The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Steven W Lindsay - One of the best experts on this subject based on the ideXlab platform.

  • can topical Insect Repellents reduce malaria a cluster randomised controlled trial of the Insect Repellent n n diethyl m toluamide deet in lao pdr
    PLOS ONE, 2013
    Co-Authors: Vanessa Chenhussey, Ilona Carneiro, Hongkham Keomanila, Robert Gray, Sihamano Bannavong, Saysana Phanalasy, Steven W Lindsay
    Abstract:

    Background Mosquito vectors of malaria in Southeast Asia readily feed outdoors making malaria control through indoor Insecticides such as long-lasting Insecticidal nets (LLINs) and indoor residual spraying more difficult. Topical Insect Repellents may be able to protect users from outdoor biting, thereby providing additional protection above the current best practice of LLINs. Methods and Findings A double blind, household randomised, placebo-controlled trial of Insect Repellent to reduce malaria was carried out in southern Lao PDR to determine whether the use of Repellent and long-lasting Insecticidal nets (LLINs) could reduce malaria more than LLINs alone. A total of 1,597 households, including 7,979 participants, were recruited in June 2009 and April 2010. Equal group allocation, stratified by village, was used to randomise 795 households to a 15% DEET lotion and the remainder were given a placebo lotion. Participants, field staff and data analysts were blinded to the group assignment until data analysis had been completed. All households received new LLINs. Participants were asked to apply their lotion to exposed skin every evening and sleep under the LLINs each night. Plasmodium falciparum and P. vivax cases were actively identified by monthly rapid diagnostic tests. Intention to treat analysis found no effect from the use of Repellent on malaria incidence (hazard ratio: 1.00, 95% CI: 0.99–1.01, p = 0.868). A higher socio-economic score was found to significantly decrease malaria risk (hazard ratio: 0.72, 95% CI: 0.58–0.90, p = 0.004). Women were also found to have a reduced risk of infection (hazard ratio: 0.59, 95% CI: 0.37–0.92, p = 0.020). According to protocol analysis which excluded participants using the lotions less than 90% of the time found similar results with no effect from the use of Repellent. Conclusions This randomised controlled trial suggests that topical Repellents are not a suitable intervention in addition to LLINs against malaria amongst agricultural populations in southern Lao PDR. These results are also likely to be applicable to much of the Greater Mekong Sub-region. Trial Registration This trial is registered with number NCT00938379

  • safety of the Insect Repellent n n diethyl m toluamide deet in pregnancy
    American Journal of Tropical Medicine and Hygiene, 2001
    Co-Authors: Rose Mcgready, Katie Hamilton, Julie A Simpson, Thein Cho, Christine Luxemburger, Robert Edwards, Sornchai Looareesuwan, Nicholas J White, Francois Nosten, Steven W Lindsay
    Abstract:

    The safety of daily application of N, N-diethyl-m-toluamide (DEET) (1.7 g of DEET/day) in the second and third trimesters of pregnancy was assessed as part of a double-blind, randomized, therapeutic trial of Insect Repellents for the prevention of malaria in pregnancy (n = 897). No adverse neurologic, gastrointestinal, or dermatologic effects were observed for women who applied a median total dose of 214.2 g of DEET per pregnancy (range = 0-345.1 g). DEET crossed the placenta and was detected in 8% (95% confidence interval = 2.6-18.2) of cord blood samples from a randomly selected subgroup of DEET users (n = 50). No adverse effects on survival, growth, or development at birth, or at one year, were found. This is the first study to document the safety of DEET applied regularly in the second and third trimesters of pregnancy. The results suggest that the risk of DEET accumulating in the fetus is low and that DEET is safe to use in later pregnancy.

Tao Wang - One of the best experts on this subject based on the ideXlab platform.

  • Metabolic Disposition of the Insect Repellent DEET and the Sunscreen Oxybenzone Following Intravenous and Skin Administration in Rats
    2016
    Co-Authors: Daryl J. Fediuk, Tao Wang, Yufei Chen, Fiona E. Parkinson, Michael P. Namaka, Keith J. Simons, Frank J. Burczynski
    Abstract:

