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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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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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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.
Subject(s)
Alveolar Ridge Augmentation , Sinus Floor Augmentation , Alveolar Process/diagnostic imaging , Humans , Retrospective Studies , Tooth Socket/diagnostic imagingABSTRACT
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.
Subject(s)
Alveolar Bone Loss , Alveolar Ridge Augmentation , Animals , Cattle , Alveolar Bone Loss/diagnostic imaging , Alveolar Bone Loss/surgery , Alveolar Process/diagnostic imaging , Alveolar Process/surgery , Tooth Extraction , Tooth Socket/diagnostic imaging , Tooth Socket/surgery , HumansABSTRACT
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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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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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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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.
Subject(s)
Bone Regeneration , Hyaluronic Acid , Animals , Bone Morphogenetic Protein 2 , Dogs , Humans , Recombinant Proteins , Transforming Growth Factor beta , X-Ray MicrotomographyABSTRACT
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.
Subject(s)
Arabidopsis/growth & development , Cellular Senescence , Gene Regulatory Networks , Plant Leaves/growth & development , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Gene Expression Regulation, Plant , Mutation , Phenotype , Plant Development , Plant Leaves/genetics , Repressor Proteins/genetics , Repressor Proteins/metabolism , Time Factors , TranscriptomeABSTRACT
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.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Glycopeptides/therapeutic use , Nafcillin/therapeutic use , Staphylococcal Infections/drug therapy , Adult , Aged , Anti-Bacterial Agents/pharmacology , Bacteremia/drug therapy , C-Reactive Protein/analysis , Cohort Studies , Cross Infection/complications , Female , Hospital Mortality , Humans , Intensive Care Units , Male , Methicillin/pharmacology , Middle Aged , Proportional Hazards Models , Retrospective Studies , Staphylococcal Infections/complications , Staphylococcal Infections/microbiology , Staphylococcal Infections/mortality , Staphylococcus aureus/drug effects , Staphylococcus aureus/isolation & purification , Tertiary Care CentersABSTRACT
BACKGROUND: During pulmonary artery catheter (PAC) implantation, inaccurate measurements of hemodynamic parameters due to infection or thrombosis of PAC can result in severe complications. METHOD: In order to develop a new PAC material, we evaluated the antibacterial and antithrombotic activities of the two types of PAC (Swan Ganz catheter and prototype catheter) in 14 pigs. RESULTS: In the 3-day group, bacterial infection rate was not different between the two types of PAC. In the 7-day group, bacterial infection rate of the prototype catheter was twice as elevated as that of the Swan-Ganz catheter. In the 3-day group, thrombus formation rate of the prototype catheter was twice as elevated as that of the Swan-Ganz catheter. In the 7-day group, thrombus formation rate was the same for the two types of PAC. CONCLUSION: Here, we report an experimental pig model that confirms differences in antibacterial and antithrombotic activities.
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PURPOSE: Evidence on the outcomes of functional loading placed in recombinant human bone morphogenetic protein 2 (rhBMP-2)/acellular collagen sponge (ACS)-induced bone is lacking. The aim of this study was to verify whether guided bone regeneration (GBR) with rhBMP-2/ACS enhances regeneration of missing bone and osseointegration of dental implants subject to functional loading. MATERIALS AND METHODS: Two bilateral standardized large saddle-type defects (≈10 × 10 × 6 mm) were surgically created in each mandible of seven beagle dogs 2 months after tooth extraction. Defects were immediately reconstructed randomly using rhBMP-2 (O-BMP or InFuse) soaked in ACS, deproteinized bovine bone mineral (DBBM) granules, or ACS alone as surgical control and subsequently covered with collagen membrane. Screw-type sand-blasted, acid-etched dental implants were placed 3 months later into the reconstructed defects and into adjacent bone. Osseointegration was allowed to progress for 3 months before functional loading of 3 months until sacrifice. RESULTS: Significantly more bone fill was radiographically observed for GBR with rhBMP-2/ACS (O-BMP: 92.5%, InFuse: 79%) in comparison to the DBBM (52%) and ACS alone groups (56.6%). Osseointegration was achieved and maintained in all experimental defects challenged by prostheses-driven functional load. The bone density ranged from 37.49% in the ACS group to 64.9% in the rhBMP-2/ACS (InFuse) group with no significance. The highest mean percentage of BIC was found in rhBMP-2/ACS (InFuse: 52.98%) with no statistical difference. Crestal bone resorption was observed around implants placed in reconstructed areas without any significant difference. CONCLUSION: GBR with rhBMP-2/ACS provided the greatest bone fill among the three treatment procedures. GBR with rhBMP-2/ACS showed efficacy for placement, osseointegration, and functional loading of titanium implants in alveolar ridge defects.
