Colloid bismuth versus famotidine in the treatment and prevention of duodenal ulcer relapse: results of a double-blind, double dummy randomized study

Summary— Fifty-three consecutive patients with active duodenal ulcer (DU) were randomly included in a double-blind, double-dummy study to test the healing and relapsing rate of two treatment regimens: famotidine 40 mg nocte for 4–8 weeks, followed by 20 mg for 12 months after healing of the ulcer and colloidal bismuth (CBS) (240 mg bid) for 4–8 weeks, followed by placebo maintenance treatment. The results of the short term period confirmed the efficacy of CBS in healing DU (24/25 in CBS group and 19/23 in famotidine group). However, the relapse rate in the CBS-treated group was higher (77.8% at 12 months) than in the famotidine group (35.7%) ( p = 0.041). Only 7 patients (41.2%) were cleared from Helicobacter pylori (HP) after CBS treatment. In conclusion, the high relapse rate observed in CBS treated patients may be related to the high percentage of patients with HP infection in the tested group and support the hypothesis that lack of efficacy of CBS in preventing DU recurrence is related to its poor eradication of HP.     

高效液相色谱法测定复方铝酸铋颗粒中甘草酸含量

目的建立复方铝酸铋颗粒中甘草酸含量的测定方法，完善和提高制剂的质量标准。方法采用高效液相色谱法（HPLC法），以十八烷基硅烷键合硅胶为填充剂，以甲醇-0．2mol／L醋酸铵-冰醋酸（67：33：1）为流动相，检测波长为250nm。结果平均回收率为100．3％，RSD为1．05％（n=6）。结论HPLC法简便、快捷、准确，可用于复方铝酸铋颗粒的质量控制。     

根除幽门螺旋杆菌四联疗法中奥美拉唑对比格犬铋吸收的影响

目的探讨根除幽门螺旋杆菌四联疗法中奥美拉唑对比格犬体内铋吸收的影响。方法 采用双周期随机交叉试验设计,6只健康比格犬随机分为2组,分别先后po给予胶体果胶铋(B)70 mg+甲硝唑(M)250 mg+四环素(T)250 mg〔BMT〕或奥美拉唑(Ome)40 mg+BMT(70+250+250)mg(Ome+BMT),并于给药前和给药后0.5,1,2,3,4,6,8,10,12和14 h采集血样并预处理,建立火焰原子吸收光谱法并测定比格犬血浆中铋的浓度,并计算其主要药动学参数。结果 成功建立了测定铋血药浓度的火焰原子吸收光谱法,比格犬口服BMT和Ome+BMT后铋的cmax分别为21.7±5.3和(37.5±5.4)μg.L-1,AUC0-t分别为116.3±27.4和(170.1±30.4)μg.h.L-1,tmax分别为3.0±0.6和(3.0±0.6)h,(Ome+BMT)组比BMT组的cmax,AUC0-t显著升高(P<0.05)。结论 根除幽门螺旋杆菌四联疗法中奥美拉唑能显著增加比格犬体内铋的吸收。     

Understanding treatment guidelines with bismuth and non-bismuth quadruple Helicobacter pylori eradication therapies

Introduction: Recent Helicobacter pylori treatment guidelines recommend the 4-drug combinations bismuth quadruple therapy and concomitant therapy.

Areas covered: We review antimicrobial therapy for H. pylori in the context of antimicrobial therapy in general and specifically in relation to good antimicrobial stewardship (defined as optimal selection, dose, and duration of an antimicrobial that results in the best clinical outcome for the treatment of infection, with minimal toxicity to the patient and minimal impact on subsequent resistance).

Expert commentary: The lack of regional and local H. pylori susceptibility data prevents implementation of susceptibility-based antimicrobial therapy and forces compromises. Bismuth quadruple therapy employing at least 1,500 mg of metronidazole for 14 days is effective despite metronidazole resistance. The main drawback is side effects causing reduced adherence. Versions where amoxicillin replaces metronidazole or tetracycline also appear effective. It is likely that bismuth quadruple therapy can be simplified by giving bismuth and possibly tetracycline b.i.d., possibly with fewer side effects. Concomitant therapy (a proton pump inhibitor, metronidazole, clarithromycin, amoxicillin) is ineffective with dual clarithromycin-metronidazole resistance and all patients receive at least one unnecessary antibiotic thus promoting antimicrobial resistance worldwide. Concomitant therapy should be abandoned when susceptibility testing becomes widespread or an alternate becomes available.     

