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OBJECTIVE: To verify whether ridge preservation is effective in the reduction of dimensional loss and in bone formation compared to spontaneous healing in extraction sockets of periodontally compromised teeth. METHODS: Twenty-six subjects requiring tooth extraction for stage III/IV periodontitis were randomly assigned to one of two interventions: alveolar ridge preservation using collagenated bovine bone mineral and a resorbable collagen membrane (test, RP) or spontaneous healing (control, SH). Six months later, postoperative cone-beam computed tomography (CBCT) was performed to measure the linear and volumetric changes of the sockets compared to baseline scans. Biopsies were retrieved at the implant site for histomorphometric calculations. Nonparametric tests were applied for statistical analysis. RESULTS: Significantly less shrinkage occurred in RP compared to SH, mainly in the crestal zone. The width loss difference between groups was 3.3 mm and 2.2 mm at 1 mm and 3 mm below the crest, respectively (p < .05). RP yielded a gain in socket height of 0.25 mm, whereas a loss of -0.39 mm was observed in SH (p < .05). The percentage of volume loss recorded in RP was also less than that recorded in SH (-26.53% vs -50.34, p < .05). Significantly less bone proportion was detected in biopsies from RP (30.1%) compared with SH (53.9%). A positive association between baseline bone loss and ridge shrinkage was found in SH but not in RP. CONCLUSION: Ridge preservation in extraction sockets of periodontally compromised teeth was effective in reducing the amount of ridge resorption.
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Pérdida de Hueso Alveolar , Aumento de la Cresta Alveolar , Animales , Bovinos , Pérdida de Hueso Alveolar/diagnóstico por imagen , Pérdida de Hueso Alveolar/cirugía , Proceso Alveolar/diagnóstico por imagen , Proceso Alveolar/cirugía , Extracción Dental , Alveolo Dental/diagnóstico por imagen , Alveolo Dental/cirugía , HumanosRESUMEN
Senescence is controlled by time-evolving networks that describe the temporal transition of interactions among senescence regulators. Here, we present time-evolving networks for NAM/ATAF/CUC (NAC) transcription factors in Arabidopsis during leaf aging. The most evident characteristic of these time-dependent networks was a shift from positive to negative regulation among NACs at a presenescent stage. ANAC017, ANAC082, and ANAC090, referred to as a "NAC troika," govern the positive-to-negative regulatory shift. Knockout of the NAC troika accelerated senescence and the induction of other NACs, whereas overexpression of the NAC troika had the opposite effects. Transcriptome and molecular analyses revealed shared suppression of senescence-promoting processes by the NAC troika, including salicylic acid (SA) and reactive oxygen species (ROS) responses, but with predominant regulation of SA and ROS responses by ANAC090 and ANAC017, respectively. Our time-evolving networks provide a unique regulatory module of presenescent repressors that direct the timely induction of senescence-promoting processes at the presenescent stage of leaf aging.
