培养幽门螺杆菌-小鼠适应株的实验研究

目的培养幽门螺杆菌-小鼠适应株.方法 (1)先用4株cagA及vacA基因,均为阳性菌株的H.pylori给10只BALB/c小鼠灌胃,4周后剖杀,取小鼠胃黏膜培养及鉴定后得两株(小1、小2)H.pylori-小鼠适应株;(2)用细菌学检查观察小鼠的H.pylori定植情况.结果用4株cagA及vacA基因阳性菌株去感染小鼠,有三只感染成功,感染率为33.3%(3/9),两只传代成功.H.pylori感染小鼠胃黏膜H.pylori定植多位于胃小凹上部及胃腺腔内,数量不多.结论 cagA及vacA基因均为阳性的云南菌株,灌胃后能定植在BALB/c小鼠胃内,培养出H.pylori-小鼠适应株.     

尿苷二磷酸葡聚糖转移酶1A8*2在云南健康佤族、白族和藏族基因多态性研究

目的:了解云南佤族、白族和藏族人群中尿苷二磷酸葡聚糖转移酶1A8*2的基因多态性,并与其他种族比较,了解种族差异。方法:使用聚合酶链反应-限制性片段长度多态性的方法对云南144名佤族、115名白族和252名藏族健康个体进行尿苷二磷酸葡聚糖转移酶1A8*2基因分型。计算各民族基因型频率,并检验是否符合Hardy-Weinberg平衡。用χ2检验比较佤族、白族和藏族人群以及已报道的其他民族的基因型频率和等位基因频率。结果:云南佤、白、藏三族健康人群尿苷二磷酸葡聚糖转移酶1A8*2基因频率与文献报道的其他种族比较结果表明,佤族健康人群CC、CG、GG基因型频率分别为16.7%、52.8%和30.5%,白族分别为35.7%、50.4%和13.9%,藏族的分别为8.3%、78.2%和13.5%。佤族、白族和藏族尿苷二磷酸葡聚糖转移酶1A8*2 G等位基因频率分别为56.9%、39.1%和52.6%,与非洲裔美国人及德国高加索人比较其突变率明显增高;白族与日本人比较突变率增高,但突变率低于汉族;云南白族尿苷二磷酸葡聚糖转移酶1A8*2 G等位基因频率与佤族和藏族均有统计学差异(P<0.01),但佤族和藏族之间无差异。上述所有基因型分布比例都符合Hardy-Weinberg平衡。结论:云南佤族、白族和藏族尿苷二磷酸葡聚糖转移酶1A8*2的突变发生情况均有自己的特点,在临床应用相关药物时,进行这些位点基因型检测,将有助于指导临床个体化用药。     

幽门螺杆菌蛋白芯片检测CagA、VacA在儿童相关疾病中的临床价值

目的 探讨幽门螺杆菌(Helicobacter pylori,H.pylori)细胞毒素相关蛋白A(Cytotoxinassociated A,CagA)、空泡毒素A(Vac lating cytotoxin A,VacA)在儿童上消化道疾病(Gastrointestinal disorders,GD)和免疫性血小板减少性紫癜(Idiopathic Thrombocytopenic Purpura,ITP)中的临床价值.方法 选择2019年1月至2019年12月就诊于江西省儿童医院GD患儿436例,其中44例消化性溃疡(Gastroduodenal ulcer,GU),98例胃炎(Chronic superficial gastritis,CSG),294例功能性消化不良组(functional dyspepsia,FD),ITP患儿138例和健康体检儿童104例,采用蛋白芯片检测各组H.pylori CagA、VacA及实验室检测指标.结果 GD组H.pylori检出率为59.86％,GD组Ⅰ型H.pylori感染率53.64％高于Ⅱ型H.pylori感染率43.29％(χ2=5.592,P=0.018).ITP组H.pylori检出率为52.89％,ITP组Ⅱ型H.pylori感染率为54.79％与Ⅰ型H.pylori菌株感染率42.47％差异无统计学意义(χ2=2.221,P=0.136).GU组CagA+高于CSG组(χ2=4.219,P=0.041)和FD组(χ2=48.723,P=0.000);CSG组CagA+显著高于FD组(χ2=36.233,P=0.000)和NC组(χ2=68.866,P=0.000);FD组CagA+高于NC组(χ2=22.387,P=0.000).GU组和CSG组以Ⅰ型菌株为主.FD组以Ⅱ型菌株为主,高于Ⅰ型菌株感染率(P<0.05).I型H.pylori感染ITP患儿CD4+T(％)、CD4+T/CD8+T低于Ⅱ型ITP患儿CD4+T(％)、CD4+T/CD8+T,差异具有统计学意义(P均<0.05),I型H.pylori感染ITP患儿CD8+T(％)显著高于Ⅱ型ITP患儿CD8+T(％)(P<0.05).I型H.pylori感染ITP患儿血清炎症指标IL-6水平显著高于Ⅱ型(t=2.167,P=0.034).结论 I型H.pylori菌株比II型H.pylori菌株毒力更强,可导致更为严重的上消化道疾病;ITP与H.pylori感染具有相关性,I型H.pylori感染ITP患儿免疫细胞功能受损更严重,体内炎症反应更剧烈.     

