116 research outputs found

    Accuracy management survey of nucleic acid amplification tests using inactivated SARS-CoV-2 in Hiroshima Prefecture

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    At the beginning of 2020, the number of laboratories performing SARS-CoV-2 testing increased with the rapid expansion of COVID-19 in Hiroshima Prefecture. Thus, it is necessary to compare and verify the validity of the test results among local laboratories. In this study, we distributed the same standard samples to laboratories that performed COVID-19 testing using the nucleic acid amplification method and confirmed the accuracy of the tests. The SARS-CoV-2 strain distributed by the National Institute of Infectious Diseases (NIID), Japan, was used for testing. As measured by RT-qPCR, a specific amount of the virus was inactivated by ethanol and dried as specimens for distribution. This study included 27 tests performed at 15 laboratories conducting or planning to conduct nucleic acid amplification tests (RT-qPCR and LAMP methods) for SARSCoV-2. The detection limit of each test method was set at the value provided by the NIID. The accuracy of the tests was examined to determine whether they met the required accuracy criteria. SARS-CoV-2 genomic RNA was reliably detected in all 27 tests. The inactivated specimens used in this study were safe to distribute and could be used as positive controls for all methods.This study was supported by a grant from the Government-Academia Collaboration of Hiroshima Prefecture and by a research grant for COVID-19 from AMED, Japan under Grant Number 20he0622011h0001(to J. T.)

    Pretreatment serum FGF-23 levels predict the efficacy of calcitriol therapy in dialysis patients

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    Pretreatment serum FGF-23 levels predict the efficacy of calcitriol therapy in dialysis patients.BackgroundThe predictor for the result of calcitriol therapy would be useful in the clinical practice of secondary hyperparathyroidism. Fibroblast growth factor-23 (FGF-23) is a newly found circulating phosphaturic factor. Its circulating level is elevated in uremia.MethodsDialysis patients with plasma intact parathyroid hormone (iPTH) levels greater than 300 pg/mL were included in the study. Calcitriol was intravenously injected three times a week. The patients whose plasma iPTH levels dropped below 300 pg/mL within 24 weeks were defined as those who had been successfully treated. A sandwich enzyme-linked immunosorbent assay (ELISA) system that detects human FGF-23 was applied.ResultsSixty-two patients were analyzed. The pretreatment FGF-23 levels were related to the iPTH levels, calcium × phosphate product levels, and history of active vitamin D therapy. The pretreatment FGF-23, iPTH, and calcium levels were lower in the patients who would be successfully treated with calcitriol. A logistic regression study revealed that the pretreatment iPTH and FGF-23 levels significantly affected the therapy results. Analyses using a receiver-operated curve revealed that FGF-23 was the best screening test for identifying patients with future refractory response to calcitriol therapy. The treatment would be successful in 88.2% of those with FGF-23 ≤9860 ng/L and iPTH ≤591 pg/mL, while it would be successful in only 4.2% of those with FGF-23 >9860 ng/L and iPTH >591 pg/mL.ConclusionPretreatment serum FGF-23 levels were a good indicator in predicting the response to calcitriol therapy. The measurement of serum FGF-23 levels, especially in combination with iPTH levels, is a promising laboratory examination for the clinical practice of secondary hyperparathyroidism

    The fungal metabolite (+)-terrein abrogates osteoclast differentiation via suppression of the RANKL signaling pathway through NFATc1

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    Pathophysiological bone resorption is commonly associated with periodontal disease and involves the excessive resorption of bone matrix by activated osteoclasts. Receptor activator of nuclear factor (NF)-κB ligand (RANKL) signaling pathways have been proposed as targets for inhibiting osteoclast differentiation and bone resorption. The fungal secondary metabolite (+)-terrein is a natural compound derived from Aspergillus terreus that has previously shown anti-interleukin-6 properties related to inflammatory bone resorption. However, its effects and molecular mechanism of action on osteoclastogenesis and bone resorption remain unclear. In the present study, we showed that 10 µM synthetic (+)-terrein inhibited RANKL-induced osteoclast formation and bone resorption in a dose-dependent manner and without cytotoxicity. RANKL-induced messenger RNA expression of osteoclast-specific markers including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), the master regulator of osteoclastogenesis, cathepsin K, tartrate-resistant acid phosphatase (Trap) was completely inhibited by synthetic (+)-terrein treatment. Furthermore, synthetic (+)-terrein decreased RANKL-induced NFATc1 protein expression. This study revealed that synthetic (+)-terrein attenuated osteoclast formation and bone resorption by mediating RANKL signaling pathways, especially NFATc1, and indicated the potential effect of (+)-terrein on inflammatory bone resorption including periodontal disease