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Arabidopsis/crecimiento & desarrollo , Senescencia Celular , Redes Reguladoras de Genes , Hojas de la Planta/crecimiento & desarrollo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Mutación , Fenotipo , Desarrollo de la Planta , Hojas de la Planta/genética , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Factores de Tiempo , TranscriptomaRESUMEN
BACKGROUND: Studies have shown that the prognosis of the treatment of methicillin-susceptible S. aureus (MSSA) with glycopeptides is inferior compared to treatment with ß-lactam. However, there are only few studies comparing treatment with antistaphylococcal penicillin alone to glycopeptide treatment. The aim of this study was to compare the efficacy of nafcillin, an antistaphylococcal penicillin, with that of glycopeptides as a definitive therapy for MSSA bacteremia. METHODS: Patients with MSSA bacteremia recruited from a tertiary referral hospital were enrolled in this retrospective cohort study. Demographic characteristics, laboratory data, and clinical outcome of the treatment were compared between a group receiving nafcillin and a group receiving glycopeptides. RESULTS: A total of 188 patients with MSSA bacteremia were included in this study. The glycopeptide group had a higher rate of malignancy (28.6 vs. 60.8%, p < 0.001) and proportion of healthcare-associated infections (47.3 vs. 72.2%, p < 0.001) compared to the nafcillin group. The ratio of skin and soft tissue infections (30.0 vs. 16.7%, p = 0.037) and bone and joint infections (17.8 vs. 6.3%, p = 0.022), as well as levels of C-reactive protein (139.60 vs. 107.61 mg/dL, p = 0.022) were higher in the nafcillin group. All-cause 28-day mortality was significantly high in the glycopeptide group (7.7 vs. 20.6%, p = 0.013). CONCLUSION: In patients with MSSA bacteremia, all-cause 28-day mortality rate was higher in a group treated with glycopeptides than in a group treated with nafcillin. Therefore, the use of nafcillin should be considered as a definitive therapy for MSSA bacteremia.
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Antibacterianos/uso terapéutico , Glicopéptidos/uso terapéutico , Nafcilina/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Adulto , Anciano , Antibacterianos/farmacología , Bacteriemia/tratamiento farmacológico , Proteína C-Reactiva/análisis , Estudios de Cohortes , Infección Hospitalaria/complicaciones , Femenino , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Masculino , Meticilina/farmacología , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Infecciones Estafilocócicas/complicaciones , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/mortalidad , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificación , Centros de Atención TerciariaRESUMEN
OBJECTIVES: This study aimed to evaluate the safety of ridge preservation/augmentation procedures when performed at compromised extraction sockets. METHODS: Patients subject to ridge preservation/augmentation at periodontally compromised sockets at Seoul National University Dental Hospital (SNUDH) were evaluated in a chart review. Tooth extractions due to acute infection were not included in our study as chronically formed lesions are the only lesions that can be detected from radiographic images. If inflammatory symptoms persisted following ridge preservation/augmentation and antimicrobial and anti-inflammatory therapy, the patient was categorized as a re-infection case and implanted biomaterial removed. RESULTS: Of 10,060 patients subject to tooth extractions at SNUDH, 2011 through 2015, 297 cases meeting inclusion criteria were reviewed. The severity and type of lesions were not specific because extracting data was only done by radiographic images and chart records. The review identified eight patients exhibiting inflammatory symptoms that required additional antimicrobial and anti-inflammatory therapy. Within this group, re-infection occurred in two patients requiring biomaterials removal. The final safety rate for the ridge preservation/augmentation was 99.3%. None of the demographic factors, systemic conditions or choice of biomaterial affected the safety of ridge preservation/augmentation. CONCLUSION: Alveolar ridge preservation/augmentation at periodontally compromised sockets appears safe following thorough removal of infectious source.
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Pérdida de Hueso Alveolar/cirugía , Aumento de la Cresta Alveolar/métodos , Seguridad del Paciente , Enfermedades Periodontales/cirugía , Extracción Dental , Alveolo Dental/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVES: This study aimed to evaluate the dynamics of newly bone formation and dimensional change in diseased extraction sockets using Bio-Oss® Collagen with or without a collagen membrane. MATERIAL AND METHODS: In six beagle dogs, right and left 3rd and 4th mandibular premolars were hemisected and the distal roots were removed. Combined endodontic-periodontic lesions were induced in all sites using black silk, collagen sponge, endodontic files, and application of Porphyromonas gingivalis. After 4 months, among 4 premolars, three teeth were randomly selected per dog and allocated to the following experimental groups: Control group (no treatment but debridement), Test 1 group (only Bio-Oss® Collagen graft), and Test 2 group (Bio-Oss® Collagen graft with a collagen membrane). After 7 months from the baseline, the beagle dogs were sacrificed for histomorphometric and Micro-CT analysis. RESULTS: The vertical distance between buccal and lingual crests in the Control group (2.22 ± 0.26 mm) and Test 2 group (1.80 ± 0.16 mm) was significantly different. The socket of the Test 2 group (27.04 ± 5.25%) was occupied by a greater quantity of bone graft compared to the Test 1 group (18.49 ± 2.11%). CONCLUSION: Ridge preservation in diseased extraction sockets could compensate for buccal bone resorption by contact osteogenesis surrounding the bone graft particles at the bucco-coronal area during socket healing, and the application of a collagen membrane at the entrance of the socket is useful for preserving graft material at the coronal part of the socket.
