克拉霉素漂浮-生物粘附微囊的制备及性能研究

选用乳化-溶剂挥发法制备乙基纤维素载药微球(EMs), 并通过内部凝胶化法进行包衣制得海藻酸钠-乙基纤维素载药微囊(AEMs), 最后通过离子交联法进一步包衣制得壳聚糖-海藻酸钠-乙基纤维素载药微囊(CAEMs). 研究克拉霉素漂浮\|生物粘附微囊的制备工艺, 并考察微囊的体外漂浮性能、 粘附性能及体内滞留性能. 结果表明, CAEMs球形度较好, 药物包封率为72.3%~78.2%, 载药量为7.1%~12.7%. 在pH=5的醋酸缓冲液中, 6 h时的累积释放率为56.6%~70.6%, 漂浮率大于70%, 4 h时的体内滞留率为60.5%. CAEMs有望通过延长药物胃内滞留时间, 在临床用于根除幽门螺旋杆菌, 从而降低消化道溃疡的复发率.     

Synthesis and Characterisation of Bismuth(III) Aminoarenesulfonate Complexes and Their Powerful Bactericidal Activity against Helicobacter pylori

The synthesis and characterisation of nine new tris‐substituted bismuth(III) aminoarenesulfonates of the general formula [Bi(O₃S‐R^N)₃] (R^N=o‐aminophenyl 1 , m‐aminophenyl 2 , 6‐amino‐3‐methoxyphenyl 3 , p‐aminophenyl 4 , 2‐pyridyl 5 , o‐aminonaphthyl 6 , 5‐aminonaphthyl 7 , 4‐amino‐3‐hydroxynaphthyl 8 and 5‐isoquinolinyl 9 ) is described. Two synthetic strategies, using Ag₂O and [Bi(OtBu)₃], were explored and compared. The possibility to access heteroleptic bismuth(III) complexes with the new silver(I) metathesis reaction is demonstrated with the synthesis of the heteroleptic bismuth(III) aminoarenesulfonate complexes [PhBi(O₃S‐P2)₂(dmso)] 10 , [Ph₂Bi(O₃S‐P2)]_∞ 11 and [PhBi(O₃S‐P2)₂]_∞ 12 , of which the solid state structures 10 and 12 are presented (2P‐SO₃^?=2‐pyridinesulfonate). These complexes offer remarkable in‐vitro activity against three standard laboratory strains of Helicobacter pylori (H. pylori) as demonstrated by their exceptionally low minimum inhibitory concentration (MIC) values of 0.049 μg mL^?1 for the strains 251 and B128, which places most MIC values in the nano‐molar region. These results demonstrate the importance of the amino functionality in addition to the sulfonate group on the bactericidal properties against H. pylori.     

Monitoring the Reaction of the Body State to Antibiotic Treatment against Helicobacter pylori via Infrared Spectroscopy: A Case Study

The current understanding of deviations of human microbiota caused by antibiotic treatment is poor. In an attempt to improve it, a proof-of-principle spectroscopic study of the breath of one volunteer affected by a course of antibiotics for Helicobacter pylori eradication was performed. Fourier transform spectroscopy enabled searching for the absorption spectral structures sensitive to the treatment in the entire mid-infrared region. Two spectral ranges were found where the corresponding structures strongly correlated with the beginning and end of the treatment. The structures were identified as methyl ester of butyric acid and ethyl ester of pyruvic acid. Both acids generated by bacteria in the gut are involved in fundamental processes of human metabolism. Being confirmed by other studies, measurement of the methyl butyrate deviation could be a promising way for monitoring acute gastritis and anti-Helicobacter pylori antibiotic treatment.     

