Crude Extracts of Caenorhabditis elegans Suppress Airway Inflammation in a Murine Model of Allergic Asthma

Epidemiological studies suggest an inverse relationship between helminth infections and allergic disease, and several helminth-derived products have been shown to suppress allergic responses in animals. This study was undertaken to evaluate the effect of a crude extract of Caenorhabditis elegans on allergic airway inflammation in a murine model of asthma. Allergic airway inflammation was induced in BALB/c mice by sensitization with ovalbumin. The effect of the C. elegans crude extract on the development of asthma and on established asthma was evaluated by analyzing airway hyperresponsiveness, serum antibody titers, lung histology and cell counts and cytokine levels in the bronchoalveolar lavage fluid. The role of IFN-γ in the suppression of asthma by the C. elegans crude extract was investigated in IFN-γ knockout and wild-type mice. When mice were sensitized with ovalbumin together with the crude extract of C. elegans, cellular infiltration into the lung was dramatically reduced in comparison with the ovalbumin-treated group. Treatment of mice with the C. elegans crude extract significantly decreased methacholine-induced airway hyperresponsiveness and the total cell counts and levels of IL-4, IL-5 and IL-13 in the bronchoalveolar lavage fluid but increased the levels of IFN-γ and IL-12. Sensitization with the C. elegans crude extract significantly diminished the IgE and IgG1 responses but provoked elevated IgG2a levels. However, the suppressive effect of the C. elegans crude extract was abolished in IFN-γ knockout mice, and the Th2 responses in these mice were as strong as those in wild-type mice sensitized with ovalbumin. The crude extract of C. elegans also suppressed the airway inflammation associated with established asthma. This study provides new insights into immune modulation by the C. elegans crude extract, which suppressed airway inflammation in mice not only during the development of asthma but also after its establishment by skewing allergen-induced Th2 responses to Th1 responses

Multi-Dimensional Limiting Process for Two- and Three- Dimensional Flow Physics Analysis

In this paper, we derive a limiting condition for three-dimensional compressible flows and present the multi-dimensional limiting process for three-dimensions. The basic idea of the multi-dimensional limiting condition is that the vertex values interpolated at a grid point should be within the maximum and minimum cell-average values of neighboring cells for the monotonic distribution. By applying the MLP (Multi-dimensional Limiting Process), we can achieve monotonic characteristic, which results in the substantial enhancement of solution accuracy and convergence behavior

Importance of remission and residual somatic symptoms in health-related quality of life among outpatients with major depressive disorder: a cross-sectional study

Background: Major depressive disorder (MDD) is strongly associated with an impaired quality of life (QoL), which is itself affected by various factors. Symptom-oriented ratings poorly reflect the impact of disease on the QoL and level of functioning of the mental health of subjects. The purpose of this study was to assess health-related QoL (HRQoL) using preference-based measures in outpatients with MDD with regard to their remission achievement and clinical factors affecting the HRQoL. Methods: This was a cross-sectional observational study. We recruited 811 patients with MDD from 14 psychiatric outpatient clinics in Korea. They were divided into three groups as follows: a new visit group (n = 287), a remitted group (n = 235), and a non-remitted group (n = 289). The 17-item Hamilton Depression Rating Scale was used to assign patients to the remitted or non-remitted group. The general HRQoL was assessed with the EuroQol 5D (EQ-5D), using both the EQ-5D index score and the EuroQol Visual Analog Scale (EQ-VAS). The disease-specific HRQoL was assessed with the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Results: The non-remitted group showed a significant impairment of HRQoL in view of the subscales of EQ-5D index scores, EQ-VAS, and Q-LES-Q-SF. The EQ-5D index score in the remitted group was 0.77 ± 0.10, while it was 0.57 ± 0.23 in the non-remitted group and 0.58 ± 0.24 in the new visit group (p < 0.0001). The EQ-VAS scores for the remitted and non-remitted groups were 72.5 ± 16.6 and 50.9 ± 20.3, respectively (p < 0.0001). Likewise, patients with remission had the Q-LES-Q-SF total score of 46.5 ± 8.8, whereas those with non-remission reported 36.7 ± 7.7 (p < 0.0001). The symptom severity measured by the Depression and Somatic Symptoms Scale was significantly correlated with the HRQoL. Furthermore, patients with severe somatic symptoms showed a significantly lower EQ-5D index score (0.54 ± 0.24) than those with mild/moderate somatic symptoms (0.75 ± 0.12; p = 0.002). Conclusion: Non-remitted MDD patients, especially those with more severe somatic symptoms, show a distinct impairment of HRQoL and more clinical symptoms, suggesting the importance of achieving remission in the treatment of MDD