    Insect Repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone have shown a synergistic percutaneous enhancement when applied concurrently. Both compounds are extensively metabolized in vivo into a series of potentially toxic metabolites: 2 metabolites of DEET, N,N-diethyl-m-hydroxymethylbenzamide (DHMB) and N-ethyl-m-toluamide (ET), and 3 metabolites of oxybenzone, 2,4-dihydroxybenzophenone (DHB), 2,2-dihydroxy-4-methoxybenzophenone (DMB), and 2,3,4-trihydroxybenzophenone (THB). In this study, the metabolites were extensively distributed following intravenous and topical skin administration of DEET and oxybenzone in rats. Combined application enhanced the disposition of all DEET metabolites in the liver but did not consistently affect the distribution of oxybenzone metabolites. The DHMB appeared to be the major metabolite for DEET, while THB and its precursor DHB were the main metabolites for oxybenzone. Repeated once-daily topical application for 30 days led to higher concentrations of DEET metabolites in the liver. Hepatoma cell studies revealed a decrease in cellular proliferation from all metabolites as single and combined treatments, most notably at 72 hours. Increased accumulation of DHMB and ET in the liver together with an ability to reduce cellular proliferation at achievable plasma concentrations indicated that simultaneous exposure to DEET and oxybenzone might have the potential to precipitate adverse effects in a rat animal model

  • tissue disposition of the Insect Repellent deet and the sunscreen oxybenzone following intravenous and topical administration in rats
    Biopharmaceutics & Drug Disposition, 2011
    Co-Authors: Daryl J. Fediuk, Tao Wang, Yufei Chen, Fiona E. Parkinson, Michael P. Namaka, Keith J. Simons, Frank J. Burczynski
    Abstract:

    The Insect Repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone (OBZ) have been shown to produce synergistic permeation enhancement when applied concurrently in vitro and in vivo. The disposition of both compounds following intravenous administration (2 mg/kg of DEET or OBZ) and topical skin application (100 mg/kg of DEET and 40 mg/kg of OBZ) was determined in male Sprague-Dawley rats. Pharmacokinetic analysis was also conducted using compartmental and non-compartmental methods. A two-compartment model was deemed the best fit for intravenous administration. The DEET and oxybenzone permeated across the skin to accumulate in blood, liver and kidney following topical skin application. Combined use of DEET and oxybenzone accelerated the disappearance of both compounds from the application site, increased their distribution in the liver and significantly decreased the apparent elimination half-lives of both compounds (p < 0.05). Hepatoma cell studies revealed toxicity from exposure to all treatment concentrations, most notably at 72 h. Although DEET and oxybenzone were capable of mutually enhancing their percutaneous permeation and systemic distribution from topical skin application, there was no evidence of increased hepatotoxic deficits from concurrent application. Copyright © 2011 John Wiley & Sons, Ltd.

  • Percutaneous characterization of the Insect Repellent DEET and the sunscreen oxybenzone from topical skin application
    Toxicology and applied pharmacology, 2007
    Co-Authors: Sreeneeranj Kasichayanula, James D House, Tao Wang
    Abstract:

    The synergistic percutaneous enhancement between Insect Repellent DEET and sunscreen oxybenzone has been proven in our laboratory using a series of in vitro diffusion studies. In this study, we carried out an in vivo study to characterize skin permeation profiles from topical skin application of three commercially available Repellent and sunscreen preparations. The correlation between skin disposition and drug metabolism was attempted by using data collected. Both DEET and oxybenzone permeated across the skin after the application and achieved substantial systemic absorption. Combined use of DEET and oxybenzone significantly enhanced the percutaneous penetration percentages (ranging 36-108%) due to mutual enhancement effects. Skin disposition indicated that DEET produced a faster transdermal permeation rate and higher systemic absorption extent, but oxybenzone formed a concentrated depot within the skin and delivered the content slowly over the time. In vivo AUCP/MRT of DEET and oxybenzone was increased by 37%/17% and 63%/10% when the two compounds were used together. No DEET was detected from the urine samples 48 h after the application. Tape stripping seemed to be a satisfactory approach for quantitative assessment of DEET and oxybenzone penetration into the stratum corneum. It was also concluded that pharmacological and toxicological perspectives from concurrent application of Insect Repellent and sunscreen products require further evaluation to ensure use efficacy and safety of these common consumer healthcare products.

  • simultaneous analysis of Insect Repellent deet sunscreen oxybenzone and five relevant metabolites by reversed phase hplc with uv detection application to an in vivo study in a piglet model
    Journal of Chromatography B, 2005
    Co-Authors: Sreeneeranj Kasichayanula, James D House, Tao Wang
    Abstract:

    N,N-Diethyl-m-toluamide (DEET) and oxybenzone are two essential active ingredients in Insect Repellent and sunscreen preparations. We developed and validated a simple, sensitive, and selective HPLC assay to simultaneously measure DEET, oxybenzone and five primary metabolites of DEET and oxybenzone in biological samples including plasma, urine and skin strips. The compounds were separated on a reversed-phase C18 column using three-stage gradient steps with methanol and water. DEET and two relevant metabolites were detected at 254 nm, while oxybenzone and three relevant metabolites were detected at 289 nm. The limit of detection was 0.6 ng for DEET and 0.5 ng for oxybenzone, respectively. The developed method was further applied to analyze various biological samples from an in vivo animal study that evaluated concurrent use of commercially available Insect Repellent and sunscreen preparations.

