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61.

Background

Transmembrane protein 16A (TMEM16A) is associated with mucus secretion and ion transport in asthma. Clarithromycin (CAM) is reported to inhibit IL-13-induced goblet cell metaplasia. However, the effect of CAM on TMEM16A function and expression remains unclear.

Methods

Tracheal epithelial cells from guinea pigs were cultured for ~14 days at an air-liquid interface in medium containing IL-13 (10?ng/ml) in the absence or presence of CAM (20?µg/ml) or a TMEM16A inhibitor, T16Ainh-A01 (10 µg/ml). Electrophysiological studies were performed by Ussing?s short-circuit technique. The cells were used for immunofluorescence staining with antibodies against TMEM16A, MUC5AC, and α-tubulin. The cells were also examined by transmission electron microscopy. TMEM16A protein levels in the cell lysates were determined by ELISA. For the in vivo study, guinea pigs were treated intratracheally with IL-13 in the absence or presence of CAM or T16Ainh-A01.

Results

CAM decreased the MUC5AC-positive cells and reduced TMEM16A expression in them and increased the α-tubulin-positive cells. CAM inhibited TMEM16A protein levels in a dose-dependent manner, and decreased UTP-induced Cl ion transport. In cells treated with IL-13 for 24?h, TMEM16A appeared prior to MUC5AC protein expression, and was inhibited by CAM. In the in vivo study, CAM inhibited IL-13-induced goblet cell metaplasia and TMEM16A expression. The inhibitory effects of CAM were similar to those of T16Ainh-A01.

