16 research outputs found

    Antimicrobial Activity of Some Trigonella Species

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    The genus Trigonella includes many medicinal and aromatic plant species used in traditional as well as veterinary medicines for different diseases, alone or in combination with other remedies. The crude methanol extracts of 15 Trigonella species were assayed for antimicrobial activity against four medicinally important multidrug resistant clinical isolates, five plant pathogenic bacteria and five fungi. Three species showed a broad spectrum of antibacterial activity inhibiting all the test bacteria. Acidified ethanolic extract of the most promising species, T. suavissima was purified by column chromatography. Characterization of a partially purified ethyl acetate fraction by LC/ESI/MS showed the presence of 7’4’ dihydroxy flavone and (2E)-3-{5-[4-(Ethoxycarbonyl)phenyl]furan-2-yl}prop-2-enoate) Three species showed strong antifungal activity against Aspergillus niger and Fusarium solani. The saponin extract of T. spicata showed a selective activity against A. niger and the sapogenin extract against F. solani. A polyhydroxylated alkaloid was isolated from the sapogenin extract of T. spicata using chromatographic techniques with structural characterization done by LC/ESI/MS, 13C and 1H NMR. The study reveals that Trigonella species are potential sources of natural compounds that may act as antimicrobial agents. It represents the most extensive survey of antimicrobial activity in Trigonella done to date

    Gut Microbial Trimethylamine Is Elevated in Alcohol-Associated Hepatitis and Contributes to Ethanol-Induced Liver Injury in Mice

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    There is mounting evidence that microbes residing in the human intestine contribute to diverse alcohol-associated liver diseases (ALD) including the most deadly form known as alcohol-associated hepatitis (AH). However, mechanisms by which gut microbes synergize with excessive alcohol intake to promote liver injury are poorly understood. Furthermore, whether drugs that selectively target gut microbial metabolism can improve ALD has never been tested. We used liquid chromatography tandem mass spectrometry to quantify the levels of microbe and host choline co-metabolites in healthy controls and AH patients, finding elevated levels of the microbial metabolite trimethylamine (TMA) in AH. In subsequent studies, we treated mice with non-lethal bacterial choline TMA lyase (CutC/D) inhibitors to blunt gut microbe-dependent production of TMA in the context of chronic ethanol administration. Indices of liver injury were quantified by complementary RNA sequencing, biochemical, and histological approaches. In addition, we examined the impact of ethanol consumption and TMA lyase inhibition on gut microbiome structure via 16S rRNA sequencing. We show the gut microbial choline metabolite TMA is elevated in AH patients and correlates with reduced hepatic expression of the TMA oxygenase flavin-containing monooxygenase 3 (FMO3). Provocatively, we find that small molecule inhibition of gut microbial CutC/D activity protects mice from ethanol-induced liver injury. CutC/D inhibitor-driven improvement in ethanol-induced liver injury is associated with distinct reorganization of the gut microbiome and host liver transcriptome. The microbial metabolite TMA is elevated in patients with AH, and inhibition of TMA production from gut microbes can protect mice from ethanol-induced liver injury

    Gut microbe-targeted choline trimethylamine lyase inhibition improves obesity via rewiring of host circadian rhythms.

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    Obesity has repeatedly been linked to reorganization of the gut microbiome, yet to this point obesity therapeutics have been targeted exclusively toward the human host. Here, we show that gut microbe-targeted inhibition of the trimethylamine N-oxide (TMAO) pathway protects mice against the metabolic disturbances associated with diet-induced obesity (DIO) or leptin deficiency (Lepob/ob). Small molecule inhibition of the gut microbial enzyme choline TMA-lyase (CutC) does not reduce food intake but is instead associated with alterations in the gut microbiome, improvement in glucose tolerance, and enhanced energy expenditure. We also show that gut microbial CutC inhibition is associated with reorganization of host circadian control of both phosphatidylcholine and energy metabolism. This study underscores the relationship between microbe and host metabolism and provides evidence that gut microbe-derived trimethylamine (TMA) is a key regulator of the host circadian clock. This work also demonstrates that gut microbe-targeted enzyme inhibitors have potential as anti-obesity therapeutics

    Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

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    BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

    Wirksamkeiten der Individualpädagogik im Ausland nach §35 SGBVIII insbesondere im Hinblick auf die Rückführung ins Heimatland

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    Diese Arbeit kann in der Bereichsbibliothek Hüfferstiftung (Sozialwesen) eingesehen werden

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    Not AvailableThe genus Trigonella includes many medicinal and aromatic plant species used in traditional as well as veterinary medicines for different diseases, alone or in combination with other remedies. The crude methanol extracts of 15 Trigonella species were assayed for antimicrobial activity against four medicinally important multidrug resistant clinical isolates, five plant pathogenic bacteria and five fungi. Three species showed a broad spectrum of antibacterial activity inhibiting all the test bacteria. Acidified ethanolic extract of the most promising species, T. suavissima was purified by column chromatography. Characterization of a partially purified ethyl acetate fraction by LC/ESI/MS showed the presence of 7’4’ dihydroxy flavone and ( 2E ) - 3 - ( 5 - [ 4 - ( Ethoxycarbonyl ) phenyl ] furan - 2 - yl ) prop - 2 - enoate Three species showed strong antifungal activity against Aspergillus niger and Fusarium solani. The saponin extract of T. spicata showed a selective activity against A. niger and the sapogenin extract against F. solani. A polyhydroxylated alkaloid was isolated from the sapogenin extract of T. spicata using chromatographic techniques with structural characterization done by LC/ESI/MS, 13C and 1H NMR. The study reveals that Trigonella species are potential sources of natural compounds that may act as antimicrobial agents. It represents the most extensive survey of antimicrobial activity in Trigonella done to date.Not Availabl
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