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Aim: To compare the effectiveness and safety of vonoprazan-based therapy with proton pump inhibitor (PPI)-based therapies to treat Helicobacter pylori ( H. pylori )., Methods: We retrospectively analysed data from first-line (vonoprazan or PPI with 200 mg clarithromycin and 750 mg amoxicillin twice daily for 7 d) ( n = 1353) and second-line (vonoprazan or PPI with 250 mg metronidazole and 750 mg amoxicillin twice daily for 7 d) ( n = 261) eradication treatments for H. pylori -positive patients with associated gastrointestinal diseases from April 2014 to December 2015 at Hattori Clinic, Japan. The primary endpoint was the eradication rate, which was assessed with a full analysis set. The secondary endpoints were adverse events and related factors., Results: After the first-line treatments, the eradication rates for vonoprazan, esomeprazol, rabeprazole, and lansoprazole were 87.9% (95%CI: 84.9%-90.5%), 71.6% (95%CI: 67.5%-75.5%), 62.9% (95%CI: 52.0%-72.9%), and 57.3% (95%CI: 50.4%-64.1%), respectively. The vonoprazan eradication rate was significantly higher than that of the PPIs ( P < 0.01). Interestingly, smoking did not affect the H. pylori eradication rate in the vonoprazan group ( P = 0.34), whereas it decreased the rates in the PPI groups ( P = 0.013). The incidence of adverse events in the vonoprazan group was not different from the PPI group ( P = 0.054), although the vonoprazan group exhibited a wider range of adverse events. Vonoprazan-based triple therapy was highly effective as a second-line treatment, with an eradication rate similar to that of PPI-based therapy., Conclusion: Vonoprazan might be superior to PPIs in first-line H. pylori therapy, particularly for smokers. However, caution is required due to possible adverse events., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interest related to this manuscript.

New cytotoxic substances, designated BE-52440A and B, were isolated from the mycelium of Streptomyces sp. A52440. The active principles were extracted from the mycelium by methanol and purified by silica gel column chromatography. BE-52440A and B exhibited cytotoxic activity against murine and human tumor cell lines.

BE-22179, a novel cyclic depsipeptide antibiotic having two 3-hydroxyquinoline moieties, inhibited the DNA-relaxing activity of L1210 topoisomerase II completely at 0.08 microM. This effect was far stronger than that of VP-16. However, it did not show any marked effect on topoisomerase II-mediated DNA cleavage. BE-22179 was ineffective in inhibiting the DNA relaxation by topoisomerase I at concentrations up to 10 microM, but showed DNA-intercalating ability (DNA unwinding) at 30 microM. The structure of BE-22179 is quite novel for a topoisomerase II inhibitor. Echinomycin, a quinoxaline antibiotic structurally related to BE-22179, interfered with DNA relaxation by topoisomerase II, though the effect was not due to inhibition of the catalytic activity of topoisomerase II but to conformational change of DNA based on its intercalation into DNA. Therefore, the potent inhibitory activity on topoisomerase II might not be a common activity of quinoxaline antibiotics, but might rather be specific to BE-22179. BE-22179 prevented DNA synthesis as well as RNA synthesis in L1210 cells and inhibited the growth of the cells. However, it remains unclear to what extent the topoisomerase II inhibition was responsible for the cytotoxicity of BE-22179.

A new topoisomerase II inhibitor, designated BE-22179, was isolated from the culture broth of Streptomyces sp. A22179, which resembles "Streptomyces gangtokensis". The inhibitor was extracted from the mycelial cake of the culture broth with organic solvent and successively purified by silica gel chromatography. BE-22179 inhibited topoisomerase II strongly but not topoisomerase I and showed potent antitumor activity against various tumor cell lines both in vitro and in vivo.

New antitumor substances, designated BE-12406A and BE-12406B, were isolated from the culture broth of a streptomycete, strain BA 12406. The active principles were extracted from mycelium by methanol and successively purified by silica gel column chromatography and preparative TLC. BE-12406A and BE-12406B inhibited the growth of vincristine-resistant or doxorubicin-resistant P388 murine leukemia cell lines as well as their parent sensitive cell line. In in vivo experiments, BE-12406A inhibited the growth of S-180 murine ascites tumor.

The structure of BE-12406A and BE-12406B, which were isolated from the culture broth of a streptomycete as antitumor substances, were determined by means of spectral analyses and chemical studies. The structure of BE-12406A is 1-hydroxy-10-methoxy-8-methyl-12-alpha- L-rhamnopyranosyloxy-6H-benzo[d]naphtho[1,2-b]pyran-6-one, and that of BE-12406B is 1,10-dihydroxy-8-methyl-12-alpha-L-rhamnopyranosyloxy-6H- benzo[d]naphtho[1,2-b]pyran-6-one.

Experiments were conducted to assess the effects of miporamicin (MPM) on prenatal and postnatal development of fetuses and offsprings of rats receiving the compound at oral dosages of 40, 200, or 1,000 mg/kg/day during the organogenesis stage of gestation. The drug treatment had no appreciable effect on maternal body weight during pregnancy or lactation period. The rats showed decreased food intake and increased water intake during gestation period in the groups given greater than or equal to 200 mg/kg/day, and increased food and water intakes during lactation period in the group given 1,000 mg/kg/day. There was no macroscopic evidence of changes indicative of any effect of the treatment in the viscera of rat dams at terminal necropsy. Observation of the fetuses did not reveal any effect of the treatment with MPM with respect to the number of implantations, the number of living fetuses, the death rate of fetuses or incidence of external, visceral, or skeletal anomalies. Male fetal weights were low in the groups given greater than or equal to 200 mg/kg/day. Observation of the offspring post partum failed to disclose any abnormalities indicative of adverse effects of the treatment with respect to birth index, viability index, weaning index, postnatal external differentiation, body weight changes, external morphology, skeleton, viscera, organ weight, functional and behavioral tests, emotion, learning ability, or reproductive performance, or in respect of prenatal development of their fetuses (F2). It is concluded from the results that no effect dose levels of MPM was 40 mg/kg/day in rat dams, 40 mg/kg/day also for their fetuses, and 1,000 mg/kg/day for postnatal development of the offspring under the experimental conditions described.