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Infecciones por Bacteroidaceae/fisiopatología , Regeneración Ósea , Sustitutos de Huesos , Colágeno , Minerales , Alveolo Dental/fisiología , Cicatrización de Heridas , Animales , Enfermedad Crónica , Modelos Animales de Enfermedad , Perros , Inflamación , Membranas Artificiales , Porphyromonas gingivalis , Extracción Dental , Alveolo Dental/citología , Alveolo Dental/diagnóstico por imagen , Alveolo Dental/microbiología , Microtomografía por Rayos XRESUMEN
Ubiquitination-mediated protein degradation via Really Interesting New Gene (RING) E3 ligase plays an important role in plant responses to abiotic stress conditions. Many plant studies have found that RING proteins regulate the perception of various abiotic stresses and signal transduction. In this study, Oryza sativa salt-induced RING Finger Protein 1 (OsSIRP1) gene was selected randomly from 44 Oryza sativa RING Finger Proteins (OsRFPs) genes highly expressed in rice roots exposed to salinity stress. Transcript levels of OsSIRP1 in rice leaves after various stress treatments, including salt, heat, drought and hormone abscisic acid (ABA), were observed. Poly-ubiquitinated products of OsSIRP1 were investigated via an in vitro ubiquitination assay.35S:OsSIRP1-EYFP was distributed in the cytosol of untreated and salt-treated rice protoplasts. Heterogeneous overexpression of OsSIRP1 in Arabidopsis reduced tolerance for salinity stress during seed germination and root growth. Our findings indicate that OsSIRP1 acts as a negative regulator of salinity stress tolerance mediated by the ubiquitin 26S proteasome system.
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Genoma de Planta/genética , Oryza/fisiología , Reguladores del Crecimiento de las Plantas/metabolismo , Proteínas de Plantas/metabolismo , Cloruro de Sodio/farmacología , Ácido Abscísico/metabolismo , Secuencia de Aminoácidos , Arabidopsis/genética , Arabidopsis/fisiología , Sequías , Regulación de la Expresión Génica de las Plantas , Oryza/citología , Oryza/genética , Filogenia , Hojas de la Planta/citología , Hojas de la Planta/genética , Hojas de la Planta/fisiología , Proteínas de Plantas/genética , Raíces de Plantas/citología , Raíces de Plantas/genética , Raíces de Plantas/fisiología , Complejo de la Endopetidasa Proteasomal/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , ARN Mensajero/genética , Salinidad , Alineación de Secuencia , Estrés Fisiológico , UbiquitinaciónRESUMEN
MAIN CONCLUSION: In this study, our findings regarding the regulation of GA irradiation-induced OsGIRP1 in relation to the levels of photosynthesis-related proteins such as OsrbcL1 and OsrbcS1 and hypersensitive responses of overexpressing plants to GR irradiation provide insight into the molecular functions of OsGIRP1 as a negative regulator in response to the stress of radiation. The RING (Really Interesting New Gene) finger proteins are known to play crucial roles in various abiotic stresses in plants. Here, we report on RING finger E3 ligase, Oryza sativa gamma rays-induced RING finger protein1 gene (OsGIRP1), which is highly induced by gamma rays (GR) irradiation. In vitro ubiquitination assay demonstrated that a single amino acid substitution (OsGIRP1(C196A)) of the RING domain showed no E3 ligase activity, supporting the notion that the activity of most E3s is specified by a RING domain. We isolated at least 6 substrate proteins of OsGIRP1, including 2 Rubisco subunits, OsrbcL1 and OsrbcSl, via yeast two-hybridization and bimolecular fluorescence complementation assays. OsGIRP1 and its partner proteins were targeted to the cytosol and the cytosol or chloroplasts, respectively; however, florescence signals of the complexes with OsGIPR1 were observed in the cytosol. Protein degradation in cell extracts showed that OsGIRP1 mediates proteolysis of 2 substrates, OsrbcS1 and OsrbcL1, via the 26S proteasome degradation pathway. The Arabidopsis plants overexpressing OsGIRP1 clearly exhibited increased sensitivity to GR irradiation. These results might suggest that OsGIRP1 acts as a negative regulator of GR response to mediate the degradation of photosynthesis-related proteins.