Conclusions

CAM inhibited IL-13-induced TMEM16A expression, Cl ion transport and goblet cell metaplasia both in vitro and in vivo. CAM may thus improve airway mucociliary differentiation by attenuating TMEM16A expression in IL-13-related asthma.  相似文献   
62.
目的:评价克拉霉素对反复喘息急性加重期患儿鼻咽灌洗液中TNF-α、IL-1β和IL-10的影响。方法:将54例反复喘息急性加重期患儿为研究对象,分别给予克拉霉素与安慰剂治疗,并于治疗过程中检测患儿鼻咽灌抽吸物中TNF-α、IL-1β和IL-10含量的变化情况。结果:与安慰剂相比,克拉霉素治疗3~5天后鼻咽抽吸物中TNF-α和IL-1β显著降低(P<0.05);治疗3~8周后TNF-α、IL-1β和IL-10水平均有不同程度降低,但肺炎嗜衣原体和肺炎支原体感染患儿IL-10水平无明显影响。结论:克拉霉素能降低喘息急性加重期患儿粘膜中TNF-α、IL-1β和IL-10的浓度。  相似文献   
63.
70例幽门螺杆菌(Hp)感染的消化性溃疡或功能性消化不良患者随机分成A、B两组,接受7天抗Hp三联治疗。A组的治疗方案为:洛赛克20mg、克拉霉素250mg和呋喃唑酮100mg,一日二次:B组的方案为:洛赛克20mg、克拉霉素250mg和甲硝唑400mg,一日二次:A、B组中分别有1例和2例失访。结果显示,A、B组的Hp根除率分别为88.2%(30/34)和78.8%(26/33)(P=0.297):治疗前Hp菌株对克拉霉素和甲硝唑的耐药率分别为5.9%(4/67)和37.7%(25/67):克拉霉素耐药4例的Hp均未得到根除:B组中对甲硝唑耐药者的Hp根除率为66.6%(8/12),而敏感者的根除率为85.7%(18/21)(P=0.198);A、B组中消化性溃疡的愈合率分别为93.3%(14/15)和85.7%(12/14)(P=0.501);两组中各2例有轻度的副反应。Hp菌株对克拉霉素、甲硝唑耐约是影响上述低剂量、短疗程方案疗效的重要因素。A组三联疗法的Hp根除率高于B组,可作为第一或第二线方案应用。  相似文献   
64.
目的观察奥美拉唑、克拉霉素、阿莫西林三联疗法治疗肝源性溃疡的疗效。方法经胃镜确诊的肝源性溃疡患者58例,随机分为治疗组(31例)和对照组(27例)。两组患者均给予综合治疗。治疗组患者给予奥美拉唑20mg,口服,2次/d;克拉霉素500mg,口服,2次/d;阿莫西林1000mg,口服,2次/d。对照组单用奥美拉唑20mg,口服,2次/d。十二指肠溃疡治疗2周,胃溃疡治疗3周。疗程结束后,用内窥镜观察溃疡愈合情况。结果治疗组和对照组溃疡愈合率分别为87.0%和55.5%,差异有统计学意义(P<0.01);治疗后6个月和12个月,治疗组溃疡复发率分别为14.8%和18.5%,对照组分别为33.3%和40.0%,差异均有统计学意义(P<0.01)。结论奥美拉唑、克拉霉素、阿莫西林三联疗法治疗肝源性溃疡临床效果显著。  相似文献   
65.
88例幽门螺杆菌(Hp)感染的卜:指肠溃疡(DU)和功能性消化不良患耆分两期研究.接受7天克拉霉素合并的j联治疗。I期乃预研究,28例随饥分婀组接受电托堪索500mg、呋喃畔刚200mg合}}I}变体次枸橼酸铋(CBS)240mg(A组)或、!索托哗30mg(B组)。¨?次治疗。60例进入ll;《Ij研究符心分AfllB同组.药物配合方棠M I期.似除CBS外.接他药物刊毓i或、{i l、I】彬j—IJ舒BlJ仃4例科】1例Iq约物驯f互『-?术。t限:i^_j’.火i方2例i^泶!Il!_,Ji.I垮jA、BiH f10H1)根除半分SIj为100~;i,(12,12)f1 J91.6‘%(11 12):Il㈣A,B纠i n0Hp橄除?}行}jl_乃92 6‘j;,(25,一’27)和90.0%(27,30)备组问的Hp撤除?爷无!It并蓐别(P>0.0j)。I、ll期·l,削J三J-t j幸j,,别乃64.2,}2,(18j28)和Ij】”i(3/58)(P<0.001)。lI期A、B两组的DU愈合率分别为94.4%(17/18)和100%(18/18)。lJ期r}·的两种低制m地程j联{j’}J、地较乃圳魁的Hp橄除玎案.7.5%(4/j3)的Hp曲株则电十£。《豢味发耐药.足i青,j:欠帔的{:嘤味N  相似文献   
66.
A 74-year-old woman was referred to our department because of epigastralgia. Endoscopic findings revealed yellowish bumpy mucosa from the bulbus to the second portion of the duodenum. The patient was admitted to our hospital for further examinations and treatment for this lesion. Endoscopic mucosal resection (EMR) was performed on part of the lesion to obtain the final diagnosis, and then mucosa-associated lymphoid tissue (MALT) lymphoma of the duodenum was diagnosed using this procedure. In this case, no evidence of Helicobacter pylori infection in the patient's stomach was detected by any of the diagnostic examinations used, such as the urea breath test, histological study, culture, and serological antibody. For this reason, the patient's duodenal MALT lymphoma was treated solely with long-term clarithromycin, which had an inhibitory action on lymphocyte activation. The lesion showed slight improved during the first 12 days of treatment, and complete regression was reached after 6 months of treatment. It is suggested that the long-term use of clarithromycin may be effective for diseases of the gastrointestinal tract associated with the lymphocyte proliferation.  相似文献   
67.
Conventional triple therapies for Helicobacter pylori (H. pylori ) eradication have recently shown a disappointing reduction in effectiveness in many countries. The main reason for failure was found to be bacterial resistance to one of the most commonly used antibiotics, clarithromycin. An additional problem for conventional triple therapy is the high rate of resistance to metronidazole found in Europe, America and Asia. In Italy, in the last 15 years a 2-fold increase in resistance has occurred. A recent study of the whole of Italy included about 20 patients from each region at the first endoscopic diagnosis of H. pylori infection. The most surprising result was the patchy distribution of resistance, which was almost absent in two regions (one northern and one southern), although the highest prevalence was found in some regions of the South. In the paediatricpopulation we found a 25% prevalence of