幽门螺杆菌蛋白芯片检测CagA、VacA在儿童相关疾病中的临床价值

目的 探讨幽门螺杆菌(Helicobacter pylori,H.pylori)细胞毒素相关蛋白A(Cytotoxinassociated A,CagA)、空泡毒素A(Vac lating cytotoxin A,VacA)在儿童上消化道疾病(Gastrointestinal disorders,GD)和免疫性血小板减少性紫癜(Idiopathic Thrombocytopenic Purpura,ITP)中的临床价值.方法 选择2019年1月至2019年12月就诊于江西省儿童医院GD患儿436例,其中44例消化性溃疡(Gastroduodenal ulcer,GU),98例胃炎(Chronic superficial gastritis,CSG),294例功能性消化不良组(functional dyspepsia,FD),ITP患儿138例和健康体检儿童104例,采用蛋白芯片检测各组H.pylori CagA、VacA及实验室检测指标.结果 GD组H.pylori检出率为59.86％,GD组Ⅰ型H.pylori感染率53.64％高于Ⅱ型H.pylori感染率43.29％(χ2=5.592,P=0.018).ITP组H.pylori检出率为52.89％,ITP组Ⅱ型H.pylori感染率为54.79％与Ⅰ型H.pylori菌株感染率42.47％差异无统计学意义(χ2=2.221,P=0.136).GU组CagA+高于CSG组(χ2=4.219,P=0.041)和FD组(χ2=48.723,P=0.000);CSG组CagA+显著高于FD组(χ2=36.233,P=0.000)和NC组(χ2=68.866,P=0.000);FD组CagA+高于NC组(χ2=22.387,P=0.000).GU组和CSG组以Ⅰ型菌株为主.FD组以Ⅱ型菌株为主,高于Ⅰ型菌株感染率(P<0.05).I型H.pylori感染ITP患儿CD4+T(％)、CD4+T/CD8+T低于Ⅱ型ITP患儿CD4+T(％)、CD4+T/CD8+T,差异具有统计学意义(P均<0.05),I型H.pylori感染ITP患儿CD8+T(％)显著高于Ⅱ型ITP患儿CD8+T(％)(P<0.05).I型H.pylori感染ITP患儿血清炎症指标IL-6水平显著高于Ⅱ型(t=2.167,P=0.034).结论 I型H.pylori菌株比II型H.pylori菌株毒力更强,可导致更为严重的上消化道疾病;ITP与H.pylori感染具有相关性,I型H.pylori感染ITP患儿免疫细胞功能受损更严重,体内炎症反应更剧烈.     

幽门螺杆菌感染与儿童哮喘发病的相关性分析

目的 探讨幽门螺杆菌(H.pylori)感染与哮喘发病的影响,分析H.pylori感染对免疫功能指标、辅助性T细胞1(Th1)/辅助性T细胞2(Th2)和辅助性T细胞17(Th17)/调节T细胞(Treg)平衡的影响。方法 收集2020年1月至2021年12月,在南阳市第一人民医院接受治疗的哮喘病儿(哮喘组)142例,及健康儿童(对照组)120例。采用14C呼气试验检测H.pylori感染情况,比较哮喘组和对照组中H.pylori阳性率。哮喘病儿根据是否合并H.pylori感染,分为H.pylori阴性组和H.pylori阳性组,比较两组间免疫功能指标、Th1/Th2及Th17/Treg。结果 哮喘组H.pylori阳性率10.6%显著低于对照组32.5%(χ²=19.13,P<0.001)。轻度哮喘组、中度哮喘组和重度哮喘组H.pylori阳性率分别为22.2%(10/45)、6.6%(4/61)和2.8%(1/36),三组间比较均差异有统计学意义(χ²=9.82,P=0.007),且重度哮喘组H.pylori阳性率低于轻度哮喘组(χ...     