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Rayos gamma , Oryza/enzimología , Fotosíntesis , Proteínas de Plantas/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Secuencia de Aminoácidos , Arabidopsis/genética , Datos de Secuencia Molecular , Oryza/efectos de la radiación , Proteínas de Plantas/química , Proteínas de Plantas/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Unión Proteica , Proteolisis , Homología de Secuencia de Aminoácido , Ubiquitina-Proteína Ligasas/química , Ubiquitina-Proteína Ligasas/genética , Regulación hacia ArribaRESUMEN
Nanofibrous matrices are attractive scaffolding platforms for tissue regeneration. Modification of the nanofiber surface, particularly with biological proteins, improves cellular interactions. Here, we loaded basic fibroblast growth factor (bFGF) onto mineralized nanofibers and investigated the effect on adhesion and proliferation of rat mesenchymal stem cells. bFGF loading was significantly higher on the mineralized nanofiber than on the non-mineralized one. Release of bFGF from the mineralized nanofibers was continuous over 2 weeks. Cells cultured on the bFGF-loaded nanofiber attached and proliferated in significantly higher numbers than those on the bFGF-free nanofiber. bFGF-receptor inhibition study confirmed the biological role played by the loaded bFGF. This study details the advantages of the mineralized nanofiber surface for the loading and delivery bFGF, and thus the bFGF-loaded nanofiber scaffold may be useful for tissue repair and regeneration.
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Biopolímeros/metabolismo , Proliferación Celular , Portadores de Fármacos/metabolismo , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/fisiología , Nanofibras , Animales , Adhesión Celular , RatasRESUMEN
Several mammals--including sheep, mice, cows, goats, pigs, rabbits, cats, a mule, a horse and a litter of three rats--have been cloned by transfer of a nucleus from a somatic cell into an egg cell (oocyte) that has had its nucleus removed. This technology has not so far been successful in dogs because of the difficulty of maturing canine oocytes in vitro. Here we describe the cloning of two Afghan hounds by nuclear transfer from adult skin cells into oocytes that had matured in vivo. Together with detailed sequence information generated by the canine-genome project, the ability to clone dogs by somatic-cell nuclear transfer should help to determine genetic and environmental contributions to the diverse biological and behavioural traits associated with the many different canine breeds.
