Single- and multiple-dose pharmacokinetics of pipemidic acid in normal human volunteers

Klinge, Erik; Männistö, Pekka T.; Mäntylä, R; Mattila, J.; Hänninen, U.

doi:10.1128/aac.26.1.69

Cited by 17 publications

(2 citation statements)

References 7 publications

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“…The antibiotics shown in bold are reference antibiotics. Values were obtained from three independent experiments and expressed as mean ± SD (n = 9). a The values are derived from the literature 26–30 b Shown as residual viable cell percentage calculated from cell counting under a fluorescence microscope.…”

Section: Resultsmentioning

confidence: 99%

High-Throughput Drug Screening on Borrelia garinii and Borrelia afzelii Identified Hypocrellin A as an Active Drug Candidate Against Borrelia Species

Xin

Liu

et al. 2023

Infect Microb Dis

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Lyme disease (LD) is a tick-transmitted infection caused by Borrelia burgdorferi sensu lato species, which include B. burgdorferi, Borrelia afzelii and Borrelia garinii. The majority of patients with early LD can be cured by the standard treatment, yet some still suffer from posttreatment LD syndrome. The presence of Borrelia persisters has been proposed as a contributing factor, because they cannot be completely eradicated by the currently used antibiotics for LD. Finding new pharmaceuticals targeting Borrelia persisters is crucial for developing more effective treatments. Here, we first confirmed the existence of persisters in B. garinii and B. afzelii cultures and then conducted a high-throughput screening of a custom drug library against persister-rich stationary-phase B. garinii and B. afzelii cultures. Among 2427 compounds screened, hypocrellin A (HA), anthracycline class of drugs and topical antibiotics along with some other natural compounds were identified to have strong potential for killing persisters of B. garinii and B. afzelii. HA was the most active anti-Borrelia compound, capable of eradicating stationary-phase Borrelia persisters, in particular when combined with doxycycline and/or ceftriaxone. Liposoluble antioxidant vitamin E was found to antagonize the activity of HA, indicating HA's target is the cell membrane where HA triggers the generation of reactive oxygen species in the presence of light. HA was found to have distinct bactericidal activity against Borrelia species but had poor or no activity against gram-positive and gram-negative bacteria. Identification of the abovementioned drug candidates may help develop more effective therapies for LD.

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Section: Resultsmentioning

confidence: 99%

High-Throughput Drug Screening on Borrelia garinii and Borrelia afzelii Identified Hypocrellin A as an Active Drug Candidate Against Borrelia Species

Xin

Liu

et al. 2023

Infect Microb Dis

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“…a. The values are derived from the literature[32][33][34][35][36].241 b. Shown as residual viable cell percentage calculated from cell counting under a fluorescence microscope.…”

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confidence: 99%

High-Throughput Drug Screening on Borrelia Garinii and Borrelia Afzelii Identified Hypocrellin A as an Active Drug Candidate against Borrelia Species

Li¹,

Xin²,

Liu³

et al. 2022

Preprint

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Lyme disease (LD) is a tick-transmitted infection caused by Borrelia burgdorferi sensu lato species which includes B. burgdorferi, B. afzelii, and B. garinii. The majority of patients with early LD can be cured by standard treatment, yet some still suffer from post-treatment Lyme disease syndrome (PTLDS). The presence of Borrelia persisters has been proposed as a contributing factor, which cannnot be completely killed by the currently used antibiotics for Lyme disease. Finding new pharmaceuticals targeting Borrelia persisters is crucial in developing more effective treatment. Here, we first confirmed the existence of persisters in cultures of B. garinii and B. afzelii and then conducted high-throughput screening of a custom drug library against persister-rich stationary-phase cultures of B. garinii and B. afzelii. Among 2427 compounds screened, hypocrellin A (HA), anthracycline class of drugs, and topical antibiotics along with some other natural compounds were identified to have strong potential in killing persisters of B. garinii and B. afzelii. HA was the most active anti-Borrelia compound, capable of eradicating stationary-phase Borrelia persisters, in particular when combined with doxycycline and/or ceftriaxone. Liposoluble antioxidant vitamin E was found to antagonize the activity of HA, indicating HA’s target is the cell membrane where HA-triggered reactive oxygen species (ROS) generation took place in the presence of light. HA was found to have distinct bactericidal activity against Borrelia species but had poor or no activity against Gram-positive and Gram-negative bacteria. Identification of the above-mentioned drug candidates may help to develop more effective therapies for LD.

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P

Elks¹,

Ganellin²

1990

Dictionary of Drugs

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Single- and multiple-dose pharmacokinetics of pipemidic acid in normal human volunteers

Cited by 17 publications

References 7 publications

High-Throughput Drug Screening on Borrelia garinii and Borrelia afzelii Identified Hypocrellin A as an Active Drug Candidate Against Borrelia Species

High-Throughput Drug Screening on Borrelia garinii and Borrelia afzelii Identified Hypocrellin A as an Active Drug Candidate Against Borrelia Species

High-Throughput Drug Screening on Borrelia Garinii and Borrelia Afzelii Identified Hypocrellin A as an Active Drug Candidate against Borrelia Species

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