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Inhibition of mast cell tryptase by inhaled APC 366 attenuates allergen-induced late-phase airway obstruction in asthma 总被引:7,自引:0,他引:7
Krishna MT Chauhan A Little L Sampson K Hawksworth R Mant T Djukanovic R Lee T Holgate S 《The Journal of allergy and clinical immunology》2001,107(6):1039-1045
BACKGROUND: APC 366, a selective inhibitor of mast cell tryptase, has been shown to inhibit antigen-induced early asthmatic response (EAR), late asthmatic response (LAR), and bronchial hyperresponsiveness (BHR) in a sheep model of allergic asthma. OBJECTIVE: The purpose of this study was to investigate the effects of APC 366 on antigen-induced EAR, LAR, and BHR in mild atopic asthmatics not on any anti-inflammatory therapy. METHODS: Sixteen mild atopic asthmatics, each with a demonstrable antigen-induced EAR, LAR, and BHR to histamine, were recruited into this randomized, double-blinded, crossover study. APC 366 (5 mg)/placebo was administered by aerosol inhalation 3 times per day on treatment days 1 through 4. Allergen challenge was carried out on day 4. Histamine challenge was performed the following morning, 1 hour after final dosing. RESULTS: Subjects were shown to have a significantly smaller overall mean area under the curve for the LAR (P =.012) and mean maximum fall in FEV(1) for the LAR (P =.007) after pretreatment with APC 366 in comparison with placebo. No significant effects on BHR were demonstrable. Although the EAR was reduced by 18% after treatment with APC 366 in comparison with placebo, this was not statistically significant. CONCLUSION: Short-term repeated administration of APC 366 significantly reduced the magnitude of antigen-induced LAR in atopic asthmatics, which supports the role of mast cell tryptase in the pathophysiology of the LAR. 相似文献
53.
Ljubica?Mandic Denise?Traxler Alfred?Gugerell Katrin?Zlabinger Dominika?Lukovic Noemi?Pavo Georg?Goliasch Andreas?Spannbauer Johannes?Winkler Mariann?Gy?ngy?siEmail author 《Current cardiovascular imaging reports》2016,9(10):27
Purpose of Review
Myocardial infarction (MI) leading to heart failure displays an important cause of death worldwide. Adequate restoration of blood flow to prevent this transition is a crucial factor to improve long-term morbidity and mortality. Novel regenerative therapies have been thoroughly investigated within the past decades.Recent Findings
Increased angiogenesis in infarcted myocardium has shown beneficial effects on the prognosis of MI; therefore, the proangiogenic capacity of currently tested treatments is of specific interest. Molecular imaging to visualize formation of new blood vessels in vivo displays a promising option to monitor proangiogenic effects of regenerative substances.Summary
Based on encouraging results in preclinical models, molecular angiogenesis imaging has recently been applied in a small set of patients. This article reviews recent literature on noninvasive in vivo molecular imaging of angiogenesis after MI as an integral part of cardiac regeneration.54.
Analysis of the third‐ and fourth‐generation cephalosporin use for the treatment of infections caused by Gram‐negative bacteria in hospital settings 下载免费PDF全文
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Kašnar-Šamprec J Ratkaj I Mišković K Pavlak M Baus-Lončar M Kraljević Pavelić S Glavaš-Obrovac L Žinić B 《Investigational new drugs》2012,30(3):981-990
New N-1-sulfonylpyrimidines showed potent growth inhibitory activity against human and mouse tumour cells of different origin. 1-(p-toluenesulfonyl)cytosine (TsC) and 1-(p-toluenesulfonyl)cytosine hydrochloride (TsC × HCl) inhibited the growth of human cervical carcinoma cells (HeLa), and had no significant cytotoxic effects on normal human foreskin fibroblasts (BJ). TsC and TsC × HCl interfered with the HeLa cell cycle progression bringing about the accumulation of G1 phase cells and the induction of apoptosis. Antiproliferative effects of TsC and TsC × HCl were additionally confirmed by investigating de novo synthesis of RNA, DNA and proteins in HeLa cells. Monitoring gene expression using DNA Chip Analysis and quantitative PCR showed that TsC × HCl affects the expression of several cell-cycle regulating genes implying that cell cycle arrest and DNA damage-induced apoptosis might account for the observed cellular effects. In vivo experiments revealed low toxicity of TsC × HCl, as demonstrated by unaltered haematological and metabolic blood parameters. In conclusion, potent antitumour efficacy and low toxicity of new compounds in comparison with the common chemotherapy drug 5-FU make them promising anticancer agents. Additional pre-clinical and clinical studies are warranted to illuminate the mode of action of these newly synthesized compounds in vivo, which would lay the groundwork for their further optimization. 相似文献
56.
Association between viral infections and post-transplant malignancies in renal transplant recipients
Basić-Jukić N Bubić-Filipi L Lovcić V Ratković I Petar K 《Acta medica Croatica : c?asopis Hravatske akademije medicinskih znanosti》2011,65(4):355-359
Immunosuppressive treatment is associated with an increased incidence of different malignant diseases. The etiology of posttransplant malignancies is multifactorial and includes decreased immune response to different viral infections, inappropriate removal of damaged cells, and impaired ability to repair DNA. EBV, HHV-8, Merkel cell virus, hepatitis B virus, hepatitis C virus and BK virus are all considered to be involved in the etiology of post-transplant malignancies. CMV has been considered as a potential causative factor in the development of colon cancer. However, current knowledge is mainly based on case reports. Further studies are needed to establish the causative role of different viruses in the etiology and pathogenesis of different malignant diseases in renal transplant population. 相似文献
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Vlak T Kaštelan D Lozo P Aljinović J Gradišer M Mijić S Nikolić T Miškić B Car D Tajšić G Dušek T Jajić Z Grubišić F Poljičanin T Bakula M Džubur F Strižak-Ujević M Kadojić M Radman M Vugrinec M Kuster Z Pekez M Radović E Labar L Crnčević-Orlić Z Koršić M 《Clinical rheumatology》2011,30(12):1549-1554
A prospective, open-labelled, multicentre 6-month study was designed to assess three categories that have high impact on Health-Related Quality of Life (HR-QoL). These categories were: satisfaction, preference and drug tolerability in postmenopausal patients with osteoporosis in Croatia, at first treated with weekly oral bisphosphonates, followed by monthly oral ibandronate. Three hundred eighty-five postmenopausal women who were treated with one of the weekly bisphosphonates for at least 6?months were included into the study and after they had signed written informed consent, the therapy was changed to monthly ibandronate. Satisfaction with the treatment was assessed with the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q). Patients completed OPSAT-Q at the baseline visit before the change of therapy (visit 1) and 6?months after the change of therapy (visit 2). Following 6?months ibandronate therapy, the values in all four domains of the OPSAT-Q (convenience, confidence with daily activities, overall satisfaction, side effects) as well as in the Composite Satisfaction Score were higher in visit 2 (p?0.001). Values in subjects enrolled into the patient assistance programme did not differ significantly from the values in subjects that were not (p?=?0.399) except for the domain convenience (p?=?0.026). This study demonstrates significantly higher satisfaction in patients who switched from the weekly bisphosphonate therapy regimen to monthly ibandronate in all observed aspects of treatment. Patients expressed preference for monthly bisphosphonate (ibandronate) in comparison with weekly bisphosphonates and found it to be a more convenient method of treatment. At the time of study, however, it was not known that the anti-fracture effect of ibandronate was smaller for hip fractures than with other bisphosphonates. 相似文献
59.