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Clonación de Organismos , Perros/crecimiento & desarrollo , Perros/genética , Envejecimiento , Animales , Perros/clasificación , Perros/embriología , Transferencia de Embrión , Femenino , Fibroblastos/citología , Masculino , Repeticiones de Microsatélite/genética , Técnicas de Transferencia Nuclear , Donación de Oocito , Oocitos/citología , Oocitos/fisiología , Oocitos/trasplante , Embarazo , Piel/citología , Factores de TiempoRESUMEN
PURPOSE: Previous studies have solely focused on fresh extraction sockets, whereas in clinical settings, alveolar sockets are commonly associated with chronic inflammation. Because the extent of tissue destruction varies depending on the origin and the severity of inflammation, infected alveolar sockets may display various configurations of their remaining soft and hard tissues following tooth extraction. The aim of this study was to classify infected alveolar sockets and to provide the appropriate treatment approaches. METHODS: A proposed classification of extraction sockets with chronic inflammation was developed based upon the morphology of the bone defect and soft tissue at the time of tooth extraction. The prevalence of each type of the suggested classification was determined retrospectively in a cohort of patients who underwent, between 2011 and 2015, immediate bone grafting procedures (ridge preservation/augmentation) after tooth extractions at Seoul National University Dental Hospital. RESULTS: The extraction sockets were classified into 5 types: type I, type II, type III, type IV (A & B), and type V. In this system, the severity of bone and soft tissue breakdown increases from type I to type V, while the reconstruction potential and treatment predictability decrease according to the same sequence of socket types. The retrospective screening of the included extraction sites revealed that most of the sockets assigned to ridge preservation displayed features of type IV (86.87%). CONCLUSIONS: The present article classified different types of commonly observed infected sockets based on diverse levels of ridge destruction. Type IV sockets, featuring an advanced breakdown of alveolar bone, appear to be more frequent than the other socket types.
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The mi-iuy croaker Miichthys miiuy has immense commercial value in the Republic of Korea. The red drum Sciaenops ocellatus is widely produced by aquaculture, although its price is approximately 25% that of M. miiuy. S. ocellatus has black spots on its tail, enabling it to be distinguished from M. miiuy based on appearance. However, identifying S. ocellatus after simple processing steps, such as skin removal and dicing, is difficult. Certain traders misrepresent and sell S. ocellatus as M. miiuy or cultured M. miiuy for illegal economical gain. Therefore, an accurate and rapid identification method is required to distinguish between M. miiuy and S. ocellatus in the field. Here, a method for rapid field identification was developed based on species-specific primers using a portable ultra-fast PCR instrument. The ultra-fast real-time PCR method can complete the entire analytical procedure, including DNA isolation, amplification, and detection, within 30 min, thus maintaining the accuracy of identifying M. miiuy and S. ocellatus products on site. Forty-nine commercial products were tested, and all samples were successfully identified. Thus, the developed method is rapid, efficient tool for ensuring consumer protection. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-00954-4.
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BACKGROUND: To minimize alveolar bone resorption, alveolar ridge preservation (ARP) has been proposed. Recently, interest in improving the feasibility of implant placement has gradually increased, especially in situations of infection such as periodontal and/or endodontic lesions. The aim of this study was to investigate if ARP improves feasibility of implant placement compared with no ARP in periodontally compromised sites. Secondary endpoints were the necessity of bone graft at the time of implant placement and implant failure before loading at ARP compared with no ARP. MATERIAL AND METHODS: This retrospective study was performed using dental records and radiographs obtained from patients who underwent tooth extraction due to chronic periodontal pathology. Outcomes including the feasibility of implant placement, horizontal bone augmentation, vertical bone augmentation, sinus floor elevation, total bone augmentation at the time of implant placement, and implant failure before loading were investigated. Multivariable logistic regression analysis was performed to examine the influence of multiple variables on the clinical outcomes. RESULTS: In total, 418 extraction sites (171 without ARP and 247 with ARP) in 287 patients were included in this study. The ARP group (0.8%) shows significantly lower implant placement infeasibility than the no ARP group (4.7%). Horizontal and vertical bone augmentations were significantly influenced by location and no ARP. Total bone augmentation was significantly influenced by sex, location, and no ARP. CONCLUSION: ARP in periodontally compromised sites may improve the feasibility of implant placement. In addition, ARP attenuate the severity of the bone augmentation procedure.