Intravenous Vitamin C administration reduces fatigue in office workers: a double-blind randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Studies of the efficacy of vitamin C treatment for fatigue have yielded inconsistent results. One of the reasons for this inconsistency could be the difference in delivery routes. Therefore, we planned a clinical trial with intravenous vitamin C administration.</p> <p>Methods</p> <p>We evaluated the effect of intravenous vitamin C on fatigue in office workers. A group of 141 healthy volunteers, aged 20 to 49 years participated in this randomized, double-blind, controlled clinical trial. The trial group received 10 grams of vitamin C with normal saline intravenously, while the placebo group received normal saline only. Since vitamin C is a well-known antioxidant, oxidative stress was measured. Fatigue score, oxidative stress, and plasma vitamin C levels were measured before intervention, and again two hours and one day after intervention. Adverse events were monitored.</p> <p>Results</p> <p>The fatigue scores measured at two hours after intervention and one day after intervention were significantly different between the two groups (p = 0.004); fatigue scores decreased in the vitamin C group after two hours and remained lower for one day. Trial also led to higher plasma vitamin C levels and lower oxidative stress compared to the placebo group (p < 0.001, p < 0.001, respectively). When data analysis was refined by dividing each group into high-baseline and low-baseline subgroups, it was observed that fatigue was reduced in the lower baseline vitamin C level group after two hours and after one day (p = 0.004). The same did not hold for the higher baseline group (p = 0.206).</p> <p>Conclusion</p> <p>Thus, intravenous vitamin C reduced fatigue at two hours, and the effect persisted for one day. There were no significant differences in adverse events between two groups. High dose intravenous vitamin C proved to be safe and effective against fatigue in this study.</p> <p>Trial Registration</p> <p>The clinical trial registration of this trial is <url>http://ClinicalTrials.gov</url><a href="http://www.clinicaltrials.gov/ct2/show/NCT00633581">NCT00633581</a>.</p

Quality of Life in Patients with Osteoporotic Vertebral Fractures

Study DesignA case-control study.PurposeTo examine several dimensions of health-related quality of life (HRQL) in postmenopausal women with osteoporotic vertebral fractures, compared with a control group.Overview of LiteratureOsteoporotic vertebral fractures are a major cause of morbidity among postmenopausal women. There have been many reports of a decrease in the quality of life in patients with osteoporotic vertebral fractures. However,few reports have analyzed which dimensions contribute to the decline in quality of life.MethodsOne thousand five hundred forty-five postmenopausal women aged 50 years and older from 17 study sites in nationwide hospitals were in enrolled in the study (between April 2008 and January 2009). HRQL was measured using the European Quality of Life 5 Domains (EQ-5D), and visual analogue scale (VAS).ResultsThe average VAS of the case group was 57.80, and that of the control group was 64.10 (p=0.001). All domains of the EQ-5D score were significantly worse in the case group (p=0.001). Among the case group, the average VAS of the 559 patients (45%) who were operated on was 56.8, and that of the remaining 680 patients (55%) who were treated conservatively was 58.6 (p=0.135). Among the case group, the averages of each EQ-5D domain of the 559 patients (45%) who were operated on were: 1.87 in mobility, 1.81 in self-care, 1.99 in usual activities, 2.11 in pain, and 1.62 in anxiety or depression. Those of the 680 patients (55%) who were treated conservatively were: 1.72 in mobility, 1.60 in self-care, 1.76 in usual activities, 1.98 in pain, and 1.57 in anxiety or depression. Except for the domain of anxiety or depression, scores for the other domains were all significantly worse in the patients who were operated on (p=0.001).ConclusionsHealth related quality of life in the patients with osteoporotic vertebral fractures was significantly worse in both the EQ-5D domains and VAS. Among the osteoporotic vertebral fracture patients, the patients who were operated on had a worse quality of life in EQ-5D

The bent conformation of poly(A)-binding protein induced by RNA-binding is required for its translational activation function

A recent study revealed that poly(A)-binding protein (PABP) bound to poly(A) RNA exhibits a sharply bent configuration at the linker region between RNA-recognition motif 2 (RRM2) and RRM3, whereas free PABP exhibits a highly flexible linear configuration. However, the physiological role of the bent structure of mRNA-bound PABP remains unknown. We investigated a role of the bent structure of PABP by constructing a PABP variant that fails to form the poly(A)-dependent bent structure but maintains its poly (A)-binding activity. We found that the bent structure of PABP/poly(A) complex is required for PABP&apos;s efficient interaction with eIF4G and eIF4G/eIF4E complex. Moreover, the mutant PABP had compromised translation activation function and failed to augment the formation of 80S translation initiation complex in an in vitro translation system. These results suggest that the bent conformation of PABP, which is induced by the interaction with 30 poly(A) tail, mediates poly(A)-dependent translation by facilitating the interaction with eIF4G and the eIF4G/eIF4E complex. The preferential binding of the eIF4G/eIF4E complex to the bent PABP/poly(A) complex seems to be a mechanism discriminating the mRNA-bound PABPs participating in translation from the idling mRNA-unbound PABPs.111Ysciescopu