/efectos de los fármacos , Northern Blotting , Calgranulina A/análisis , Calgranulina A/efectos de los fármacos , Calgranulina B/análisis , Calgranulina B/efectos de los fármacos , Línea Celular Tumoral , Células Cultivadas , Medicamentos Herbarios Chinos/administración & dosificación , Células Epiteliales/efectos de los fármacos , Humanos , Factores Inmunológicos/administración & dosificación , Interleucina-1alfa/antagonistas & inhibidores , Interleucina-1alfa/farmacología , Complejo de Antígeno L1 de Leucocito/análisis , Mucosa Bucal/citología , Reacción en Cadena de la Polimerasa/métodos , ARN Mensajero/análisis , ARN Mensajero/efectos de los fármacos , Receptores Tipo I de Interleucina-1/antagonistas & inhibidores , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Through direct interaction with the voltage-dependent anion channel (VDAC), proapoptotic members of the Bcl-2 family such as Bax and Bak induce apoptogenic cytochrome c release in isolated mitochondria, whereas BH3-only proteins such as Bid and Bik do not directly target the VDAC to induce cytochrome c release. To investigate the biological significance of the VDAC for apoptosis in mammalian cells, we produced two kinds of anti-VDAC antibodies that inhibited VDAC activity. In isolated mitochondria, these antibodies prevented Bax-induced cytochrome c release and loss of the mitochondrial membrane potential (Deltapsi), but not Bid-induced cytochrome c release. When microinjected into cells, these anti-VDAC antibodies, but not control antibodies, also prevented Bax-induced cytochrome c release and apoptosis, whereas the antibodies did not prevent Bid-induced apoptosis, indicating that the VDAC is essential for Bax-induced, but not Bid-induced, apoptogenic mitochondrial changes and apoptotic cell death. In addition, microinjection of these anti-VDAC antibodies significantly inhibited etoposide-, paclitaxel-, and staurosporine-induced apoptosis. Furthermore, we used these antibodies to show that Bax- and Bak-induced lysis of red blood cells was also mediated by the VDAC on plasma membrane. Taken together, our data provide evidence that the VDAC plays an essential role in apoptogenic cytochrome c release and apoptosis in mammalian cells.
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Apoptosis/fisiología , Canales Iónicos/fisiología , Mitocondrias Hepáticas/fisiología , Mitocondrias/fisiología , Porinas/fisiología , Secuencia de Aminoácidos , Animales , Anticuerpos/farmacología , Anticuerpos Monoclonales/farmacología , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis , Proteína Proapoptótica que Interacciona Mediante Dominios BH3 , Proteínas Portadoras/metabolismo , Grupo Citocromo c/metabolismo , Eritrocitos/fisiología , Etopósido/farmacología , Células HeLa , Humanos , Mamíferos , Proteínas de la Membrana/metabolismo , Proteínas Mitocondriales , Datos de Secuencia Molecular , Paclitaxel/farmacología , Porinas/química , Conformación Proteica , Proteínas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Endogámicas , Proteínas Recombinantes/metabolismo , Estaurosporina/farmacología , Transfección , Canales Aniónicos Dependientes del Voltaje , Proteína Destructora del Antagonista Homólogo bcl-2 , Proteína X Asociada a bcl-2RESUMEN
We showed in a previous study that odontogenic epithelial cells can be selectively cultured from the enamel organ in serum-free medium and expanded using feeder layers of 3T3-J2 cells. The subcultured odontogenic epithelial cells retain the capacity for ameloblast-related gene expression, as shown by semiquantitative RT-PCR. The purpose of the present study was to evaluate the potential of subcultured odontogenic epithelial cells to form tooth structures in cell-polymer constructs maintained in vivo. Enamel organs from 6-month-old porcine third molars were dissociated into single odontogenic epithelial cells and subcultured on feeder layers of 3T3-J2 cells. Amelogenin expression was detected in the subcultured odontogenic epithelial cells by immunostaining and Western blotting. The subcultured odontogenic epithelial cells were seeded onto collagen sponge scaffolds in combination with fresh dental mesenchymal cells, and transplanted into athymic rats. After 4 weeks, enamel-dentin-like complex structures were present in the implanted constructs. These results show that our culture system produced differentiating ameloblast-like cells that were able to secrete amelogenin proteins and form enamel-like tissues in vivo. This application of the subculturing technique provides a foundation for further tooth-tissue engineering and for improving our understanding of ameloblast biology.