Frank J. Burczynski - One of the best experts on this subject based on the ideXlab platform.

  • Metabolic Disposition of the Insect Repellent DEET and the Sunscreen Oxybenzone Following Intravenous and Skin Administration in Rats
    2016
    Co-Authors: Daryl J. Fediuk, Tao Wang, Yufei Chen, Fiona E. Parkinson, Michael P. Namaka, Keith J. Simons, Frank J. Burczynski
    Abstract:

    Insect Repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone have shown a synergistic percutaneous enhancement when applied concurrently. Both compounds are extensively metabolized in vivo into a series of potentially toxic metabolites: 2 metabolites of DEET, N,N-diethyl-m-hydroxymethylbenzamide (DHMB) and N-ethyl-m-toluamide (ET), and 3 metabolites of oxybenzone, 2,4-dihydroxybenzophenone (DHB), 2,2-dihydroxy-4-methoxybenzophenone (DMB), and 2,3,4-trihydroxybenzophenone (THB). In this study, the metabolites were extensively distributed following intravenous and topical skin administration of DEET and oxybenzone in rats. Combined application enhanced the disposition of all DEET metabolites in the liver but did not consistently affect the distribution of oxybenzone metabolites. The DHMB appeared to be the major metabolite for DEET, while THB and its precursor DHB were the main metabolites for oxybenzone. Repeated once-daily topical application for 30 days led to higher concentrations of DEET metabolites in the liver. Hepatoma cell studies revealed a decrease in cellular proliferation from all metabolites as single and combined treatments, most notably at 72 hours. Increased accumulation of DHMB and ET in the liver together with an ability to reduce cellular proliferation at achievable plasma concentrations indicated that simultaneous exposure to DEET and oxybenzone might have the potential to precipitate adverse effects in a rat animal model

  • tissue disposition of the Insect Repellent deet and the sunscreen oxybenzone following intravenous and topical administration in rats
    Biopharmaceutics & Drug Disposition, 2011
    Co-Authors: Daryl J. Fediuk, Tao Wang, Yufei Chen, Fiona E. Parkinson, Michael P. Namaka, Keith J. Simons, Frank J. Burczynski
    Abstract:

    The Insect Repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone (OBZ) have been shown to produce synergistic permeation enhancement when applied concurrently in vitro and in vivo. The disposition of both compounds following intravenous administration (2 mg/kg of DEET or OBZ) and topical skin application (100 mg/kg of DEET and 40 mg/kg of OBZ) was determined in male Sprague-Dawley rats. Pharmacokinetic analysis was also conducted using compartmental and non-compartmental methods. A two-compartment model was deemed the best fit for intravenous administration. The DEET and oxybenzone permeated across the skin to accumulate in blood, liver and kidney following topical skin application. Combined use of DEET and oxybenzone accelerated the disappearance of both compounds from the application site, increased their distribution in the liver and significantly decreased the apparent elimination half-lives of both compounds (p < 0.05). Hepatoma cell studies revealed toxicity from exposure to all treatment concentrations, most notably at 72 h. Although DEET and oxybenzone were capable of mutually enhancing their percutaneous permeation and systemic distribution from topical skin application, there was no evidence of increased hepatotoxic deficits from concurrent application. Copyright © 2011 John Wiley & Sons, Ltd.

Sreeneeranj Kasichayanula - One of the best experts on this subject based on the ideXlab platform.

  • Percutaneous characterization of the Insect Repellent DEET and the sunscreen oxybenzone from topical skin application
    Toxicology and applied pharmacology, 2007
    Co-Authors: Sreeneeranj Kasichayanula, James D House, Tao Wang
    Abstract:

