Functional Mechanism Underlying COX-2 Expression Following Administration of Indomethacin in Rat Stomachs: Importance of Gastric Hypermotility

The expression of COX-2 is up-regulated in the rat stomach after administration of indomethacin, and the inhibition of this enzyme may be a key to NSAID-induced gastric damage. The present study investigated the mechanism for COX-2 expression induced in the rat stomach by indomethacin, in relation with the ulcerogenic processes. The animals were given indomethacin or SC-560 p.o., and the gastric mucosa was examined 8 hr later. Indomethacin decreased the mucosal PGE2 content and produced gross damage with gastric hypermotility and the expression of COX-2 mRNA in the mucosa. Although SC-560 did not produce damage, this agent caused a decrease in the PGE2 content and an increase in gastric motility as well as the up-regulation of COX-2 expression, and provoked damage in the presence of rofecoxib. Gastric lesions induced by indomethacin were prevented by both atropine (even in the presence of exogenous HCl) and omeprazole, although the hypermotility response was inhibited only by atropine. The COX-2 expression induced by indomethacin or SC-560 was inhibited by atropine, even in the presence of exogenous HCl, while omeprazole had no effect. The mucosal PGE2 content was decreased by SC-560 at 2 hr but recovered 8 hr later, and this recovery of PGE2 was attenuated by both atropine and rofecoxib but not omeprazole. These results suggested that the COX-2 expression in the stomach following treatment with indomethacin is functionally associated with gastric hypermotility response induced by COX-1 inhibition. Luminal acid does not play a role in the up-regulation of COX-2 expression in the stomach following administration of indomethacin.     

Adverse effects and adherence to nasal continuous positive airway pressure in patients with obstructive sleep apnea hypopnea syndrome]

The adverse effects of and adherence of a treatment with nasal continuous positive airway pressure (nCPAP) for obstructive sleep apnea and hypopnea syndrome (OSAHS) were examined. The subjects comprised 321 patients with OSAHS. An all-night polysomnography was performed for all subjects. Titration of CPAP was performed manually. Regarding the adverse effects of nCPAP therapy, the subjects most frequently complained of nasal symptoms, air-leaks and any trouble with the mask. Complaints heard less frequently were sleep disturbances, dry pharyngeal and oral cavities, noises, and pronounced pressure sensations due to CPAP. No adverse effects were noted in 13% of the subjects. The adherence was as high as 73.0% in 122 patients in whom time spent for nCPAP treatment could be analyzed. The mean treatment time was 4.7 +/- 1.8 hours. We found no significant correlation between mean treatment time and age, BMI, ESS, CPAP, AHI, Ar-I, ODI, lowest SpO 2, or %TST with SpO 2 < 90%. Multivariate analysis revealed no factor significantly correlated with treatment time. These results showed that detailed instructions for the prevention of adverse effects may improve the adherence of CPAP.     

Sex differences in early mortality of patients undergoing primary stenting for acute myocardial infarction.

BACKGROUND: Limited information exists regarding the impact of gender on in-hospital outcome after primary stenting for acute myocardial infarction (AMI). METHODS AND RESULTS: A total of 2,981 patients (790 women and 2,191 men) participated in the study who were admitted within 24 h after symptom onset and underwent emergency primary stenting for AMI. Compared with men, women were significantly older; had higher incidences of hypertension, diabetes mellitus, hyperlipidemia, Killip class > or =2, and cardiogenic shock; had a higher blood glucose level and a lower serum creatinine level on admission. Other baseline characteristics, including the incidences of ST-segment elevation AMI, anterior infarction, 3-vessel disease, initial or final Thrombolysis in Myocardial Infarction (TIMI) flow grade did not significantly differ between the sexes. The in-hospital mortality rate was significantly higher in women than in men (9.4% vs 5.2%, p<0.001). On multivariate analysis, age, Killip class, blood glucose level, serum creatinine level, and final TIMI grade were independent predictors of in-hospital death, but female gender was not (odds ratio 1.01, p=0.69). CONCLUSIONS: Our findings suggest that in patients undergoing primary stenting for AMI, women have higher in-hospital mortality than men, but female gender itself is not independently associated with increased in-hospital mortality after adjustment for baseline differences.     

Long-term outcome after mitral valve replacement with preservation of continuity between the mitral annulus and the papillary muscle in patients with mitral stenosis

BACKGROUND AND AIM OF THE STUDY: The effect on left ventricular performance of mitral valve replacement (MVR) with preservation of continuity between the mitral annulus and papillary muscle was studied in patients with mitral stenosis (MS). METHODS: Forty patients with MS who underwent MVR between 1986 and 1995 and had long-term echocardiographic follow up were studied retrospectively. Eighteen patients had conventional MVR (CMVR group), and 22 (PMVR group) had either preservation of autologous chordae tendineae (n = 6) or replacement of the chordae with expanded polytetrafluoroethylene sutures (n = 16). RESULTS: Preoperatively, there were no significant differences between the two groups in age, body surface area, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), fractional shortening (FS) or ejection fraction (EF). At 3.1-6.5 years after surgery, periodic echocardiography showed significant differences (p <0.05) in LVESD (35.8 versus 31.6 mm, respectively, in the CMVR and PMVR groups) and FS (31.8% versus 38.1%). At 6.6-9.7 years postoperatively, no significant differences were observed between the two groups in FS, but LVESD was significantly greater in the CMVR group than in the PMVR group (37.3 versus 31.5 mm). CONCLUSION: In the long term, MVR with preservation of continuity between the mitral annulus and papillary muscle improves systolic left ventricular performance in patients with MS.     

Increased expression of interleukin-10 in unstable plaque obtained by directional coronary atherectomy.