Asunto(s)
Esmalte Dental/fisiología , Dentina/fisiología , Células Epiteliales/citología , Células Madre Mesenquimatosas/citología , Ingeniería de Tejidos/métodos , Ameloblastos/química , Amelogenina/genética , Amelogenina/metabolismo , Animales , Western Blotting , Diferenciación Celular , Esmalte Dental/citología , Esmalte Dental/metabolismo , Dentina/citología , Dentina/metabolismo , Células Epiteliales/metabolismo , Células Epiteliales/trasplante , Expresión Génica , Inmunohistoquímica , Células Madre Mesenquimatosas/metabolismo , Ratones , Microscopía de Contraste de Fase , Células 3T3 NIH , Odontogénesis/fisiología , Ratas , Ratas Desnudas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , PorcinosRESUMEN
Bone augmentation via tissue engineering has generated significant interest. We hypothesized that periosteum-derived cells could be used in place of bone marrow stromal cells (which are widely used) in bone engineering, but the differences in osteogenic potential between these 2 cell types are unclear. Here, we compared the osteogenic potential of these cells, and investigated the optimal osteoinductive conditions for periosteum-derived cells. Both cell types were induced, via bFGF and BMP-2, to differentiate into osteoblasts. Periosteal cells proliferated faster than marrow stromal cells, and osteogenic markers indicated that bone marrow stromal cells were more osteogenic than periosteal cells. However, pre-treatment with bFGF made periosteal cells more sensitive to BMP-2 and more osteogenic. Transplants of periosteal cells treated with BMP-2 after pre-treatment with bFGF formed more new bone than did marrow stromal cells. Analysis of these data suggests that combined treatment with bFGF and BMP-2 can make periosteum a highly useful source of bone regeneration.
Asunto(s)
Huesos/fisiología , Osteogénesis/fisiología , Periostio/citología , Ingeniería de Tejidos/métodos , Adolescente , Adulto , Fosfatasa Alcalina/análisis , Animales , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/fisiología , Trasplante de Médula Ósea , Proteína Morfogenética Ósea 2 , Proteínas Morfogenéticas Óseas/farmacología , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Trasplante de Células , Femenino , Factor 2 de Crecimiento de Fibroblastos/farmacología , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos , Ratones Desnudos , Osteoblastos/efectos de los fármacos , Periostio/efectos de los fármacos , Periostio/fisiología , Células del Estroma/efectos de los fármacos , Células del Estroma/fisiología , Factor de Crecimiento Transformador beta/farmacologíaRESUMEN
Two-dimensional pattern reverse Monte Carlo (2D pattern RMC) analysis is performed to model the structures of nano-particles in uniaxially elongated rubbers using two-dimensional patterns of structure factor of the nano-particles obtained by time-resolved two-dimensional ultra-small angle x-ray scattering. Four spot patterns are observed for a large elongation ratio and the shapes change with increasing elongation ratio. We performed the 2D pattern RMC method for the uniaxial system in order to make a model of the structures from the two-dimensional structure factors. The preliminary results of the 2D pattern RMC analysis of the two-dimensional structure factors of silica particles in a uniaxially elongated styrene-butadiene rubber are presented.
RESUMEN
BACKGROUND AND PURPOSE: Branch atheromatous disease is a stroke subtype considered a risk factor for early neurologic deterioration. Meanwhile, crossed cerebellar diaschisis is thought to be influenced by the degree and location of supratentorial perfusion abnormalities and is associated with the clinical outcome in the case of an ischemic stroke. In this article, our aim was to clarify the utility of using a whole-brain 3D pulsed continuous arterial spin-labeling method as an imaging biomarker for predicting neurologic severity in branch atheromatous disease. MATERIALS AND METHODS: Twenty-three patients with branch atheromatous disease in the lenticulostriate artery territory were enrolled. All patients underwent MR imaging, including DWI, 3D-TOF-MRA, and 3D-arterial spin-labeling. We measured the asymmetry index of CBF in the affected area (branch atheromatous disease), the asymmetry index of the contralateral cerebellar hemisphere (crossed cerebellar diaschisis), and the DWI infarct volume in the lenticulostriate artery territory. We also compared each parameter with the initial NIHSS score with the Pearson correlation coefficient. RESULTS: Among the 23 patients, we found no correlation between NIHSS score and the asymmetry index of CBF in the affected area (branch atheromatous disease) (r = -0.027, P = .724), whereas the asymmetry index of the contralateral cerebellar hemisphere (crossed cerebellar diaschisis) and DWI infarct volumes were significantly correlated with NIHSS score (r = 0.515, P = .012; r = 0.664, P = .001, respectively). CONCLUSIONS: In patients with branch atheromatous disease, 3D-arterial spin-labeling can detect crossed cerebellar diaschisis, which is correlated with the degree of neurologic severity.