Anti-Helicobacter pylori Activity of Artemisia ludoviciana subsp. mexicana and Two of Its Bioactive Components,Estafiatin and Eupatilin

Artemisia ludoviciana subsp. mexicana has been traditionally used for the treatment of digestive ailments such as gastritis, whose main etiological agent is Helicobacter pylori. In a previous screening study, the aqueous extract exhibited a good in vitro anti-H. pylori activity. With the aim of determining the efficacy of this species as a treatment for H. pylori related diseases and finding bioactive compounds, its aqueous extract was subjected to solvent partitioning and the fractions obtained were tested for their in vitro anti-H. pylori effect, as well as for their in vivo gastroprotective and anti-inflammatory activities. The aqueous extract showed a MIC = 250 µg/mL. No acute toxicity was induced in mice. A gastroprotection of 69.8 ± 3.8%, as well as anti-inflammatory effects of 47.6 ± 12.4% and 38.8 ± 10.2% (by oral and topical administration, respectively), were attained. Estafiatin and eupatilin were isolated and exhibited anti-H. pylori activity with MBCs of 15.6 and 31.2 µg/mL, respectively. The finding that A. ludoviciana aqueous extract has significant anti-H. pylori, gastroprotective and anti-inflammatory activities is a relevant contribution to the ethnopharmacological knowledge of this species. This work is the first report about the in vivo gastroprotective activity of A. ludoviciana and the anti-H. pylori activity of eupatilin and estafiatin.     

Synthesis and Evaluation of Thymol-Based Synthetic Derivatives as Dual-Action Inhibitors against Different Strains of H. pylori and AGS Cell Line

Following a similar approach on carvacrol-based derivatives, we investigated the synthesis and the microbiological screening against eight strains of H. pylori, and the cytotoxic activity against human gastric adenocarcinoma (AGS) cells of a new series of ether compounds based on the structure of thymol. Structural analysis comprehended elemental analysis and ¹H/¹³C/¹⁹F NMR spectra. The analysis of structure–activity relationships within this molecular library of 38 structurally-related compounds reported that some chemical modifications of the OH group of thymol led to broad-spectrum growth inhibition on all isolates. Preferred substitutions were benzyl groups compared to alkyl chains, and the specific presence of functional groups at para position of the benzyl moiety such as 4-CN and 4-Ph endowed the most anti-H. pylori activity toward all the strains with minimum inhibitory concentration (MIC) values up to 4 µg/mL. Poly-substitution on the benzyl ring was not essential. Moreover, several compounds characterized by the lowest minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) values against H. pylori were also tested in order to verify a cytotoxic effect against AGS cells with respect to 5-fluorouracil and carvacrol. Three derivatives can be considered as new lead compounds alternative to current therapy to manage H. pylori infection, preventing the occurrence of severe gastric diseases. The present work confirms the possibility to use natural compounds as templates for the medicinal semi-synthesis.     

Vegetable Extracts and Nutrients Useful in the Recovery from Helicobacter pylori Infection: A Systematic Review on Clinical Trials

Helicobacter pylori (H. pylori) infections affect almost half of the world’s population, with gradually increasing incidence in developed countries. Eradication of H. pylori may provide significant benefits to the affected individual by healing a number of gastrointestinal and extra-digestive disorders. But due to increased microbial resistance and lack of patient adherence to the therapy, the eradication rate of H. pylori is below 80% with current pharmacological therapies. The usage of botanicals for their therapeutic purposes and medicinal properties have been increased in last decades. They can be use as alternative H. pylori treatments, especially against drug-resistant strains. Epidemiological studies have revealed that people with lower vegetable and micronutrient intake may be at increased risk of H. pylori infection. We have undertaken a review of clinical trials to evaluate the efficacy of vegetable extracts and micronutrients in patients with H. pylori. Various databases, such as Google Scholar, PubMed, Scopus, Web of Science, and the Cochrane Library, were searched for the articles published in English. A total of 24 clinical studies (15 for vegetable extracts and 9 for micronutrients) were selected to be reviewed and summarized in this article. Vegetable extracts (Broccoli sprouts, curcumin, Burdock complex, and Nigella sativa) and micronutrients (vitamin C and E) were not found to be as effective as single agents in H. pylori eradication, rather their efficacy synergized with conventional pharmacological therapies. Conversely, GutGard was found to be significantly effective as a single agent when compared to placebo control.     