    The synergistic percutaneous enhancement between Insect Repellent DEET and sunscreen oxybenzone has been proven in our laboratory using a series of in vitro diffusion studies. In this study, we carried out an in vivo study to characterize skin permeation profiles from topical skin application of three commercially available Repellent and sunscreen preparations. The correlation between skin disposition and drug metabolism was attempted by using data collected. Both DEET and oxybenzone permeated across the skin after the application and achieved substantial systemic absorption. Combined use of DEET and oxybenzone significantly enhanced the percutaneous penetration percentages (ranging 36-108%) due to mutual enhancement effects. Skin disposition indicated that DEET produced a faster transdermal permeation rate and higher systemic absorption extent, but oxybenzone formed a concentrated depot within the skin and delivered the content slowly over the time. In vivo AUCP/MRT of DEET and oxybenzone was increased by 37%/17% and 63%/10% when the two compounds were used together. No DEET was detected from the urine samples 48 h after the application. Tape stripping seemed to be a satisfactory approach for quantitative assessment of DEET and oxybenzone penetration into the stratum corneum. It was also concluded that pharmacological and toxicological perspectives from concurrent application of Insect Repellent and sunscreen products require further evaluation to ensure use efficacy and safety of these common consumer healthcare products.

  • simultaneous analysis of Insect Repellent deet sunscreen oxybenzone and five relevant metabolites by reversed phase hplc with uv detection application to an in vivo study in a piglet model
    Journal of Chromatography B, 2005
    Co-Authors: Sreeneeranj Kasichayanula, James D House, Tao Wang
    Abstract:

    N,N-Diethyl-m-toluamide (DEET) and oxybenzone are two essential active ingredients in Insect Repellent and sunscreen preparations. We developed and validated a simple, sensitive, and selective HPLC assay to simultaneously measure DEET, oxybenzone and five primary metabolites of DEET and oxybenzone in biological samples including plasma, urine and skin strips. The compounds were separated on a reversed-phase C18 column using three-stage gradient steps with methanol and water. DEET and two relevant metabolites were detected at 254 nm, while oxybenzone and three relevant metabolites were detected at 289 nm. The limit of detection was 0.6 ng for DEET and 0.5 ng for oxybenzone, respectively. The developed method was further applied to analyze various biological samples from an in vivo animal study that evaluated concurrent use of commercially available Insect Repellent and sunscreen preparations.

Tina Ilc - One of the best experts on this subject based on the ideXlab platform.

  • The seco-iridoid pathway from Catharanthus roseus
    2016
    Co-Authors: Karel Miettinen, Lemeng Dong, Nicolas Navrot, Thomas Schneider, Vincent Burlat, Jacob Pollier, Lotte Woittiez, Tina Ilc, Robert Verpoorte, Kirsi-marja Oksman-caldentey
    Abstract:

    The (seco)iridoids and their derivatives, the monoterpenoid indole alkaloids (MIAs), form two large families of plant-derived bioactive compounds with a wide spectrum of high-value pharmacological and Insect-Repellent activities. Vinblastine and vincristine, MIAs used as anticancer drugs, are produced by Catharanthus roseus in extremely low levels, leading to high market prices and poor availability. Their biotechnological production is hampered by the fragmentary knowledge of their biosynthesis. Here we report the discovery of the last four missing steps of the (seco)iridoid biosynthesis pathway. Expression of the eight genes encoding this pathway, together with two genes boosting precursor formation and two downstream alkaloid biosynthesis genes, in an alternative plant host, allows the heterologous production of the complex MIA strictosidine. This confirms the functionality of all enzymes of the pathway and highlights their utility for synthetic biology programmes towards a sustainable biotechnological production of valuable (seco)iridoids and alkaloids wit

  • the seco iridoid pathway from catharanthus roseus
    Nature Communications, 2014
    Co-Authors: Karel Miettinen, Lemeng Dong, Nicolas Navrot, Thomas Schneider, Vincent Burlat, Jacob Pollier, Lotte Woittiez, Sander Van Der Krol, Raphael Lugan, Tina Ilc
    Abstract:

    The (seco)iridoids and their derivatives, the monoterpenoid indole alkaloids (MIAs), form two large families of plant-derived bioactive compounds with a wide spectrum of high-value pharmacological and Insect-Repellent activities. Vinblastine and vincristine, MIAs used as anticancer drugs, are produced by Catharanthus roseus in extremely low levels, leading to high market prices and poor availability. Their biotechnological production is hampered by the fragmentary knowledge of their biosynthesis. Here we report the discovery of the last four missing steps of the (seco)iridoid biosynthesis pathway. Expression of the eight genes encoding this pathway, together with two genes boosting precursor formation and two downstream alkaloid biosynthesis genes, in an alternative plant host, allows the heterologous production of the complex MIA strictosidine. This confirms the functionality of all enzymes of the pathway and highlights their utility for synthetic biology programmes towards a sustainable biotechnological production of valuable (seco)iridoids and alkaloids with pharmaceutical and agricultural applications.