胃良恶性病变中幽门螺杆菌感染与端粒酶的关系

目的　探讨胃良恶性病变组织中端粒酶表达情况及其与幽门螺杆菌 (H .pylori)感染的关系。 方法　采用端粒酶TRAP ELISA方法检测 1 9例慢性浅表性胃炎 (CSG)、2 9例胃癌 (GC)、69例胃良性溃疡(GU)组织端粒酶活性 ,并分析三组H .pylori感染与端粒酶表达的关系。 结果　CSG、GU、GC三组端粒酶阳性表达率分别为 0 %、36 2 % (2 5/ 69)和 79 3 % (2 3/ 2 9)。其中GU组中无伴肠上皮化生及异型增生的 2 5例组织中端粒酶阳性率为 8% (2 / 2 5) ;GU伴肠上皮化生的为 40 % (6/ 1 5) ;GU伴异型增生的为 58 6 % (1 7/ 2 9)。CSG组与GC组及GU组比较、GU组与GC组比较 χ2 =2 4 6～ 9 6 ,P <0 0 1 ;GU无伴肠上皮化生及异型增生的与GU伴有肠上皮化生及异型增生的比较 χ2 =1 5 2 ,P <0 0 1 ;GU伴肠上皮化生的与GU伴异型增生的比较 χ2 =1 1 ,P >0 0 5。CSG、GU和GC组H .pylori感染率分别为 31 6 %、65 3 %和 44 8% ,CSG组与GC组比较、GU组与GC组比较差异无显著意义 (P >0 0 5) ;CSG组与GU组比较差异有显著意义 (χ2 =6 91 ,P<0 0 1 ) ,各组中H .pylori阳性组端粒酶阳性表达率与H .pylori阴性组端粒酶阳性表达率间比较差异均无显著意义 (P均 >0 0 5)。结论　端粒酶激活是胃癌发生的早期事件 ,但可能与H .pylori     

内蒙古地区蒙汉族儿童正常人群HLA-DRB1基因多态性研究

目的 研究内蒙古地区蒙、汉族儿童正常人群HLA-DRB1等位基因的分布概况。方法 采用分析性研究策略，引入PCR-SSP技术，对祖籍三代居住内蒙古地区，无血缘关系和与异族通婚史的蒙、汉族正常健康儿童102名和108名进行HLA-DRB1等位基因的型别分析和比较。结果 (1)蒙、汉族HLA-DRBl各等位基因均被检出；(2)蒙古族HLA-DRB1基因频率较高的依次是*040x(14．9％)、*120x(13．7％)和*150x(10．3％)，而较低的等位基因依次是：*1001(2％)、*160x(2％)和*010x(3．5％)；汉族HLA．DRBl基因频率较高的等位基因依次是：*090l(15％)、*150x(13．4％)和*040x(11．8％)，而较低的等位基因依次是：*1001(3．8％)、*070x(4．2％)和*160x(4．2％)；(3)蒙古族HLA-DRB1*070x和*120x基因频率分别为9．2％和13．7％，高于汉族相应的4．2％和5．7％(χ^2分别是4．061和7．318，P分别是0．044和0．007)，差异有统计学意义。而汉族DRB1*0901基因频率为15％，高于蒙古族4．5％(χ^2=12．462，P=0．000)，差异有非常显著意义；(4)蒙、汉族间遗传距离(D)为0．253。结论 内蒙古地区蒙、汉族儿童健康人群中HLA-DRB1等位基因分布不同，但差异不大，符合中华民族是一个统一整体这一事实。     

