Suppression of nitric oxide production from nasal fibroblasts by metabolized clarithromycin in vitro

<p>Abstract</p> <p>Background</p> <p>Low-dose and long-term administration of 14-membered macrolide antibiotics, so called macrolide therapy, has been reported to favorably modify the clinical conditions of chronic airway diseases. Since there is growing evidence that macrolide antibiotic-resistant bacteria's spreaders in the populations received macrolide therapy, it is strongly desired to develop macrolide antibiotics, which showed only anti-inflammatory action. The present study was designed to examine the influence of clarithromycin (CAM) and its metabolized materials, M-1, M-4 and M-5, on free radical generation from nasal polyp fibroblasts (NPFs) through the choice of nitric oxide (NO), which is one of important effector molecule in the development of airway inflammatory disease <it>in vitro</it>.</p> <p>Methods</p> <p>NPFs (5 × 10⁵cells/ml) were stimulated with 1.0 μg/ml lipopolysaccharide (LPS) in the presence of agents for 24 hours. NO levels in culture supernatants were examined by the Griess method. We also examined the influence of agents on the phosphorylation of MAPKs, NF-κB activation, iNOS mRNA expression and iNOS production in NPFs cultured for 2, 4, 8, and 12 hours, respectively.</p> <p>Results</p> <p>The addition of CAM (> 0.4 μg/ml) and M-4 (> 0.04 μg/ml) could suppress NO production from NPFs after LPS stimulation through the suppression of iNOS mRNA expression and NF-κB activation. CAM and M-4 also suppressed phosphorylation of MAPKs, ERK and p38 MAPK, but not JNK, which are increased LPS stimulation. On the other hand, M-1 and M-5 could not inhibit the NO generation, even when 0.1 μg/ml of the agent was added to cell cultures.</p> <p>Conclusion</p> <p>The present results may suggest that M-4 will be a good candidate for the agent in the treatment of chronic airway inflammatory diseases, since M-4 did not have antimicribiological effects on gram positive and negative bacteria.</p

The Effectiveness of Simultaneous Combination Therapy Using S-1 and Nedaplatin with Radiation for Five Cases of Maxillary Cancer

In our department, we provide treatment for malignant head and neck tumors with the goal of preserving organs and function. We report the treatment outcomes for five patients with maxillary cancer who underwent S-1 and nedaplatin treatment with concurrent radiation therapy (SN therapy) in our department from April 2005 to March 2009. The patients included one case classified as T2N0M0 and four cases classified as T4N0M0. All patients were male and were aged between 29 and 67 years with a mean age of 55.6 years. Among the five cases, four achieved cancer-free survival with preservation of all functions after undergoing treatment. In the remaining case, the tumor did not disappear but was locally controlled via superselective arterial injection and CyberKnife treatment; however, pulmonary metastasis occurred and the patient is surviving with cancer. SN therapy has allowed a reduction in the extent of surgery required and the preservation of organs and function. It will be necessary to study an increased number of cases in the future to determine the survival rate and the effectiveness of organ and function preservation in maxillary cancer patients after SN therapy

Functional tooth number and mortality

Aim: Previous studies on the association between intraoral conditions and mortality in community-dwelling older individuals reported that fewer present teeth (PT) are significant risk factors for mortality. However, how the number of PT relative to the number of functional teeth (FT), including both present and rehabilitated teeth, influences mortality has not been investigated fully. This study examined the impact of the number of FT on mortality among community-dwelling Japanese older adults. Methods: This study was a retrospective, observational and population-based follow-up study, which examined 1188 older individuals who participated in an annual geriatric health examination from 2009 to 2015. The average follow-up period was 1697.0 ± 774.5 days. The primary outcome was all-cause mortality at follow-up. The numbers of PT and FT of each participant were counted during an oral examination. In addition, demographics, clinical variables, blood nutrient markers, physical functions and perceived masticatory function were measured. Results: Kaplan–Meier analysis, followed by a log-rank test, revealed that fewer PT (P < 0.001) and FT (P = 0.002) were significantly associated with a reduced survival rate. Cox's proportional hazard analysis indicated that the number of FT, but not the number of PT, was a significant independent mortality risk factor after adjusting for demographics, clinical variables, nutrient markers and physical functioning (P = 0.036, hazard ratio: 2.089). Conclusions: Current results suggest that the number of FT more strongly predicts all-cause mortality than the number of PT among community-dwelling older adults. Further studies are necessary to consider the confounding of socioeconomic status and disability status

Number of functional teeth more strongly predicts all‐cause mortality than number of present teeth in Japanese older adults