resistance in a sample of H. pylori positive children observed between 2002 and 2007, mirroring data obtained in southern European countries. Clarithromycin resistance assessment is currently based on phenotypic detection performed after culture the agar dilution method or E-test, and genotypic methods based on polymerase chain reaction (PCR). In a recent comparative study we found a 71.2% agreement between the two methods. Culture-free techniques are highly accurate in finding even minimal traces of genotypically resistant strains. Moreover, PCR-based tools are accurate in detecting a heteroresistant status, defined as the co-existence of some strains that are susceptible and some resistant to the same antibiotic in an individual patient. Three point mutations, namely A2143G , A2142G and A2142C , are responsible for 90% of cases of primary clarithromycin resistance in H. pylori strains isolated in Western countries, although we previously demonstrated that the presence of the A2143G mutation, but not A2142G or A2142C , significantly lowered the H. pylori eradication rate. Treatment failure has considerable cost/benefit implications because of "waste" of National Health System and patient resources, in terms of drugs, further diagnostic tests and medical examination expenses. Therefore, in future it would be very useful to be able to test for clarithromycin resistance before starting conventional triple therapy. Hopefully, fast, effective noninvasive tests may soon be devised to determine this condition.  相似文献   
68.
美宝胃肠胶囊对HP感染性胃肠黏膜病变的疗效观察   总被引:1,自引:1,他引:0  
目的:观察美宝胃肠胶囊治疗HP感染性胃肠黏膜病变病人在根除HP方面的疗效。方法:临床上将具有上消化道症状的病人,经内镜检查证实为消化性溃疡、慢性浅表-萎缩性胃炎伴(或不伴)糜烂,病理检查排除胃癌,内镜下取活组织做快速尿素酶检测HP均阳性病人为本研究入选病例;治疗前均未经过正规的抗HP治疗;将入选病例随机分为A、B两组,两组病人均应用奥美拉唑20mg口服2次/日,治疗一周;A组病人均使用美宝胃肠胶囊,B组为常规治疗药物,用药四周后停药,停药4周后复查胃镜及HP检测。结果:A组中HP转阴者17例,根除率为85%;B组中HP转阴者18例,根除率为90%。两组之间无显著性差异。结论:美宝胃肠胶囊对溃疡及胃炎病人HP的根除有明显的临床疗效,其效果与药物治疗组相似。  相似文献   
69.
Prolonged release microparticles of clarithromycin (CL) were prepared using Eudragit RL 100 and RS 100 by spray-drying and casting-drying techniques. For the characterization of those microparticles, preparation yield, particle size distribution, X-ray diffraction, thermal behavior, active agent content and in vitro dissolution from the microparticles were performed. HPLC was used for the assay of clarithromycin and the assay method was validated. All the formulations obtained showed prolonged release when compared to pure clarithromycin. Microparticles prepared by spray-drying method had a slower release compared to those of casting-drying method. Spray-drying method seems to be a more suitable method to prepare microparticles for prolongation in release.  相似文献   
70.
There is increasing evidence of Helicobacter pylori (H. pylori) resistance to the classical triple therapy consisting of a proton-pump inhibitor and clarithromycin with either amoxicillin or metronidazole. This study is aimed at establishing the efficacy and safety of a 14-day regimen to eradicate H. pylori in patients who have failed with the classical triple therapy given for 14 days. One hundred seventy-six patients diagnosed to have H. pylori infection were given triple therapy for 14 days. Fifty-two patients who failed to respond as evident from positive 14C-urea breath test (UBT) done 4–6 weeks after the completion of triple therapy were offered a combination regimen comprised of furazolidone 200 mg b.i.d, co-amoxiclav 1 g b.i.d., colloidal bismuth subcitrate 240 mg b.i.d., and esomeprazole 40 mg b.i.d. for 14 days. The mean age of these patients was 41 ± 13 years (range 20–67). Thirty-four were males. To document eradication of H. pylori, UBT was repeated 4 weeks after the completion of treatment. On an intention-to-treat analysis, the eradication rate was 81% (42 out of 52) whereas on per-protocol basis, the eradication rate was 82.4% (42 out of 51). In conclusion, this new regimen represents a suitable second-line therapy. This study was conducted under ClinicalTrials.gov number NCT00520949.  相似文献   
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