中国汉族和回族药物代谢酶细胞色素P450(CYP)3A4、CYP2C9、CYP2C19及CYP2D6基因多态性分析

目的对中国汉族、回族健康人群细胞色素P450(CYP)3A4、CYP2C9、CYP2C19及CYP2D6进行基因多态性分析,比较汉族和回族健康人群基因表型和基因频率分布。方法多聚酶链反应-限制性片段长度多态性(PCR-RFLP)法,对300名志愿者的几种基因进行分型。结果汉族、回族CYP3A4*5等位基因频率均为0,CYP3A4*18等位基因频率分别为0.18,0.19;汉族、回族CYP2C9*2等位基因频率分别为0.01,0.05;CYP2C9*13等位基因频率均为0;汉族、回族CYP2C19*2等位基因频率分别为0.39,0.50;CYP2C19*3等位基因频率分别为0.05,0.05;汉族、回族CYP2D6*10等位基因频率分别为0.57,0.39。结论汉族、回族健康人群的CYP3A4*18、CYP2C9*2、CYP2C19*2、CYP2C19*3均没有显著性差异;在汉族、回族健康人群中未发现CYP3A4*5和CYP2C9*13突变;汉族、回族CYP2D6*10等位基因频率有显著性差异(P<0.01);回族人群CYP2D6中速代谢型(*10/*10)频率为13.4%,明显低于汉族的33.1%(P<0.01)。     

新生儿6 698例常见遗传性聋基因筛查结果分析

目的 分析南宁地区新生儿常见耳聋基因携带情况和突变类型,探讨汉族与壮族之间的差异。方法 采用导流杂交技术对2017年8月至2021年4月在广西壮族自治区民族医院出生的6 698例新生儿进行GJB2、SLC26A4、mt DNA和GJB3基因的13个突变位点检测,分析耳聋基因的总体检出率及突变位点的分布情况,对壮汉两民族进行统计分析。结果 耳聋基因筛查总阳性119例,总体检出率为1.78%,汉族为2.02%,壮族为1.63%,差异无统计学意义（P=0.253）。GJB2基因为主要突变基因,总体检出率为1.00%,汉族1.11%,壮族1.00%,两者差异无统计学意义（P=0.680）。其次是SLC26A4基因0.48%,mt DNA0.27%和GJB3 0.03%,在汉族与壮族间差异无统计学意义（P>0.05）。c.235 del C是主要突变位点,检出率为0.875%,在汉族与壮族间差异无统计学意义（P>0.05）。SLC26A4基因的c.919-2A>G突变位点的检出率汉族高于壮族,差异有统计学意义（P=0.028）。结论 GJB2基因为新生儿常见耳聋主要突变基因;汉...     

小儿幽门螺杆菌阳性伴十二指肠溃疡的药物治疗研究

目的 评价不同药物治疗方案的疗效,观察幽门螺杆菌(H.pylori)根除与溃疡愈合、胃炎好转的关系,进一步探讨H.pylori与十二指肠溃疡的关系.方法 将90例H.pylori阳性的十二指肠溃疡患儿随机分为3组:1组(30例):雷尼替丁3 mg·kg-1·d-1×8周 羟氨苄青霉素50 mg·kg-1·d-1×4周;2组(30例):雷尼替丁3 mg·kg-1·d-1×8周 羟氨苄青霉素50 mg·kg-1·d-1×4周 次枸橼酸铋钾(CBS)6 mg·kg-1·d-1×6周;3组(30例):奥美拉唑10 mg×2周 羟氨苄青霉素50 mg·kg-1·d-1×4周.停药4周后复查.结果 3组溃疡愈合率分别为16.7%、46.7%、93.3%;H.pylori转阴率分别为40.0%、66.7%、100%;胃炎好转率分别为26.7%、36.7%、86.7%.H.pylori转阴者溃疡愈合率67.7%,H.pylori未转阴者28例溃疡愈合5例,差异有显著性(P＜0.05).以铋剂治疗者血铋浓度9.04～18.12 μg/L.结论 H.pylori的存在影响溃疡的愈合.奥关拉唑 羟氨苄青霉素"二联"疗法治疗H.pylori阳性十二指肠溃疡在溃疡愈合、H.pylori根除、胃炎好转方面均有较好疗效,疗程短、副作用小、顺应性好.     