幽门螺杆菌感染引起非消化系统疾病的研究进展

幽门螺杆菌是一种革兰氏阴性微需氧型细菌, 可引起消化性溃疡、膜相关淋巴组织淋巴瘤和萎缩性胃炎, 是胃癌的主要诱因. 但近年来, 流行病学调查和动物实验数据提示, 该菌感染与一些非消化系统疾病, 如缺铁性贫血、特发性血小板减少性紫癜、菌血症、肺炎以及类风湿性关节炎等的发生密切相关. 本文就幽门螺杆菌感染引发非消化系统疾病的新进展进行系统剖析, 以期全面展现幽门螺杆菌感染的新领域.     

β-Carotene Inhibits Expression of Matrix Metalloproteinase-10 and Invasion in Helicobacter pylori-Infected Gastric Epithelial Cells

Matrix metalloproteinases (MMPs), key molecules of cancer invasion and metastasis, degrade the extracellular matrix and cell–cell adhesion molecules. MMP-10 plays a crucial role in Helicobacter pylori-induced cell-invasion. The mitogen-activated protein kinase (MAPK) signaling pathway, which activates activator protein-1 (AP-1), is known to mediate MMP expression. Infection with H. pylori, a Gram-negative bacterium, is associated with gastric cancer development. A toxic factor induced by H. pylori infection is reactive oxygen species (ROS), which activate MAPK signaling in gastric epithelial cells. Peroxisome proliferator-activated receptor γ (PPAR-γ) mediates the expression of antioxidant enzymes including catalase. β-Carotene, a red-orange pigment, exerts antioxidant and anti-inflammatory properties. We aimed to investigate whether β-carotene inhibits H. pylori-induced MMP expression and cell invasion in gastric epithelial AGS (gastric adenocarcinoma) cells. We found that H. pylori induced MMP-10 expression and increased cell invasion via the activation of MAPKs and AP-1 in gastric epithelial cells. Specific inhibitors of MAPKs suppressed H. pylori-induced MMP-10 expression, suggesting that H. pylori induces MMP-10 expression through MAPKs. β-Carotene inhibited the H. pylori-induced activation of MAPKs and AP-1, expression of MMP-10, and cell invasion. Additionally, it promoted the expression of PPAR-γ and catalase, which reduced ROS levels in H. pylori-infected cells. In conclusion, β-carotene exerts an inhibitory effect on MAPK-mediated MMP-10 expression and cell invasion by increasing PPAR-γ-mediated catalase expression and reducing ROS levels in H. pylori-infected gastric epithelial cells.     

Online immunoaffinity assay-CE using magnetic nanobeads for the determination of anti-Helicobacter pylori IgG in human serum

About two-thirds of the world's population is infected with Helicobacter pylori (H. pylori). This Gram-negative bacterium is the most important etiological agent of chronic active type B gastritis and peptic ulcer diseases. Conventional methods such as gastric biopsy, ELISA and culture, require a long time for the determination of H. pylori infections. Moreover, the antibodies in human serum sample are capable to react immunologically with the purified H. pylori antigens immobilized on different kinds of support like magnetic nanobeads. In this study, we have developed an online immunoaffinity assay-CE to determine the concentration of anti-H. pylori IgG using magnetic nanobeads as a support of the immunological affinity ligands and an LIF as a detector. The separation was performed in 0.1 M glycine-HCl, pH 2, as the background electrolyte. The linear calibration curve to predict the concentration of H. pylori-specific immunoglobulin G antibodies in serum was produced within the range of 0.12-100 U/mL. The linear regression equation was i = 492.86+96.03 × C(anti-H. pylori), with the linear regression coefficient r(2) = 0.999. The LOD calculated by fluorescence detection procedure was of 0.06 U/mL. The whole assay was done in no more than 35 min and it was entirely automatized. The development of immunoaffinity assay-CE in this study demonstrates that there is a large possibility to introduce nanotechnology in several fields with significant advantages over the classic methodologies. Our proposition comprises the diagnosis and screening field.     

幽门螺杆菌相关性的十二指肠溃疡与发锌关系研究

６８例幽门螺杆菌（ＨＰ）相关性的十二指肠溃疡（ＤＵ）患者的发锌明显低于对照（Ｐ〈０．０１），缺锌与ＨＰ相关性的ＤＵ密切相关，因此发锌作为一种检测方法和在治疗上作为补锌的依据具有一定的临床意义。