Expression and activation of 15-lipoxygenase pathway in severe asthma: relationship to eosinophilic phenotype and collagen deposition

BACKGROUND: Although 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), a product of 15-lipoxygenase (15-LO), may be involved in mild to moderate asthma, little is known about its potential roles in severe asthma. OBJECTIVES: This study was performed to evaluate 15(S)-HETE levels in bronchoalveolar lavage fluid (BALF) from severe asthmatics with and without airway eosinophils and from the control groups. In addition, 15-LO protein expression was examined in endobronchial biopsy, while its expression and activation were evaluated in BAL cells. RESULTS: While 15(S)-HETE levels in BALF were significantly higher in all severe asthmatics than normal subjects, severe asthmatics with airway eosinophils had the highest levels compared with mild, moderate asthmatics and normal subjects. 15(S)-HETE levels were associated with tissue eosinophil numbers, sub-basement membrane thickness and BALF tissue inhibitor of metalloproteinase-1 levels, and were accompanied by increased 15-LO expression in bronchial epithelium. In addition, activation of 15-LO was suggested by the increased proportion of 15-LO in the cytoplasmic membrane of alveolar macrophages from severe asthmatics. CONCLUSION: The data suggest that severe asthmatics with persistent airway eosinophils manifest high levels of 15(S)-HETE in BALF, which may be associated with airway fibrosis. It is likely that 15-LO expression and activation by airway cells explain the increased 15(S)-HETE levels.     

对学习困难学生的施教对策

教师常常偏爱成绩好的学生，而对学习困难学生则在情感上、精力上和研究上投入不够。对学习困难学生的认识往往集中在他们身上的缺陷，而忽视了他们具有的学习潜能。教学实践证明，合理的施教是开发其潜能、促进其转化的关键。     

Therapeutic effect of carbon dioxide laser versus single application of trichloroacetic acid for koilocytic squamous papillae.

This paper reports the treatment results of 50 symptomatic females who had clinical features of squamous papillae and histologic evidence of koilocytosis. Either a carbon dioxide laser or a single application of trichloroacetic acid (TCA) was used to treat these patients. All of the patients were alternately and prospectively randomized into one of two groups. Twenty-three of the 25 women treated by laser and 10 of the 25 women treated by TCA had resolution of either the symptoms or the vulvar lesions in a follow-up period ranging from six to 22 months. Hence, we were able to control the symptoms and lesions in 92% of the women following initial laser treatment and 40% of the women following a single application of TCA. In addition, cosmetic results were satisfactory, and complications were minimal in the laser-treated group of patients. However, human papillomavirus DNA was still detected three to four weeks after treatment in 24% of the women treated by laser and 64% of the women treated by TCA. Whether they are at a higher risk of recurrence as compared to those without detectable viral DNA remains to be determined.     

Additive effects of earthworm extract with HpD-laser on the enhancement of reactive oxygen production and the inhibition of[~3H]—thymidine.uptake in mouse ascitic tumor cells

The effects of combined use of earthworm extract(912)and HpD-laser on the produc-tion of reactive oxygen and the biosynthesis of DNA in S_(180) tumor cells were studied throughchemiluminescence measurement and[~3H]-TdR incorporation assay.The results showed that as com-pared with the control,the intensity of chemiluminescence emitted by tumor cells treatedsimultaneously with 912 and HpD-laser was enhanced more than ten-folds,while that treated with912 or HpD-laser alone was increased only 2～4 folds.The[~3H]-TdR incorporation into tumorcells of the former group was inhibited upto 74.1%,and that of the latter groups decreased onlyby 42.2% and 40.0%,respectively.In accordance with these biochemical changes,the ultrastructuraldamage of tumor cells of the former,combinedly treated group appeared to be the most serious.This suggests an additive effect of 912 with HpD-laser on tumor cells.In addition,if free radicalscavengers,such as catalase and superoxide dismutase,were added to the reaction systembefore chemiluminescence assay,the luminescent enhancement effect mentioned above was dramaticallyalleviated,implying the presence of O_2~ and H_2O_2 in the system.Therefore,as to the toxic effecton tumor cells,912 and HpD-laser are not only additive in efficiency,but also similar in theunderlying mechanism of action.     