醋氨己酸锌治疗幽门螺杆菌阳性的十二指肠溃疡

目的 :观察醋氨己酸锌 (ZAC)治疗幽门螺杆菌 (Hp)阳性的十二指肠溃疡 (DU )的疗效。方法 :胃镜证实的 6 2例Hp阳性DU ,随机分为 2组 :ZAC组 32例 (男性 18例 ,女性 14例 ;年龄 31a±s8a) ,应用ZAC 0 .3g ,po ,tid ;胶态次枸橼酸铋(CBS)组 30例 (男性 16例 ,女性 14例 ;年龄 30a± 9a) ,应用CBS 0 .2 4g ,po ,bid ;2组均同时应用雷尼替丁 0 .15g ,po ,bid。疗程均 4wk。结果 :溃疡愈合率ZAC组为 4 3% ,CBS组为 4 2 % (P >0 .0 5)。临床疼痛症状缓解情况近似。Hp根除率ZAC组77% ,CBS组为 75% (P >0 .0 5)。不良反应发生率ZAC组 13% ,CBS组 4 6 % (P <0 .0 5)。结论 :ZAC和CBS对Hp阳性的DU有相似的作用。     

Pharmacokinetic Interactions between Tegoprazan and Metronidazole/Tetracycline/Bismuth and Safety Assessment in Healthy Korean Male Subjects

PurposeTegoprazan is a potassium-competitive acid blocker used for gastric acid suppression, which may be used with Helicobacter pylori eradication therapies. The goal of this study was to evaluate the pharmacokinetic interaction between tegoprazan and triple-antibiotic therapy containing metronidazole, tetracycline, and bismuth.Methods: An open-label, 2-cohort, randomized, multiple-dose, crossover study was conducted in healthy subjects. In cohort 1, tegoprazan (100 mg/d) was administered orally with or without triple-antibiotic therapy (1500 mg/d metronidazole, 2000 mg/d tetracycline, and 1200 mg/d bismuth) for 7 days in each period. In cohort 2, triple-antibiotic therapy was administered orally with or without tegoprazan for 7 days in each period. Pharmacokinetic blood samples were collected within 24 h after the last dose. Safety assessments were performed.Findings: Eleven cohort 1 subjects and ten cohort 2 subjects were included in the pharmacokinetic analysis. The AUC_τ and C_max at steady state geometric mean ratios (90% CIs) were 0.78 (0.73–0.83) and 0.75 (0.68–0.82) for tegoprazan; 0.77 (0.68–0.88) and 0.84 (0.72–0.98) for tegoprazan metabolite M1; 1.03 (0.98–1.08) and 1.08 (0.99–1.18) for metronidazole; 0.63 (0.56–0.70) and 0.64 (0.56–0.74) for tetracycline; and 1.55 (0.99–2.44) and 1.38 (0.72–2.66) for bismuth, respectively. All reported adverse events were mild.ImplicationsChanges in the tegoprazan, tetracycline, and bismuth pharmacokinetic parameters were detected after concurrent administration. These changes were considered mainly due to the pharmacodynamic effect of tegoprazan. The adverse events were predictable and reported as frequent adverse events during triple-antibiotic therapy. There were no significant differences in safety or tolerability between quadruple therapy, including tegoprazan and triple-antibiotic therapy. ClinicalTrials.gov identifier: NCT04066257.     

幽门螺杆菌不同治疗方案的疗效评估

目的 对本院门诊患者根除幽门螺杆菌(Hp)的不同治疗方案进行疗效比较.方法 选择2005年1月～2007年7月我院就诊的幽门螺杆菌治疗前后资料完整的患者522例,质子泵抑制剂(PPI) 克拉霉素 硝基咪唑类121例,PPI 克拉霉素 阿莫西林135例,PPI 硝基咪唑类 阿莫西林80例;枸橼酸铋雷尼替丁 克拉霉素 硝基咪唑类63例,枸橼酸铋雷尼替丁(RBC) 克拉霉素 阿莫西林81例,RBC 硝基咪唑类 阿莫西林42例.结果 PPI 两种抗生素的治疗方案中,PPI 克拉霉素 阿莫西林的Hp根除率显著高于PPI 克拉霉素 硝基咪唑组,而与PPI 阿莫西林 硝基咪唑组比较无显著性差异;RBC 两种抗生素的治疗方案中,RBC 克拉霉素 阿莫西林的Hp根除率最高;在使用相同的抗生素的情况下,PPI组与RBC组根除Hp比较无显著性差异.结论 选择PPPI/RBC 克拉霉素 阿莫西林能更有效地根除Hp.     

Hydrothermal Crystallization of Bismuth Oxychlorides (BiOCl) Using Different Shape Control Reagents

Bismuth oxychloride photocatalysts were obtained using solvothermal synthesis and different additives (CTAB—cetyltrimethylammonium bromide, CTAC—cetyltrimethylammonium chloride, PVP–polyvinylpyrrolidone, SDS–sodium dodecylsulphate, U—urea and TU—thiourea). The effect of the previously mentioned compounds was analyzed applying structural (primary crystallite size, crystal phase composition, etc.), morphological (particle geometry), optical (band gap energy) parameters, surface related properties (surface atoms’ oxidation states), and the resulted photocatalytic activity. A strong dependency was found between the surface tension of the synthesis solutions and the overall morpho-structural parameters. The main finding was that the characteristics of the semiconductors can be tuned by modifying the surface tension of the synthesis mixture. It was observed after the photocatalytic degradation, that the white semiconductor turned to grey. Furthermore, we attempted to explain the gray color of BiOCl catalysts after the photocatalytic decompositions by Raman and XPS studies.     

