Gastric infection with Helicobacter pylori is a cosmopolitan problem, and is especially common in developing regions where there is also a high prevalence of gastric cancer. These infections are known to cause gastritis and peptic ulcers, and dramatically enhance the risk of gastric cancer. Eradication of this organism is an important medical goal that is complicated by the development of resistance to conventional antimicrobial agents and by the persistence of a low level reservoir of H. pylori within gastric epithelial cells. Moreover, economic and practical problems preclude widespread and intensive use of antibiotics in most developing regions. We have found that sulforaphane [(؊)-1-isothiocyanato-(4R)-(methylsulfinyl)butane], an isothiocyanate abundant as its glucosinolate precursor in certain varieties of broccoli and broccoli sprouts, is a potent bacteriostatic agent against 3 reference strains and 45 clinical isolates of H. pylori [minimal inhibitory concentration (MIC) for 90% of the strains is
Sulforaphane, an isothiocyanate abundant in the form of its glucosinolate precursor in broccoli sprouts, has shown in vitro activity against Helicobacter pylori. We evaluated the effect of sulforaphane in vivo against this bacterium by using human gastric xenografts in nude mice. H. pylori was completely eradicated in 8 of the 11 sulforaphane-treated grafts. This result suggests that sulforaphane might be beneficial in the treatment of H. pylori-infected individuals.The recommended treatment of Helicobacter pylori-associated diseases today includes a combination of two or more antibiotics with an inhibitor of acid secretion. However, even with these treatments, some bacteria may persist, in a nongrowing, tolerant form or possibly intracellularly (5,7,10). This may lead to eradication failure, which is defined as the persistence of H. pylori at least 1 month after the end of antimicrobial therapy (9). Moreover, development of resistance of H. pylori strains to one or more of the antibiotics commonly used has been demonstrated previously (28). Thus, a need for new therapeutic agents that are effective against extracellular and potentially intracellular forms of H. pylori exists. We recently showed that sulforaphane, an isothiocyanate abundant in the form of its glucosinolate precursor in broccoli and broccoli sprouts, is a potent bactericidal agent against both extra-and intracellular H. pylori in vitro (11). Substantial quantities of isothiocyanates (up to 100 mg daily) and even greater quantities of their glucosinolate precursors are widely consumed by humans (12,13,29). They may act locally within the gastrointestinal tract or may distribute systemically after conversion to their cognate isothiocyanates (12,15,34). In this study, we investigated the efficacy of sulforaphane in vivo against H. pylori by using a recently developed model which uses human gastric xenografts in nude mice (22).Sulforaphane, i.e., [(Ϫ)-1-isothiocyanato-(4R)-(methylsulfinyl)butane] was kindly provided by J. W. Fahey (Johns Hopkins University School of Medicine, Baltimore, Md.). Stock solutions were prepared in acetonitrile, and further dilutions were made in sterile water. H. pylori strain 26695, which was previously adapted for use in the gastric xenograft model (23), was used for graft inoculation. The strain was grown on Columbia agar supplemented with 10% horse blood under microaerobic conditions as previously described (22). For this isolate, the MIC of sulforaphane was 4 g/ml, as determined by using the agar dilution method (pH 7.4) as recommended by the National Committee for Clinical Laboratory Standard (NCCLS) (30).Xenografts exhibiting human mature gastric epithelium and acidic secretion were obtained in nude mice as previously described (22) and with the approval of the French National Consultative Ethical Committee. Bacterial inoculation was performed by using a catheter that was implanted in the xenograft lumen (22). Two weeks after inoculation, each graft was microsurgically opened. Mucus was sampled for qualitative cult...
The antibacterial activity of sulforaphane [4-(methylsulfinyl)butyl isothiocyanate] has been previously described. We have analysed the activities of 12 isothiocyanates (ITC) including sulphoraphane on 25 strains of Helicobacter pylori using an agar dilution assay. In addition, bactericidal effects against H. pylori were determined for the 6 most active ITCs, both directly and against intracellular bacteria in cultured human epithelial (HEp-2) cells. The MIC90 values for these ITCs ranged between 4 and 32 microg/mL and four of the most potent compounds exhibited bactericidal activity against both extra- and intracellular bacteria. Overall, our data indicate that ITCs have a potent antibacterial effect against H. pylori and these naturally occurring phytochemicals might have potential as novel therapeutic agents for H. pylori eradication.
Bacteremia caused by Francisella tularensis is rare and has been reported mainly in the United States and infrequently in Europe. We report herein the first case of bacteremic F. tularensis pneumonia in an immunocompetent individual in southern Europe
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