    The Fungal Metabolite (+)-Terrein Abrogates Ovariectomy-Induced Bone Loss and Receptor Activator of Nuclear Factor-kappa B Ligand-Induced Osteoclastogenesis by Suppressing Protein Kinase-C alpha/beta II Phosphorylation

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    Osteoporosis is a common disease characterized by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. Severe bone loss due to osteoporosis triggers pathological fractures and consequently decreases the daily life activity and quality of life. Therefore, prevention of osteoporosis has become an important issue to be addressed. We have reported that the fungal secondary metabolite (+)-terrein (TER), a natural compound derived from Aspergillus terreus, has shown receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast differentiation by suppressing nuclear factor of activated T-cell 1 (NFATc1) expression, a master regulator of osteoclastogenesis. TER has been shown to possess extensive biological and pharmacological benefits; however, its effects on bone metabolism remain unclear. In this study, we investigated the effects of TER on the femoral bone metabolism using a mouse-ovariectomized osteoporosis model (OVX mice) and then on RANKL signal transduction using mouse bone marrow macrophages (mBMMs). In vivo administration of TER significantly improved bone density, bone mass, and trabecular number in OVX mice (p < 0.01). In addition, TER suppressed TRAP and cathepsin-K expression in the tissue sections of OVX mice (p < 0.01). In an in vitro study, TER suppressed RANKL-induced phosphorylation of PKC alpha/beta II, which is involved in the expression of NFATc1 (p < 0.05). The PKC inhibitor, GF109203X, also inhibited RANKL-induced osteoclastogenesis in mBMMs as well as TER. In addition, TER suppressed the expression of osteoclastogenesis-related genes, such as Ocstamp, Dcstamp, Calcr, Atp6v0d2, Oscar, and Itgb3 (p < 0.01). These results provide promising evidence for the potential therapeutic application of TER as a novel treatment compound against osteoporosis

    Exercise habituation is effective for improvement of periodontal disease status: a prospective intervention study

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    Background and purpose: Periodontal disease is closely related to lifestyle-related diseases and obesity. It is widely known that moderate exercise habits lead to improvement in lifestyle-related diseases and obesity. However, little research has been undertaken into how exercise habits affect periodontal disease. The purpose of this study was to examine the effect of exercise habits on periodontal diseases and metabolic pathology.Methods: We conducted a prospective intervention research for 12 weeks. The subjects were 71 obese men who participated in an exercise and/or dietary intervention program. Fifty subjects were assigned to exercise interventions (exercise intervention group) and 21 subjects were assigned to dietary interventions (dietary intervention group). This research was conducted before and after each intervention program.Results: In the exercise intervention group, the number of teeth with a probing pocket depth (PPD) ≥4 mm significantly decreased from 14.4% to 5.6% (P<0.001), and the number of teeth with bleeding on probing (BOP) significantly decreased from 39.8% to 14.4% (P<0.001). The copy counts of Tannerella forsythia and Treponema denticola decreased significantly (P=0.001). A positive correlation was found between the change in the copy count of T. denticola and the number of teeth with PPD ≥4 mm (P=0.003) and the number of teeth with BOP (P=0.010). A positive correlation was also found between the change in the copy count of T. denticola and body weight (P=0.008), low-density lipoprotein cholesterol (P=0.049), and fasting insulin (P=0.041). However, in the dietary intervention group the copy count of T. denticola decreased significantly (P=0.007) and there was no correlation between the number of periodontal disease-causing bacteria and PPD and BOP.Conclusion: Our results are the first to show that exercise might contribute to improvements in periodontal disease

    Syntheses of C17-C27 fragments of 20-deoxybryostatins for assembly using Julia and metathesis reactions

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    Two approaches to the synthesis of compounds corresponding to the C17–C27 fragment of the 20-deoxybryostatins are described.</p
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