Helicobacter pylori strains and histologically-related lesions affect the outcome of triple eradication therapy: a study from southern Italy

BACKGROUND: Certain evidence suggests that Helicobacter pylori strains expressing genes for cytotoxin production show a higher sensitivity than non-cytotoxic organisms to eradication treatment. No data are available on the involvement of bacterium-related lesions in different therapeutic outcomes. AIMS: (i) To investigate whether differences in eradication rates may be related to the different expression of virulent strains (cagA, vacA, iceA) in patients undergoing proton pump inhibitor-based triple therapy, and (ii) to evaluate whether therapeutic outcome may be affected by bacterium-induced gastric lesions. METHODS: One hundred and ten H. pylori-positive subjects were enrolled. H. pylori was genotyped by polymerase chain reaction. Treatment consisted of lansoprazole-amoxicillin-clarithromycin, twice daily for 1 week. Eradication was checked by urea breath test. RESULTS: The eradication rate was 70%, and the absence of cagA was associated with unsuccessful treatment. No difference between the groups with successful and unsuccessful eradication was found with regard to vacA and iceA. Lympho-epithelial lesions and fibrosis were associated with unsuccessful treatment. CONCLUSIONS: The present data confirm the importance of cagA (but not vacA and iceA) as a predictor of successful eradication. When fibrosis and lympho-epithelial lesions are present, therapy appears to be less effective. Therefore, these histological features may be involved in an unsuccessful therapeutic outcome.     

Helicobacter pylori effects on gastritis, gastrin and enterochromaffin-like cells in Zollinger-Ellison syndrome and non-Zollinger-Ellison syndrome acid hypersecretors treated long-term with lansoprazole

BACKGROUND: Helicobacter pylori is said to cause atrophy of the gastric corpus and enterochromaffin-like cell proliferation in gastro-oesophageal reflux disease (GERD) patients treated long-term with a proton pump inhibitor. AIMS: To determine the effect of H. pylori infection on gastritis, enterochromaffin-like cell density and hyperplasia, mucosal atrophy and serum gastrin in patients with gastric hypersecretion (basal acid output gt; 15 mmol/h) with either hypergastrinemia (Zollinger-Ellison syndrome) or normal gastrin (non-Zollinger-Ellison syndrome) before and during long-term treatment with lansoprazole. METHODS: Lansoprazole was individually titrated to reduce basal acid output to < 5 mmol/h (< 1 mmol/h in post-surgical Zollinger-Ellison syndrome). Gastric corpus biopsies were obtained every 6 months before treatment and up to 8 years later. RESULTS: H. pylori was present in corpus biopsies in approximately 50%, causing active gastritis which resolved rapidly in 15 subjects after elimination of H. pylori. Patchy mild/moderate corpus atrophy was present at entry in two and at the end in four out of 60 patients, one being H. pylori-positive. Intestinal metaplasia (< 10%) was seen in six isolated biopsies (1% of total). H. pylori did not affect serum gastrin, enterochromaffin-like cell density or hyperplasia. Enterochromaffin-like cell density was twice as high in Zollinger-Ellison syndrome as in non-Zollinger-Ellison syndrome patients (241 vs. 126 cells/mm2, P < 0.001). Enterochromaffin-like cells remained normal in the non-Zollinger-Ellison syndrome hypersecretors regardless of H. pylori status. CONCLUSION: Corpus enterochromaffin-like cell increases were related to serum gastrin elevation, but neither H. pylori nor long-term treatment with lansoprazole alone or together had any effect on enterochromaffin-like cell density or hyperplasia. Corpus acute gastritis resulted from H. pylori infection, but did not result in mucosal atrophy despite long-term proton pump inhibitor treatment and promptly resolved with loss of H. pylori.     

