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Abstract: Statins are lipid-lowering agents with pleiotropic effects. We investigated the apoptotic effects of fluvastatin on peripheral CD4+ T cells from healthy subjects. Fluvastatin induced apoptosis in resting CD4+ T cells but not in CD4+ T cells strongly activated with a high concentration of PMA plus ionomycin (PMA/I) analyzed with annexin V and propidium iodide staining. However, CD4+ T cells activated with a low concentration of PMA/I or with anti-CD3 antibodies were apoptotic after treatment with fluvastatin. Activities of caspases-8, -9, and -3 were increased in resting CD4+ T cells treated with fluvastatin (10μM). In strongly activated CD4+ T cells, fluvastatin inhibited the activation of caspase-8 induced by PMA/I and increased caspase-9 activity. The caspase-3 activity did not differ between untreated and fluvastatin-treated strongly activated CD4+ T cells. Treatment with fluvastatin (10μM) enhanced cytochrome c release and increased the Bax/Bcl-2 ratio in both resting and strongly activated CD4+ T cells. Although the in vitro concentration of fluvastatin used in this study is higher than in vivo, other factors may sensitize apoptotic cell death of CD4+ T cells in vivo. In conclusion, fluvastatin induces apoptosis in resting T cells but not in strongly activated T cells, a difference that might be due to the interaction between caspase-8 and caspase-9. [Copyright &y& Elsevier]

Background: Characterization of seafood allergens is important to understand the immune response to these allergens. Moreover, a detailed comparison between atopic and nonatopic patients with adverse reactions to shrimp has never been reported. Methods: Raw and boiled shrimp extracts were analyzed by immunoblotting using sera from 9 atopic and 7 nonatopic patients with a history of adverse reactions to shrimp, and 13 control subjects. Total IgE, specific IgE and skin prick tests (SPT) to shrimp were also investigated. Results: The level of specific IgE to shrimp was higher in atopic patients than nonatopic patients (p < 0.05). Symptoms, SPT results and major allergens involved were similar in atopic and nonatopic patients. The 16.5-kD protein had the highest frequency of IgE binding followed by the 40-kD protein in these patients. Other minor IgE-binding proteins were observed at the 20-, 22-, 54-, 72-, 129- and 140-kD regions. Patients who had binding to the 16.5-kD protein had either positive (25% raw/31% cooked) or negative (13% raw/cooked) CAP-FEIA-RAST, while patients who recognized the 40-kD protein all had positive (31% raw/19% cooked) CAP-FEIA-RAST. All control subjects had negative immunoblots for these two proteins. Conclusion: The 16.5-kD protein was the most frequent protein identified regardless of CAP-FEIA-RAST results, while the 40-kD protein was only present in patients with positive CAP-FEIA-RAST. Therefore, 16.5-kD protein may be an important allergen that is clinically relevant in both atopic and nonatopic patients with adverse reactions to shrimp even if it is not detected by the CAP-FEIA-RAST system. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate the levels of asthma control in Japanese adult patients in general practice., Methods: 11490 Japanese patients with adult asthma who were treated by primary care physicians were enrolled. The treatment steps and levels of asthma control were determined according to the Japanese Asthma Prevention and Management Guideline 2009. In addition, patient satisfaction with asthma management was scored from 0 (dissatisfied) to 10 (fully satisfied)., Results: Inhaled corticosteroids were administered to 90.9% of patients. Of 11490 patients, the percentage of patients undergoing treatment steps 1, 2, 3, and 4 were 41.8%, 31.7%, 28.4%, and 22.1%, respectively. The average scores of satisfaction with asthma treatment in treatment steps 1, 2, 3, and 4 were 7.83, 7.68, 7.62 and 7.46, respectively., Conclusions: Although a large number of patients were treated with inhaled corticosteroids and the rate of satisfaction with asthma management was high in all treatment steps, asthma was poorly controlled in this study. This dissociation was considered to be due to low patient's own goals of asthma treatment.