Subject(s)
Bone Morphogenetic Protein 2/pharmacology , Bone Regeneration/drug effects , Dental Implants , Guided Tissue Regeneration, Periodontal/methods , Osseointegration/drug effects , Transforming Growth Factor beta/pharmacology , Absorbable Implants , Alveolar Bone Loss/surgery , Alveolar Process/pathology , Alveolar Ridge Augmentation , Animals , Bone Density/drug effects , Cattle , Dental Implantation, Endosseous , Disease Models, Animal , Dogs , Humans , Mandible/surgery , Recombinant Proteins/pharmacology , TitaniumABSTRACT
Porcine reproductive and respiratory syndrome virus (PRRSV) causes major economic losses in the swine industry worldwide. Vaccination is the most effective method to control the disease. In a previous study, a chimeric PRRSV named as K418 which had a genome composed of ORF 1 from the FL12 strain and ORF 2-7 from the Korean representative LMY strain was created. We constructed K418DM, K418 with deglycosylated glycoprotein 5 (GP5), to improve its humoral immunity. In the follow-up on in vivo and in vitro virological and serological tests, no back mutation in amino acids of GP5 associated with deglycosylation was shown after 9 passages on MARC-145 cells, whereas only one case of back mutation was detected after single passage in pig. In serological study, K418DM induced higher serum neutralization (SN) antibody and more limited viremia compared with those of K418 virus. In clinical trial and economic analysis, the K418DM elicited SN antibody titers and PRRSV-specific IgG over protection limit. From the economic viewpoint, there was statistically significant reduction in percentage of weak pigs. These results indicated that vaccination with the K418DM may provide enhanced protection for pigs in PRRS endemic situation and increase growth performance in commercial pig farms.
Subject(s)
Porcine respiratory and reproductive syndrome virus/immunology , Porcine respiratory and reproductive syndrome virus/pathogenicity , Viral Vaccines/immunology , Viral Vaccines/therapeutic use , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Porcine Reproductive and Respiratory Syndrome/immunology , Porcine Reproductive and Respiratory Syndrome/prevention & control , Porcine respiratory and reproductive syndrome virus/genetics , SwineABSTRACT
PURPOSE: The aim of the present exploratory study was to evaluate extraction socket healing at sites with a history of periodontal and endodontic pathology. METHODS: The mandibular 4th premolar teeth in 5 adult beagle dogs served as experimental units. Periodontal and endodontic lesions were induced in 1 premolar site in each animal using wire ligatures and pulpal exposure over 3 months (diseased sites). The contralateral premolar sites served as healthy controls. The mandibular 4th premolar teeth were then extracted with minimal trauma, followed by careful wound debridement. The animals were sacrificed at days 1, 7, 30, 60, and 90 post-extraction for analysis, and the healing patterns at the healthy and diseased extraction sites were compared using radiography, scanning electron microscopy, histology, and histometry. RESULTS: During the first 7 days of healing, a significant presence of inflammatory granulation tissue was noted at the diseased sites (day 1), along with a slightly accelerated rate of fibrin clot resolution on day 7. On day 30, the diseased extraction sites showed a greater percentage of persistent fibrous connective tissue, and an absence of bone marrow formation. In contrast, healthy sites showed initial signs of bone marrow formation on day 30, and subsequently a significantly greater proportion of mature bone marrow formation on both days 60 and 90. Radiographs exhibited sclerotic changes adjoining apical endodontic lesions, with scanning electron microscopy showing collapsed Volkmann canals protruding from these regions in the diseased sites. Furthermore, periodontal ligament fibers exhibited a parallel orientation to the alveolar walls of the diseased sites, in contrast to a perpendicular arrangement in the healthy sites. CONCLUSIONS: Within the limitations of this study, it appears that a history of periodontal and endodontic pathology may critically affect bone formation and maturation, leading to delayed and compromised extraction socket healing.
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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.