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Aumento de la Cresta Alveolar , Elevación del Piso del Seno Maxilar , Proceso Alveolar/diagnóstico por imagen , Humanos , Estudios Retrospectivos , Alveolo Dental/diagnóstico por imagenRESUMEN
Bone/cartilage interfacial tissue engineering needs to satisfy the differential properties and architectures of the osteochondral region. Therefore, biphasic or multiphasic scaffolds that aim to mimic the gradient hierarchy are widely used. Here, we find that two differently structured (topographically) three-dimensional scaffolds, namely, "dense" and "nanofibrous" surfaces, show differential stimulation in osteo- and chondro-responses of cells. While the nanofibrous scaffolds accelerate the osteogenesis of mesenchymal stem cells, the dense scaffolds are better in preserving the phenotypes of chondrocytes. Two types of porous scaffolds, generated by a salt-leaching method combined with a phase-separation process using the poly(lactic acid) composition, had a similar level of porosity (~90%) and pore size (~150 µm). The major difference in the surface nanostructure led to substantial changes in the surface area and water hydrophilicity (nanofibrous â« dense); as a result, the nanofibrous scaffolds increased the cell-to-matrix adhesion of mesenchymal stem cells significantly while decreasing the cell-to-cell contracts. Importantly, the chondrocytes, when cultured on nanofibrous scaffolds, were prone to lose their phenotype, including reduced chondrogenic expressions (SOX-9, collagen type II, and Aggrecan) and glycosaminoglycan content, which was ascribed to the enhanced cell-matrix adhesion with reduced cell-cell contacts. On the contrary, the osteogenesis of mesenchymal stem cells was significantly accelerated by the improved cell-to-matrix adhesion, as evidenced in the enhanced osteogenic expressions (RUNX2, bone sialoprotein, and osteopontin) and cellular mineralization. Based on these findings, we consider that the dense scaffold is preferentially used for the chondral-part, whereas the nanofibrous structure is suitable for osteo-part, to provide an optimal biphasic matrix environment for osteochondral tissue engineering.
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The stability of peri-implant tissue is essential for the long-term success of dental implants. Although various types of implant connections are used, little is known about the effects of the physical mechanisms of dental implants on the stability of peri-implant tissue. This review summarizes the relevant literature to establish guidelines regarding the effects of connection type between abutments and implants in soft and hard tissues. Soft tissue seals can affect soft tissue around implants. In external connections, micromobility between the abutment and the hex component of the implant, resulting from machining tolerance, can destroy the soft tissue seal, potentially leading to microbial invasion. Internal friction connection implants induce strain on the surrounding bone via implant wall expansion that translates into masticatory force. This strain is advantageous because it increases the amount and quality of peri-implant bone. The comparison of internal and external connections, the two most commonly used connection types, reveals that internal friction has a positive influence on both soft and hard tissues.
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BACKGROUND: This experimental study aims to evaluate the effect of hyaluronic acid on healing of infected extraction sockets compared with recombinant human bone morphogenetic protein-2 (rhBMP-2). METHODS: Both third and fourth mandibular premolars of six beagle dogs were hemisected, and the distal roots were extracted at baseline. Subsequently, combined endodontic-periodontic lesions were induced at the remaining mesial roots. After 4 months, the mesial roots on both sides of the mandible were removed. Four sockets per dog were randomly allocated to four groups: Group 1, Control; Group 2, only absorbable collagen sponge (ACS: carrier); Group 3, 1% hyaluronic acid (HA) gel + ACS; and Group 4, rhBMP-2 + ACS. After 3 months of healing, the dogs were euthanized for microcomputed tomography and histologic analysis. RESULTS: After the lesion induction period (4 months), communication between the periodontal lesion and endodontic periapical lesion was observed at all remaining mesial roots. Alveolar bone overgrowth was observed in groups 3 and 4, but bone volume density was not significantly different among all groups. At the crestal portion, mineralization, and osteocalcin expression were higher in groups 3 and 4 than in groups 1 and 2. CONCLUSION: Treatment with HA can promote bone formation and improve the wound healing rate comparable to rhBMP-2 in infected extraction sockets.