Airway challenge test with propranolol

We investigated airway response to propranolol in 48 asthmatics, 17 subjects with chronic bronchitis and 19 normal subjects. The positive rate for propranolol challenge was 93.8% in asthma group, 5.9% in chronic bronchitis group while none in normal group had positive response. The challenge was highly reproducible, and it had few side-effects. This indicated that the challenge was specific and sensitive in diagnosis of asthma, it was a safe, reliable method of measuring non-specific airway responsiveness. Furthermore we also demonstrated that PC20 for propranolol did not relate to PC20 for methacholine, and that the calibre of airway did not significantly influence the airway response to propranolol.     

Randomized placebo-controlled trial comparing montelukast and cetirizine for treating perennial allergic rhinitis in children aged 2–6 yr

Leukotriene receptor antagonists (LTRAs) were recently added to the method of treating allergic rhinitis (AR). However, in children under 6 yr old, there has been no study about its efficacy in treating AR. We aim to compare the clinical efficacy of montelukast, cetirizine and placebo in the treatment of children from 2 to 6 yr old with perennial allergic rhinitis (PAR), to see if there are any significant differences. Sixty children were selected and treated with montelukast, or cetirizine, or placebo once daily. The efficacy of the three agents was compared with the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) and Total Symptom Score (TSS) by diary. In addition, we also examined serum IgE, serum eosinophil cationic protein (ECP), blood eosinophil counts, nasal airway resistance (NAR) and eosinophil percentage in nasal smears. The results revealed that both montelukast and cetirizine were significantly efficacious compared with placebo in NAR, eosinophil percentage in nasal smears, PRQLQ, TSS and all symptom items except nasal itching, throat itching and tearing. For nasal itching, only cetirizine was significantly efficacious. On the other hand, for night sleep quality, montelukast was significantly superior to cetirizine.     

Differential analgesic effect of tenoxicam on post-cesarean uterine cramping pain between primiparous and multiparous women.

BACKGROUND AND PURPOSE: Uterine cramping pain is related to prostaglandins, which are mediated by cyclooxygenase. However, it is unknown whether the analgesic effects of the non-selective cyclooxygenase inhibitor tenoxicam are different between primiparous and multiparous women. This placebo-controlled, double-blind study compared the analgesic effect of tenoxicam on post-cesarean uterine cramping pain in primiparous and multiparous women. METHODS: Forty primiparous women and 40 multiparous women who were scheduled for elective cesarean delivery were allocated into the following 4 groups: saline-primipara (SP) group, tenoxicam-primipara (TP) group, saline-multipara (SM) group, and tenoxicam-multipara (TM) group. Saline or 20 mg tenoxicam was intravenously injected immediately after clamping of the umbilical cord. All patients received patient-controlled analgesia for postoperative pain control. Resting wound pain, uterine cramping pain, morphine consumption, and morphine-related side effects were evaluated at 4 and 24 hours after surgery. RESULTS: At 24 hours after surgery, tenoxicam-related relief of uterine cramping pain was 2.1 in primiparous women (visual analog scale: SP 5.6 (4.4-6.8) minus TP 3.5 (2.2-4.9); p < 0.01). The tenoxicam-related morphine-sparing effect was 14 mg (45%) in primiparous women (SP 31.4 mg (23.9-38.8) minus TP 17.4 mg (11.6-23.2); p < 0.01). The tenoxicam-related relief of uterine cramping pain and tenoxicam-related morphine-sparing effect were not significant in multiparous women. CONCLUSIONS: This study revealed that the analgesic effect of tenoxicam on post-cesarean uterine cramping pain is greater in primiparous women than in multiparous women. Further studies are required to determine whether a higher dosage of tenoxicam is beneficial to reduce uterine cramping pain in multiparous women.