AIMS: The present study investigates the expression and localization of interleukin (IL)-10, an important anti-inflammatory cytokine, in atherectomy specimens from patients with stable and unstable angina. METHODS AND RESULTS: Twenty-two patients with stable angina and 21 with unstable angina who underwent directional coronary atherectomy for de novo lesions were studied. The atherectomy specimens were morphologically assessed and immunohistochemically stained with antibodies for IL-10, macrophages, smooth muscle cells, and endothelial cells. The localization and immunopositive areas were evaluated using an image analysing system. Immunoreactivity for IL-10 was detected in coronary plaques, especially in macrophages. Immunopositive areas of macrophages and IL-10, as well as the incidence of thrombus formation, were significantly greater in specimens from patients with unstable angina than in those from patients with stable angina (macrophages, P<0.001; IL-10, P<0.05; thrombus formation, P<0.05; respectively). Even after adjustment, IL-10 expression and the incidence of thrombus formation were significantly greater in the unstable angina group (P<0.05, each). The immunoreactivities for smooth muscle cells and endothelial cells did not differ between the two groups. CONCLUSION: IL-10 was more frequently expressed in specimens from patients with unstable angina. This finding might contribute to a better understanding of plaque instability.     

Outbreak of hepatitis C virus infection in an outpatient clinic

BACKGROUND: From January through September 2001, seven patients were admitted to Fukaya Red Cross Hospital with typical clinical manifestations of acute hepatitis. Six were outpatients of the clinic, which is located near the hospital. An extensive survey of clinic outpatients conducted by the local health department revealed six more new acute hepatitis cases during this period. METHODS: A case control study was carried out to identify potential risk factors for infection. In total, 1946 outpatients with clinic records were scheduled to undergo hepatitis C virus (HCV)-antibody testing. For the HCV-Ab positive patients, HCV-RNA was subtyped and quantified, and sequences of HCV hypervariable region 1 were determined. RESULTS: Ultimately, 12 patients with acute hepatitis and two asymptomatic subjects were found to be a part of this outbreak. HCV isolates were divided into three major groups using phylogenetic tree analysis. Only a past history of visiting the clinic was significantly associated with acute hepatitis. The timing of the parenteral medical procedure at the clinic and the onset of acute hepatitis strongly suggested association of the two events. CONCLUSIONS: Our findings suggest that nosocomial HCV infection can occur in an outpatient clinic, even in countries where post-transfusion hepatitis has been almost entirely eliminated.     

Induction of differentiation of pre-NKT cells to mature Vα14 NKT cells by granulocyte/macrophage colony-stimulating factor

Valpha14 NKT cells express an invariant antigen receptor encoded by Valpha14 and Jalpha281 gene segments as well as natural killer (NK) markers, including NK1.1. Here, we describe a precursor population of NKT cells (pre-NKT) that expresses NK1.1, T cell antigen receptor beta, pTalpha, and RAG1/2 but not Valpha14 and surface CD3epsilon. Such pre-NKT cells were differentiated successfully in vitro into mature CD3epsilon+ Valpha14(+) NKT cells by IL-15 and granulocyte/macrophage colony-stimulating factor (GM-CSF) in conjunction with stroma cells. Interestingly, only GM-CSF without stroma cells induced the Valpha14-Jalpha281 gene rearrangement in the pre-NKT cells. This also was confirmed by the findings that the number of mature Valpha14 NKT cells and the frequency of Valpha14-Jalpha281 rearrangements were decreased significantly in the mice lacking a GM-CSF receptor component, common beta-chain. These results suggest a crucial role of GM-CSF in the development of Valpha14 NKT cells in vivo.     

Kimura’s disease (angiolymphoid hyperplasia with eosinophilia) associated with ulcerative colitis

We treated a 35-year-old Japanese woman who had Kimura’s disease associated with ulcerative colitis. Kimura’s disease is an uncommon chronic inflammatory disease considered to be of allergic origin based on the presence of eosinophilia and IgE hyperimmunoglobulinemia, and may be a manifestation of a systemic immunologic disturbance. Some immunological complications such as nephrotic syndrome have been reported in association with Kimura’s disease, but the present case is the first associated with ulcerative colitis.     

Autoantibody profiles and their association with blood eosinophils in asthma and COPD

Background

Autoimmune involvement in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD) has been proposed, and autoantibodies are a hallmark of autoimmunity. This study aimed to compare the autoantibody profiles of asthma and COPD, and the relationship between autoantibodies and features of these diseases.

Impact of anti-doping education and doping control experience on anti-doping knowledge in Japanese university athletes: a cross-sectional study

Background

This study was conducted to elucidate the anti-doping (AD) education, doping control experience, and AD knowledge according to the World Anti-doping Code (Code) of Japanese university athletes.

Methods

We collected data from 514 male athletes (M_age?=?19.53 years, SD?=?1.13) and 629 female athletes (M_age?=?20.99 years, SD?=?1.07). We asked them about their experience undergoing doping control and the AD education they had received. Then, we assessed their AD knowledge using the World Anti-Doping Agency’s Athlete Learning Program about Health and AD (ALPHA) test.

Results

The results showed that 2.54% of the participants had undergone doping control. Further, 30.10% received AD education at least once, and 20.82% received AD education more than once. When comparing the ALPHA scores of athletes with/without doping test experience, we observed no significant difference. However, the ALPHA scores of athletes with/without AD education were significantly different; specifically, athletes who received AD education more than once had significantly higher ALPHA scores than non-educated athletes.

Conclusion

These results revealed that doping control experience was not related to AD knowledge and that AD education was associated with AD knowledge, suggesting that athletes who receive AD education more than once have more accurate AD knowledge than less educated athletes on this topic. The importance of AD education in promoting understanding of AD according to the Code in sports is highlighted in this study.