Induction of cyclooxygenase-2 overexpression in human gastric epithelial cells by Helicobacter pylori involves TLR2/TLR9 and c-Src-dependent nuclear factor-kappaB activation

Gastric epithelial cells were incubated with a panel of clinical isolates of Helicobacter pylori, including nonulcer dyspepsia with gastritis (HS, n = 20), gastric ulcer (HU, n = 20), duodenal ulcer (HD, n = 21), and gastric cancer (HC, n = 20). HC strains induced a higher cyclooxygenase-2 (COX-2) expression than those from HS, HD, and HU. The bacterial virulence factors and the host cellular pathways were investigated. Virulence genes of iceA, vacA, babA2, cagA 3' repeat region, and hrgA failed to show any association with the disease status and COX-2 expression. Methylation-specific polymerase chain reaction revealed HC strains not affecting the methylation status of COX-2 promoter. Nuclear factor (NF)-kappaB, NF-interleukin 6, and cAMP response element were found to be involved in COX-2 induction. We explored a novel NF-kappaB activation pathway. The mutants of TLR2 and TLR9, but not TLR4, inhibited H. pylori-induced COX-2 promoter activity, and neutralizing antibodies for TLR2 and TLR9 abolished H. pylori-induced COX-2 expression. Phosphatidylinositol-specific phospholipase C (PI-PLC), protein kinase C (PKC), and Src inhibitors inhibited COX-2 induction. The dominant-negative mutants of NIK and various IkappaB kinase complexes, including IKKbeta (Y188F), IKKbeta (Y199F), and IKKbeta (FF), inhibited the COX-2 promoter activity. Phosphorylation of GST-IKKbeta (132-206) at Tyr188 and Tyr199 by c-Src was found after H. pylori infection. In summary, H. pylori induces COX-2 expression via activations of NF-kappaB, NF-interleukin 6, the cAMP response element. In NF-kappaB activation, H. pylori acts through TLR2/TLR9 to activate both the cascade of PI-PLCgamma/PKCalpha/c-Src/IKKalpha/beta and the cascade of NIK/IKKalpha/beta, resulting in the IkappaBalpha degradation and the expression of COX-2 gene. The COX-2 overexpression may contribute to the carcinogenesis in patients colonized with these strains.     

Role of Helicobacter pylori serology in atrophic body gastritis after eradication treatment

BACKGROUND: It has been reported that 50% of patients with atrophic body gastritis have positive Helicobacter pylori antibody titres only. In atrophic body gastritis, a decrease in H. pylori antibodies after eradication treatment has been reported, suggesting that serology may indicate an active H. pylori infection. AIM: To investigate the time course of H. pylori antibodies and gastric inflammation after eradication treatment in patients with atrophic body gastritis, and to determine whether serology alone can be considered as a valid tool to assess the efficacy of eradication treatment in patients with atrophic body gastritis. METHODS: Twenty-seven patients with atrophic body gastritis (12 serologically H. pylori-positive only, ABG-S+; 15 H. pylori-positive at histology and serology, ABG-H+) were included in the treatment group, and 17 patients (all ABG-S+) in the no treatment group. All patients had gastroscopy plus biopsies evaluated according to the updated Sydney system and H. pylori immunoglobulin G determination: in the treatment group, at baseline and 6 and 24 months after eradication (bismuth-based triple regimens); in the no treatment group, at baseline and after 3 years. RESULTS: In the treatment group, in ABG-S+ patients, H. pylori antibodies decreased significantly 6 months after treatment [37.5 U/mL (16-100 U/mL) vs. 15 U/mL (0--100 U/mL), P < 0.01], but 2 years after treatment no further decrease occurred. In addition, in ABG-H+ patients, a significant decrease in H. pylori antibodies occurred 6 months after treatment [45 U/mL (12.5-100 U/mL) vs. 31 U/mL (0-65 U/mL), P < 0.01], but a further decrease was also observed 2 years after treatment [20 U/mL (0-56 U/mL), P < 0.01]. In ABG-S+ patients, no correlation was observed between the H. pylori antibodies and gastric inflammation score, whereas, in the ABG-H+ group, this correlation was extremely significant (r=0.5991, P < 0.0001). In the no treatment group, at follow-up, a significant decrease in H. pylori antibodies was observed [26 U/mL (15-100 U/mL) vs. 22 U/mL (0-53 U/mL), P < 0.05], but the gastric body inflammation remained unchanged. CONCLUSIONS: This study shows that, in ABG-S+ patients after eradication treatment, serology does not keep in step with gastric inflammation. This suggests that, in patients with atrophic body gastritis, serology alone may not be valid for the assessment of the efficacy of eradication treatment.     