Subject(s)
Alveolar Bone Loss/surgery , Alveolar Ridge Augmentation/methods , Patient Safety , Periodontal Diseases/surgery , Tooth Extraction , Tooth Socket/surgery , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment OutcomeABSTRACT
Kikuchi-Fujimoto disease (KFD) is a rare, self-limiting disorder that typically affects the cervical lymph nodes (LNs). Although initially described in young women, KFD also occurs in men. There are no reports on the clinical manifestations and characteristics of male KFD patients. Therefore, this study was conducted to assess the incidence of KFD among males, as well as the most frequent clinical characteristics of these patients. A retrospective, cross-sectional study was performed at a tertiary hospital of patients pathologically confirmed as having KFD from LN biopsy specimens. Clinical and laboratory data, and treatment outcomes of the enrolled patients, were analyzed by gender. A total of 254 patients diagnosed with KFD were enrolled. There were 189 females and 65 males (2.9:1). The mean age was 32.6â±â11.3 years. Compared to the female patients, the males had more frequent manifestations of fever (48% vs 67%, Pâ=â0.008), headache (9% vs 20%, Pâ=â0.013), bilateral lymphadenopathy (31% vs 46%, Pâ=â0.029), thrombocytopenia (14% vs 29%, Pâ=â0.014), elevated C-reactive protein (CRP) (35% vs 78.4%, Pâ<â0.001), elevated liver enzymes (15% vs 41%, Pâ<â0.001), and elevated lactate dehydrogenase (LDH) (61% vs 80%, Pâ=â0.021). Male patients had fewer autoimmune features (9% vs 2%, Pâ=â0.043) and fewer positive antinuclear antibodies (32% vs 10%, Pâ=â0.006). In this study, 25.6% of the enrolled patients were male, with a 2.9:1 female-to-male sex ratio. Male patients showed a distinctive profile characterized by a higher frequency of fever, headache, bilateral lymphadenopathy, and thrombocytopenia, as well as elevated liver enzymes, CRP, and LDH.
Subject(s)
Histiocytic Necrotizing Lymphadenitis/epidemiology , Histiocytic Necrotizing Lymphadenitis/physiopathology , Adult , Antibodies, Antinuclear/blood , C-Reactive Protein/analysis , Cross-Sectional Studies , Female , Humans , Incidence , L-Lactate Dehydrogenase/blood , Liver Function Tests , Male , Middle Aged , Republic of Korea/epidemiology , Retrospective Studies , Sex FactorsABSTRACT
Hepatocyte growth factor (HGF) and its receptor, cMET, play critical roles in cell proliferation, angiogenesis and invasion in a wide variety of cancers. We therefore examined the anti-tumor activity of the humanized monoclonal anti-HGF antibody, YYB-101, in nude mice bearing human glioblastoma xenografts as a single agent or in combination with temozolomide. HGF neutralization, The extracellular signal-related kinases 1 and 2 (ERK1/2) phosphorylation, and HGF-induced scattering were assessed in HGF-expressing cell lines treated with YYB-101. To support clinical development, we also evaluated the preclinical pharmacokinetics and toxicokinetics in cynomolgus monkeys, and human and cynomolgus monkey tissue was stained with YYB-101 to test tissue cross-reactivity. We found that YYB-101 inhibited cMET activation in vitro and suppressed tumor growth in the orthotopic mouse model of human glioblastoma. Combination treatment with YYB-101 and temozolomide decreased tumor growth and increased overall survival compared with the effects of either agent alone. Five cancer-related genes (TMEM119, FST, RSPO3, ROS1 and NBL1) were overexpressed in YYB-101-treated mice that showed tumor regrowth. In the tissue cross-reactivity assay, critical cross-reactivity was not observed. The terminal elimination half-life was 21.7 days. Taken together, the in vitro and in vivo data demonstrated the anti-tumor efficacy of YYB-101, which appeared to be mediated by blocking the HGF/cMET interaction. The preclinical pharmacokinetics, toxicokinetics and tissue cross-reactivity data support the clinical development of YYB-101 for advanced cancer.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Neutralizing/therapeutic use , Antineoplastic Agents, Immunological/pharmacology , Brain Neoplasms/drug therapy , Glioblastoma/drug therapy , Hepatocyte Growth Factor/antagonists & inhibitors , Animals , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/immunology , Antibodies, Neutralizing/adverse effects , Antibodies, Neutralizing/immunology , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/therapeutic use , Dogs , Female , Hep G2 Cells , Hepatocyte Growth Factor/immunology , Humans , Macaca fascicularis , Madin Darby Canine Kidney Cells , Mice , Mice, Inbred BALB C , Mice, Nude , Proto-Oncogene Proteins c-met/antagonists & inhibitors , Proto-Oncogene Proteins c-met/immunologyABSTRACT
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.