Atomic-scale insights into quantum-order parameters in bismuth-doped iron garnet

Bismuth and rare earth elements have been identified as effective substituent elements in the iron garnet structure, allowing an enhancement in magneto-optical response by several orders of magnitude in the visible and near-infrared region. Various mechanisms have been proposed to account for such enhancement, but testing of these ideas is hampered by a lack of suitable experimental data, where information is required not only regarding the lattice sites where substituent atoms are located but also how these atoms affect various order parameters. Here, we show for a Bi-substituted lutetium iron garnet how a suite of advanced electron microscopy techniques, combined with theoretical calculations, can be used to determine the interactions between a range of quantum-order parameters, including lattice, charge, spin, orbital, and crystal field splitting energy. In particular, we determine how the Bi distribution results in lattice distortions that are coupled with changes in electronic structure at certain lattice sites. These results reveal that these lattice distortions result in a decrease in the crystal-field splitting energies at Fe sites and in a lifted orbital degeneracy at octahedral sites, while the antiferromagnetic spin order remains preserved, thereby contributing to enhanced magneto-optical response in bismuth-substituted iron garnet. The combination of subangstrom imaging techniques and atomic-scale spectroscopy opens up possibilities for revealing insights into hidden coupling effects between multiple quantum-order parameters, thereby further guiding research and development for a wide range of complex functional materials.

The element bismuth has been chosen as a substituent, or major element, in a diverse range of functional materials, including multiferroics, superconductors, and catalysts (1–3). On account of the often significantly improved performance and various unique phenomena when bismuth is introduced in functional materials, investigations on the local order parameters underpinning such effects have attracted considerable attention. In the past few years, it has been verified that bismuth doping is also an effective method to enhance the performance of magneto-optical devices (4, 5). Among the iron oxides, ferrimagnetic insulators with the complex iron garnet structure R₃Fe₅O₁₂ (where R is an element with large radius) are already widely utilized in magneto-optic devices owing to their combination of small spin-wave damping, good optical transparency, and a pronounced Faraday effect (6–12). The strength of the Faraday effect, which describes a rotation of the plane of polarization of electromagnetic radiation in a magnetic field, is linearly proportional to the Verdet constant (13, 14) for a given material, which for magneto-optical materials such as substituted garnets depends strongly on the coupling effect of multiple quantum-order parameters (15, 16), including those of lattice, spin, and electronic orbitals (12, 17, 18). In particular, diverse polyhedral sites in the garnet structure are bridged via oxygen atoms with a strong exchange interaction effect, resulting in complex electronic and crystal structures (19–22). Although pure yttrium iron garnet (YIG) has several advantages in terms of magneto-optical response, it has not been widely applied in integrated devices due to its low Verdet constant, resulting in a limited Faraday rotation (23, 24). Due, however, to its chemical flexibility, selective substitution has been established as an effective method to tune various physical properties of iron garnets (7, 12, 25, 26), and it is noteworthy that Bi-substituted lutetium iron garnet films prepared via liquid phase epitaxy (LPE) demonstrate an appreciable enhancement in magneto-optical performance (8). Several models based on diamagnetic transitions have been proposed to explain the effect of Bi substitution on magneto-optical response (4, 12, 17, 19, 21, 27–30), in each case with a strong dependence on the crystal energy levels of the Fe³⁺ ions in differently coordinated lattice sites. There is still, however, a lack of experimental evidence to test these models, as this requires the distribution of substituent atoms to be characterized and related to their effect on the crystal lattice and electronic structure at different lattice sites. In this work, we address this limitation by the use of several advanced electron microscopy techniques (31–40) applied synergistically to a Bi-substituted lutetium iron garnet.     

呋喃唑酮与胶体铋剂联合应用治疗幽门螺杆菌相关性胃炎的疗效观察

应用胶体铋剂（ＣＢＳ）与不同剂量的呋喃唑酮（Ｆ）联合治疗Ｈｐ阳性慢性胃炎患者。１７３例病人随机分为５组（ＣＢ８组、Ｆ０．２组、ＣＢＳ＋Ｆ０．２组、ＣＢＳ＋Ｆ０．１组、ＣＢＳ＋Ｆ０．０５组）服药４周（ＣＢＳ４周＋Ｆ２周），Ｈｐ根除率分别为２３．３％、５９．３％、１００％、９１．３％和６１．９％；活动性胃炎消退率分别为１４．０％、４８．１％、７０．９％、８６．７％和５３．３％；副作用发生率分别为４．６％、２１．８％、２３．５％、７．１％和１４．８％。ＣＢＳ＋Ｆ０．２及ＣＢＳ＋Ｆ０．１组Ｈｐ根除率及活动性胃炎消退率均显著高于其它三组（Ｐ＜００５）；且ＣＢＳ＋Ｆ０．１与ＣＢＳ＋Ｆ０．２疗效相当，Ｈｐ根除率可达９０％以上，副作用程度明显减轻，是较理想的根除Ｈｐ方案。