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Regeneración Ósea , Ácido Hialurónico , Animales , Proteína Morfogenética Ósea 2 , Perros , Humanos , Proteínas Recombinantes , Factor de Crecimiento Transformador beta , Microtomografía por Rayos XRESUMEN
Current chemotherapy regimens have certain limitations in improving the survival rates of patients with advanced ovarian cancer. Hepatocyte growth factor (HGF) is important in ovarian cancer cell migration and invasion. This study assessed the effects of YYB-101, a humanized monoclonal anti-HGF antibody, on the growth and metastasis of ovarian cancer cells. YYB-101 suppressed the phosphorylation of the HGF receptor c-MET and inhibited the migration and invasion of SKOV3 and A2780 ovarian cancer cells. Moreover, the combination of YYB-101 and paclitaxel synergistically inhibited tumor growth in an in vivo ovarian cancer mouse xenograft model and significantly increased the overall survival (OS) rate compared with either paclitaxel or YYB-101 alone. Taken together, these findings suggest that YYB-101 has therapeutic potential in ovarian cancer when combined with conventional chemotherapy agents.
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The mechanisms of 12(S)-hydroperoxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid (12(S)-HPETE)-induced scratching were studied in ICR mice. In a recent paper, we demonstrated that the 12(S)-HPETE-induced scratching was reduced not by U75302 (BLT(1) receptor antagonist), but by LY255283 (BLT(2) receptor antagonist). In the present study, we tested various compounds to elucidate the mechanism of 12(S)-HPETE-induced scratching relating to transient receptor potential vanilloid type-1 (TRPV1), histamine receptor (H(1)) and several serotonin receptors (5-HT(1), 5-HT(2), and 5-HT(3)). As a result, 12(S)-HPETE-induced scratching was suppressed by capsaicin (TRPV1 receptor agonist), but not by capsazepine (TRPV1 receptor antagonist). Additionally, chlopheniramine (H(1) receptor antagonist) did not suppress 12(S)-HPETE-induced scratching, but cyproheptadine (H(1) receptor and serotonin 5-HT(2) receptor antagonist) potently suppressed the same response. Therefore, we tested several serotonin receptor antagonists to explain the detailed mechanisms relating to serotonin receptors. The scratching was reduced by WAY100635 (5-HT(1) receptor antagonist), or ketanserin (5-HT(2) receptor antagonist), but not by ondansetron (5-HT(3) receptor antagonist), after intradermal injection of 12(S)-HPETE. These results suggest that serotonin 5-HT(1/2) receptors are implicated in 12(S)-HPETE-induced scratching in ICR mice and that the TRPV1 receptor might not be directly related to 12(S)-HPETE-induced scratching.
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Leucotrienos/farmacología , Prurito/inducido químicamente , Receptores de Serotonina 5-HT1/efectos de los fármacos , Receptores de Serotonina 5-HT2/efectos de los fármacos , Animales , Conducta Animal , Masculino , Ratones , Ratones Endogámicos ICR , Receptores Histamínicos H1/efectos de los fármacos , Receptores Histamínicos H1/metabolismo , Receptores de Serotonina 5-HT1/metabolismo , Receptores de Serotonina 5-HT2/metabolismo , Receptores de Serotonina 5-HT3/efectos de los fármacos , Receptores de Serotonina 5-HT3/metabolismo , Canales Catiónicos TRPV/efectos de los fármacos , Canales Catiónicos TRPV/metabolismoRESUMEN
Sphingosylphosphorylcholine (SPC) is upregulated in the stratum corneum of atopic dermatitis patients by sphingomyelin deacylase. We conducted an investigation, both to confirm that intradermal injection of SPC elicits scratching in mice, and to elucidate the detailed mechanism of the SPC-induced itch-scratch response. Intradermal administration of SPC increased the incidence of scratching behavior in a dose-dependent manner. SPC-induced scratching could be suppressed, significantly, by the mu-opoid receptor antagonist, naltrexon, the vaniloid receptor agonist, capsaicin, and the histamine H1 receptor antagonist ketotifen. d-erythro SPC, one of the SPC stereotypes, could elicit the scratch response, but not l-threo SPC. Y-27632 (1 mg/kg, an inhibitor of Rho-associated protein kinase (ROCK)), was found to suppress SPC-induced scratching. Both the stereospecificity of SPC and the involvement of the Rho/ROCK pathway suggested that SPC-induced scratching is related to the receptor.