Carditis in patients with gastro-oesophageal reflux disease: results of a controlled study based on both endoscopy and 24-h oesophageal pH monitoring

BACKGROUND: There are conflicting reports on the role of gastro-oesophageal reflux disease (GERD) and Helicobacter pylori infection in the aetiology of carditis. AIM: The role of reflux and H. pylori infection in causing carditis was assessed in 113 consecutive patients with GERD and in 25 controls. METHODS: All subjects underwent endoscopy and pH test and carditis was diagnosed on biopsies taken across the squamocolumnar junction. Helicobacter pylori was assessed by histology and rapid urease test. GERD was diagnosed by endoscopic oesophagitis or abnormal pH test. RESULTS: Carditis was detected in 53 of 71 GERD patients and in 15 of 20 controls. Among patients, 18 showed absent, 39 mild and 14 marked cardia inflammation and their H. pylori infection rates were 17, 23 and 57%, respectively (P < 0.025). Most patients with carditis (68%) lacked H. pylori infection. pH-metry was abnormal in 15 of 18 patients with normal cardia, 33 of 39 with mild carditis and 12 of 14 with marked inflammation. CONCLUSIONS: Carditis is a frequent finding in GERD and controls. Mild, non-active carditis is frequent in GERD patients. Marked inflammation is associated with both H. pylori and abnormal pH testing. Thus, both GERD and H. pylori infection may play a role in inducing carditis.     

Rabeprazole-based eradication therapy for Helicobacter pylori: a large-scale study in Japan

BACKGROUND: Large-scale studies of rabeprazole-based Helicobacter pylori eradication therapy have not been reported in Japan. AIMS: To evaluate H. pylori eradication by rabeprazole-based therapy with reference to antibiotic susceptibility, CYP2C19 genotype, and rabeprazole and clarithromycin dosages. METHODS: From 35 centres 479 H. pylori-positive patients with gastric or duodenal ulcer were randomized to four treatment groups: Group 1 (10 mg rabeprazole + 750 mg amoxicillin + 200 mg clarithromycin twice daily for 7 days); Group 2 (10 mg, 750 mg, 400 mg); Group 3 (20 mg, 750 mg, 200 mg) and Group 4 (20 mg, 750 mg, 400 mg). RESULTS: Eradication rates were 86% (102 of 119), 89% (97 of 109), 91% (106 of 116) and 90% (104 of 115) for Groups 1-4, respectively. The eradication rate was 95% (360 of 379) for clarithromycin-susceptible strains, and 50% (30 of 60) for clarithromycin-resistant strains. The eradication rates were 88% (332 of 379) and 96% (77 of 80) in extensive metabolizers and poor metabolizers, respectively. CONCLUSIONS: Rabeprazole-based therapies achieved 50% eradication of clarithromycin-resistant H. pylori, and even achieved good rates in extensive metabolizers. Accordingly, rabeprazole can be recommended as part of a first-line proton pump inhibitor-based triple therapy for H. pylori.     

Anti-inflammatory and tissue-protectant drug effects: results from a randomized placebo-controlled trial of gastritis patients at high risk for gastric cancer

BACKGROUND: The inflammatory process involving Helicobacter pylori-associated gastritis is thought to lead to epithelial damage and contribute to the development of gastric cancer. Evidence exists from animal and in vitro studies suggesting that tetracyclines have both anti-inflammatory and tissue-protectant effects unrelated to their antimicrobial activity. We attempted to modulate components of H. pylori's inflammatory process by: (i) eliminating the infection; (ii) using tetracycline to alter the host's reaction to the infection without reducing the bacterial load; and (iii) using calcium to counteract the effect of excessive dietary salt. METHODS: We conducted a 16-week placebo-controlled clinical trial with 374 H. pylori-associated gastritis patients randomly assigned to one of five groups: (1) triple therapy consisting of metronidazole, amoxicillin and bismuth subsalicylate for 2 weeks, followed by bismuth alone for 14 weeks; (2) calcium carbonate; (3) triple therapy and calcium carbonate; (4) tetracycline; or (5) placebo. RESULTS: Subjects in the tetracycline and triple therapy groups, but not the calcium carbonate only group, showed a reduction in inflammation and epithelial damage vs. those in the placebo group, independent of a change in H. pylori density and other factors. Our results also indicate that epithelial damage may be affected by mechanisms independent of H. pylori density or inflammation. CONCLUSION: The results are consistent with the hypothesis that tetracycline can decrease inflammation independent of a reduction in the bacterial load. More research is needed to investigate mechanisms leading to epithelial damage which are independent of H. pylori density and inflammation.     