Background: Although several studies investigate the level of asthma control, real asthma life for patients, factors that influence on patients satisfaction, and reasons for irregular visit have not been studied in Japan., Methods: One thousand and two hundreds patients with adult asthma were studied by internet-based questionnaire from March 25th to 31st in 2009. Satisfaction for asthma management was scored from 0 to 10 and then divided into three groups, such as high (10-8), middle (7-4), and low (3-0) groups. Major questions for these patients were precise explanations on diagnosis of asthma, goal of the treatment, and treatment with medications by the doctors. Furthermore, factors that might have influences on non-adherence and irregular visit by patients were investigated., Results: Severity of the patients enrolled into this study was 34.8% in mild asthma, 19.2% in moderate asthma, and 7.8% in severe asthma. 81.6% of patients were treated with inhaled corticosteroids or combination of inhaled corticosteroid and long acting inhaled beta(2)-agonist. The average score for satisfaction of patients was 6.83 and satisfaction of patients was 43.2% in high, 48.9% in middle, and 7.9% in low group. Patients with low satisfaction group had not been precisely explained the diagnosis of asthma, goal of the treatment, and treatment with medications by the doctors. Less non-adherence and low number of irregular visits were observed in patients with high satisfaction group., Conclusion: Although this study was performed by internet-based questionnaire and might not reflect the real management of asthma in Japan, the lower the satisfaction, the less patients received explanations on the diagnosis of asthma, goal of the treatment, and treatment with medications by the doctors. Therefore, explanations for these factors may have great influences on non-adherence and irregular visits in patients with asthma.

Background: In asthmatic patients, first asthmatic symptoms are not often typical. In those cases, it takes long time before asthma diagnosis, and the severities are progressed in some patients. For early intervention, we tried to make the diagnostic criteria for asthma, which are useful to diagnose as early stage of asthma., Methods: Three hundred and eighty eight of asthmatic patients, who were recorded first their symptoms in asthma, were enrolled. Their first symptoms and examinations were analyzed., Results: In first asthmatic symptoms, 79% of patients had cough, 68% patients had wheezing, 49% patients had dyspnoea, and 15% of patients did not have typical asthmatic symptoms in the early stage. The percentages of abnormal in first examinations were 99% in airway hypersensitivity, 92% of low %V25, 82% of eosinophila in sputum and 77% of low %V50. Low FEV1% and reversible airway obstruction were not seen in a lot of patients., Conclusion: We advocate that the diagnostic criteria for early stage of asthma are the following three elements. First criterion is spasmodic cough, wheezing and dyspnoea. Second criterion is airway hypersensitivity, or over 3% of eosinophils in sputum, or under 70% of %V50, or under 50% of %V25, or effect of bronchodilator. Effect of bronchodilator will be required, when the symptom is cough only. Third criterion is the exclusion of other lung and heart diseases.

Obstructive sleep apnoea (OSA) and type 2 diabetes frequently co-exist and potentially interact haemodynamically and metabolically. However, the confounding effects of obesity have obscured the examination of any independent or interactive effects of the hypoxic stress of OSA and the hyperglycaemia of type 2 diabetes on haemodynamic and metabolic outcomes. We have developed a chronically catheterized, unhandled, lean murine model to examine the effects of intermittent hypoxic (IH) exposure and exogenous glucose infusion on the diurnal pattern of arterial blood pressure and blood glucose, as well as pancreatic beta-cell growth and function. Four experimental groups of adult male C57BL/J mice were exposed to 80 h of (1) either IH (nadir of inspired oxygen 5-6% at 60 cycles h(-1) for 12 h during light period) or intermittent air (IA; control) and (2) continuous infusion of either 50% dextrose or saline (control). IH exposure during saline infusion caused a sustained increase in arterial blood pressure of 10 mmHg (P < 0.0001), reversed the normal diurnal rhythm of blood glucose (P < 0.03), doubled corticosterone levels (P < 0.0001), and increased replication of pancreatic beta-cells from 1.5 +/- 0.3 to 4.0 +/- 0.8% bromodeoxyuridine (BrdU)-positive) beta-cells. The combined stimulus of IH exposure and glucose infusion attenuated the hypertension, exacerbated the reversed diurnal glucose rhythm, and produced the highest rates of apoptosis in beta-cells, without any additive effects on beta-cell replication. We conclude that, in contrast to the development of sustained hypertension, IH impaired glucose homeostasis only during periods of hypoxic exposure. IH acted as a stimulus to pancreatic beta-cell replication, but the presence of hyperglycaemia may increase the hypoxic susceptibility of beta-cells. This model will provide a basis for future mechanistic studies as well as assessing the metabolic impact of common comorbities in OSA, including obesity, insulin resistance and type 2 diabetes.