Aim Previous studies on the association between intraoral conditions and mortality in community‐dwelling older individuals reported that fewer present teeth (PT) are significant risk factors for mortality. However, how the number of PT relative to the number of functional teeth (FT), including both present and rehabilitated teeth, influences mortality has not been investigated fully. This study examined the impact of the number of FT on mortality among community‐dwelling Japanese older adults. Methods This study was a retrospective, observational and population‐based follow‐up study, which examined 1188 older individuals who participated in an annual geriatric health examination from 2009 to 2015. The average follow‐up period was 1697.0 ± 774.5 days. The primary outcome was all‐cause mortality at follow‐up. The numbers of PT and FT of each participant were counted during an oral examination. In addition, demographics, clinical variables, blood nutrient markers, physical functions and perceived masticatory function were measured. Results Kaplan–Meier analysis, followed by a log‐rank test, revealed that fewer PT (P  Conclusions Current results suggest that the number of FT more strongly predicts all‐cause mortality than the number of PT among community‐dwelling older adults. Further studies are necessary to consider the confounding of socioeconomic status and disability status

Impact of number of functional teeth on independence of Japanese older adults

Aim To examine the relationship between the number of present and functional teeth at baseline and future incidence of loss of independence. Methods Participants were community-dwelling older individuals who participated in a comprehensive geriatric health examination conducted in Kusatsu town, Japan, between 2009 and 2015. The primary endpoint was the incidence of loss of independence among participants, defined as the first certification of long-term care insurance in Japan. The numbers of present and functional teeth at baseline were determined via an oral examination. Demographics, clinical variables (e.g., history of chronic diseases and psychosocial factors), blood nutritional markers, physical functions, and perceived masticatory function were assessed. Results This study included 1121 individuals, and 205 individuals suffered from loss of independence during the follow-up period. Kaplan–Meier estimates of loss of independence for participants with smaller numbers of present and functional teeth were significantly greater than for those with larger numbers of teeth. Cox proportional hazard analyses indicated that a smaller number of present teeth was not a significant risk factor after adjusting for demographic characteristics. However, the number of functional teeth was a significant risk factor after the adjustment (hazard ratio: 1.975 [1.168–3.340]). Additionally, higher hazard ratios were observed in other adjusted models, but they were not statistically significant. Conclusions The number of functional teeth may be more closely related to the future incidence of loss of independence than the number of present teeth. This novel finding suggests that prosthodontic rehabilitation for tooth loss possibly prevents the future incidence of this life-event

On the origin and evolution of the asteroid Ryugu: A comprehensive geochemical perspective

Presented here are the observations and interpretations from a comprehensive analysis of 16 representative particles returned from the C-type asteroid Ryugu by the Hayabusa2 mission. On average Ryugu particles consist of 50% phyllosilicate matrix, 41% porosity and 9% minor phases, including organic matter. The abundances of 70 elements from the particles are in close agreement with those of CI chondrites. Bulk Ryugu particles show higher δ18O, Δ17O, and ε54Cr values than CI chondrites. As such, Ryugu sampled the most primitive and least-thermally processed protosolar nebula reservoirs. Such a finding is consistent with multi-scale H-C-N isotopic compositions that are compatible with an origin for Ryugu organic matter within both the protosolar nebula and the interstellar medium. The analytical data obtained here, suggests that complex soluble organic matter formed during aqueous alteration on the Ryugu progenitor planetesimal (several 10’s of km), <2.6 Myr after CAI formation. Subsequently, the Ryugu progenitor planetesimal was fragmented and evolved into the current asteroid Ryugu through sublimation

A pristine record of outer Solar System materials from asteroid Ryugu’s returned sample

Volatile and organic-rich C-type asteroids may have been one of the main sources of Earth’s water. Our best insight into their chemistry is currently provided by carbonaceous chondritic meteorites, but the meteorite record is biased: only the strongest types survive atmospheric entry and are then modified by interaction with the terrestrial environment. Here we present the results of a detailed bulk and microanalytical study of pristine Ryugu particles, brought to Earth by the Hayabusa2 spacecraft. Ryugu particles display a close compositional match with the chemically unfractionated, but aqueously altered, CI (Ivuna-type) chondrites, which are widely used as a proxy for the bulk Solar System composition. The sample shows an intricate spatial relationship between aliphatic-rich organics and phyllosilicates and indicates maximum temperatures of ~30 °C during aqueous alteration. We find that heavy hydrogen and nitrogen abundances are consistent with an outer Solar System origin. Ryugu particles are the most uncontaminated and unfractionated extraterrestrial materials studied so far, and provide the best available match to the bulk Solar System composition

A dehydrated space-weathered skin cloaking the hydrated interior of Ryugu

Without a protective atmosphere, space-exposed surfaces of airless Solar System bodies gradually experience an alteration in composition, structure and optical properties through a collective process called space weathering. The return of samples from near-Earth asteroid (162173) Ryugu by Hayabusa2 provides the first opportunity for laboratory study of space-weathering signatures on the most abundant type of inner solar system body: a C-type asteroid, composed of materials largely unchanged since the formation of the Solar System. Weathered Ryugu grains show areas of surface amorphization and partial melting of phyllosilicates, in which reduction from Fe3+ to Fe2+ and dehydration developed. Space weathering probably contributed to dehydration by dehydroxylation of Ryugu surface phyllosilicates that had already lost interlayer water molecules and to weakening of the 2.7 µm hydroxyl (–OH) band in reflectance spectra. For C-type asteroids in general, this indicates that a weak 2.7 µm band can signify space-weathering-induced surface dehydration, rather than bulk volatile loss