Polaprezinc attenuates the Helicobacter pylori-induced gastric mucosal leucocyte activation in Mongolian gerbils--a study using intravital videomicroscopy

BACKGROUND: We previously demonstrated that Helicobacter pylori colonization evokes gastric mucosal inflammation and an extensive increase in lipid peroxides and glutathione in Mongolian gerbils. Zinc and its derivative, polaprezinc, have been reported to be potent antioxidants in gastric mucosa. AIM: To examine the effect of polaprezinc on gastric mucosal oxidative inflammation in H. pylori-colonized Mongolian gerbils. METHODS: Sixty-eight male Mongolian gerbils were orally inoculated with H. pylori (ATCC43504, 5 x 10(8) CFUs/gerbil; H. pylori group) and 35 gerbils were inoculated with the culture media (control group). Twenty-two gerbils in the H. pylori and 13 gerbils in the control group were fed with diets containing polaprezinc (0.06%, 100 mg/kg, 10 times the usual clinical dose) (H. pylori + polaprezinc group, polaprezinc group). The remaining gerbils were fed a standard laboratory chow diet. Neutrophil infiltration, assessed histologically and by the activity of myeloperoxidase, the contents of CXC-chemokine (GRO/CINC-1-like protein) and the contents of thiobarbituric acid-reactive substances, was evaluated in each group 12 weeks after the inoculation. Separately, gastric mucosal leucocyte activation and capillary perfusion were also assessed using intravital microscopy 2, 4, 8 and 12 weeks after the inoculation. RESULTS: In all H. pylori-inoculated animals, the bacterial infection persisted throughout the experimental period. Gastric mucosal lesion formation in the H. pylori group was significantly inhibited in the H. pylori + polaprezinc group. Elevated levels of myeloperoxidase activity, GRO/CINC-1 and thiobarbituric acid-reactive substances in the H. pylori group at 12 weeks were attenuated significantly by polaprezinc treatment. Enhanced levels of venular leucocyte activation observed in the H. pylori group were attenuated significantly in the H. pylori + polaprezinc group during both the early phase (2 weeks) and late phase (12 weeks). CONCLUSION: Polaprezinc inhibited H. pylori-associated gastric mucosal oxidative inflammation, including initial micro-vascular leucocyte activation, in Mongolian gerbils.     

Randomized trial of omeprazole and metronidazole with amoxycillin or clarithromycin for Helicobacter pylori eradication, in a region of high primary metronidazole resistance: the HERO study

BACKGROUND: The efficacy of omeprazole-based eradication therapies has been determined mostly in populations with low to moderate prevalence of metronidazole resistant Helicobacter pylori, yet resistance is high in many regions. AIM AND METHODS: The H. pylori eradication and duodenal ulcer healing rates after 1 week of either omeprazole 40 mg mane, amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. (OAM) or omeprazole 20 mg b.d., metronidazole 400 mg b. d. and clarithromycin 250 mg b.d. (OMC) were compared in a randomized trial in Australia and New Zealand. Patients had a further 1 week of omeprazole 20 mg. Outcome was assessed at 6 weeks with stringent criteria (endoscopy, biopsies and 13C-urea breath test). RESULTS: Of 220 subjects randomized, the H. pylori eradication rates (all patients treated/per protocol) were 82%/85% for OMC and 58%/63% for OAM (P= 0.001). Pre-treatment metronidazole resistance was present in 56% and clarithromycin resistance in 6%. The eradication rate for primary metronidazole resistance isolates treated with OMC was 80% (CI: 65-90%) compared with 45% (CI: 29-62%) for OAM, whereas for sensitive organisms, the eradication rates were 94% (CI: 79-99%) and 79% (CI: 62-91%), respectively. Duodenal ulcer healing was 96% for OMC and 87% for OAM. Compliance was excellent and both treatments were well-tolerated. CONCLUSIONS: OMC is a well-tolerated, effective therapy for H. pylori eradication and duodenal ulcer healing in this region despite the high metronidazole resistance rate. OAM is less effective, largely due to the impact of metronidazole resistance.