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Amidas/farmacología , Antipruriginosos/farmacología , Relajantes Musculares Centrales/farmacología , Fosforilcolina/análogos & derivados , Prurito/inducido químicamente , Prurito/tratamiento farmacológico , Piridinas/farmacología , Esfingosina/análogos & derivados , Animales , Conducta Animal/efectos de los fármacos , Capsaicina/farmacología , Relación Dosis-Respuesta a Droga , Inyecciones Intradérmicas , Cetotifen/farmacología , Masculino , Ratones , Ratones Endogámicos ICR , Naltrexona/farmacología , Antagonistas de Narcóticos/farmacología , Fosforilcolina/administración & dosificación , Fosforilcolina/farmacología , Prurito/psicología , Esfingosina/administración & dosificación , Esfingosina/farmacología , Quinasas Asociadas a rho/metabolismoRESUMEN
The itch-associated responses evoked by intradermal injection of 12(S)-HPETE and leukotriene B4 were compared in ICR-mice. 12(S)-HPETE and leukotriene B4 (0.01-0.2 nmol/site) induced scratching of the injected site, respectively; the dose-responses were a peak at 0.05 nmol/site (12(S)-HPETE) or 0.03 nmol/site (leukotriene B4). The scratching response by 12(S)-HPETE (0.05 nmol/site) started within 1 min, peaked in the first 10 min period, had almost subsided by 25 min whereas the effect of leukotriene B4 peaked in the second 10 min. The effect of leukotriene B4 is slightly stronger than that of 12(S)-HPETE in 40 min of count. The scratching induced by 12(S)-HPETE was inhibited by capsaicin, naltrexon, and LY255283. These results suggest the possibility that 12-lipoxygenase product can be added to a new member of an endogenous itch mediator in the skin.
Asunto(s)
Prurito/inducido químicamente , Animales , Capsaicina/farmacología , Relación Dosis-Respuesta a Droga , Leucotrieno B4/farmacología , Leucotrienos/farmacología , Masculino , Ratones , Ratones Endogámicos ICR , Naltrexona/farmacología , Receptores de Leucotrieno B4/antagonistas & inhibidoresRESUMEN
This study was designed to determine whether dietary epigallocatechin-3-gallate (EGCG), the most abundant catechin polyphenol in green tea, can protect the liver from cytochrome P450 2E1 (CYP2E1)-dependent alcoholic liver damage. Compared with an ethanol group, when EGCG was present in the ethanol diet, the formation of a fatty liver was significantly reduced and the serum aspartate transaminase (AST) and alanine transaminase (ALT) levels were much lower. Ethanol treatment significantly elevated hepatic CYP2E1 expression while simultaneously reducing hepatic phospho-acetyl CoA carboxylase (p-ACC) and carnitine palmitoyl-transferase 1 (CPT-1) levels. While EGCG markedly reversed the effect of ethanol on hepatic p-ACC and CPT-1 levels, it had no effect on the ethanol-induced elevation in CYP2E1 expression. EGCG prevents ethanol-induced hepatotoxicity and inhibits the development of a fatty liver. These effects were associated with improvements in p-ACC and CPT-1 levels. The use of EGCG might be useful in treating patients with an alcoholic fatty liver.