Subject(s)
Bacteroidaceae Infections/physiopathology , Bone Regeneration , Bone Substitutes , Collagen , Minerals , Tooth Socket/physiology , Wound Healing , Animals , Chronic Disease , Disease Models, Animal , Dogs , Inflammation , Membranes, Artificial , Porphyromonas gingivalis , Tooth Extraction , Tooth Socket/cytology , Tooth Socket/diagnostic imaging , Tooth Socket/microbiology , X-Ray MicrotomographyABSTRACT
Providing a nanotopological physical cue in concert with a bioactive chemical signal within 3D scaffolds, while it being considered a promising approach for bone regeneration, has yet to be explored. Here, we develop 3D porous scaffolds that are networked to be a nanofibrous structure and incorporated with bioactive glass nanoparticles (BGn) to tackle this issue. The presence of BGn and nanofibrous structure (BGn + nanofibrous) substantially increased the surface area, hydro-affinity and protein loading capacity of scaffolds. In particular, the BGn released Si and Ca ions to the levels known to be biologically effective, offering the bone scaffold an ability to deliver therapeutic ions. The mesenchymal stem cells (MSCs) from rats exhibited significantly accelerated adhesion events including cell anchorage, cytoskeletal extensions, and the expression of adhesion signaling molecules on the BGn/nanofibrous scaffolds. The cells gained a more rapid proliferation and migration (penetration) ability over 2 weeks within the BGn + nanofibrous scaffolds than within either nanofibrous or BGn scaffolds. The osteogenesis of MSCs, as confirmed by the expressions of bone-associated genes and proteins, as well as the cellular mineralization was significantly stimulated by the BGn and nanofibrous topology in a synergistic manner. The behaviors of endothelial cells (HUVECs) including cell migration and tubule networking were also enhanced when influenced by the BGn and nanofibrous scaffolds (but more by BGn than by nanofiber). A subcutaneous tissue implantation of the scaffolds further evidenced the in vivo stimulation of neo-blood vessel formation by the BGn + nanofibrous cues, suggesting the possible promising role in bone regeneration. Taken together, the therapeutic ions and nanofibrous topology implemented within 3D scaffolds are considered to play synergistic actions in osteogenesis and angiogenesis, implying the potential usefulness of the BGn + nanofibrous scaffolds for bone tissue engineering.
Subject(s)
Nanofibers , Nanoparticles , Animals , Bone Regeneration , Cell Differentiation , Cells, Cultured , Cues , Mesenchymal Stem Cells , Osteogenesis , Rats , Tissue Engineering , Tissue ScaffoldsABSTRACT
BACKGROUND: Adverse drug reactions (ADRs) are any unwanted/uncomfortable effects from medication resulting in physical, mental, and functional injuries. Antibiotics account for up to 40.9% of ADRs and are associated with several serious outcomes. However, few reports on ADRs have evaluated only antimicrobial agents. In this study, we investigated antibiotic-related ADRs at a tertiary care hospital in South Korea. METHODS: This is a retrospective cohort study that evaluated ADRs to antibiotics that were reported at a 2400-bed tertiary care hospital in 2015. ADRs reported by physicians, pharmacists, and nurses were reviewed. Clinical information reported ADRs, type of antibiotic, causality assessment, and complications were evaluated. RESULTS: 1,277 (62.8%) patients were considered antibiotic-related ADRs based on the World Health Organization-Uppsala Monitoring Center criteria (certain, 2.2%; probable, 35.7%; and possible, 62.1%). Totally, 44 (3.4%) patients experienced serious ADRs. Penicillin and quinolones were the most common drugs reported to induce ADRs (both 16.0%), followed by third-generation cephalosporins (14.9%). The most frequently experienced side effects were skin manifestations (45.1%) followed by gastrointestinal disorders (32.6%). CONCLUSION: Penicillin and quinolones are the most common causative antibiotics for ADRs and skin manifestations were the most frequently experienced symptom.