Effect of Application Amounts on In Vitro Dermal Absorption Test Using Caffeine and Testosterone.
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ABSTRACT:
SUBMITTER: Im JE
PROVIDER: S-EPMC8147129 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:This guidance on the assessment of dermal absorption has been developed to assist notifiers, users of test facilities and Member State authorities on critical aspects related to the setting of dermal absorption values to be used in risk assessments of active substances in Plant Protection Products (PPPs). It is based on the 'scientific opinion on the science behind the revision of the guidance document on dermal absorption' issued in 2011 by the EFSA Panel on Plant Protection Products and their Residues (PPR). The guidance refers to the EFSA PPR opinion in many instances. In addition, the first version of this guidance, issued in 2012 by the EFSA PPR Panel, has been revised in 2017 on the basis of new available data on human in vitro dermal absorption for PPPs and wherever clarifications were needed. Basic details of experimental design, available in the respective test guidelines and accompanying guidance for the conduct of studies, have not been addressed but recommendations specific to performing and interpreting dermal absorption studies with PPPs are given. Issues discussed include a brief description of the skin and its properties affecting dermal absorption. To facilitate use of the guidance, flow charts are included. Guidance is also provided, for example, when there are no data on dermal absorption for the product under evaluation. Elements for a tiered approach are presented including use of default values, data on closely related products, in vitro studies with human skin (regarded to provide the best estimate), data from experimental animals (rats) in vitro and in vivo, and the so called 'triple pack' approach. Various elements of study design and reporting that reduce experimental variation and aid consistent interpretation are presented. A proposal for reporting data for assessment reports is also provided. The issue of nanoparticles in PPPs is not addressed. Data from volunteer studies have not been discussed since their use is not allowed in EU for risk assessment of PPPs.
| S-EPMC7010093 | biostudies-literature
Project description:Decreased H3K27 deacetylation after KGN cell was treated with 10 um testosterone for 24 h.
2024-08-19 | GSE272605 | GEO
Project description:testosterone application induced H3K27 deacetylation
| PRJNA1137417 | ENA
Project description:BackgroundCaffeine is one of the most commonly used psychoactive drugs in the world, and provides many health benefits including alertness, improved memory, and reducing inflammation. Despite these benefits, caffeine has been implicated in a number of adverse health outcomes possibly due to effects within the endocrine system, effects that may contribute to impaired reproductive function and low testosterone in men. Previous studies have investigated associations between caffeine consumption and testosterone levels in men, although the quantity and generalizability of these studies is lacking, and the results between studies are conflicting and inconclusive.MethodsUsing data from a cross-sectional study of 372 adult men in the 2013-2014 NHANES survey cycle, the researchers set out to characterize the association between serum testosterone levels, caffeine, and 14 caffeine metabolites.ResultsMultivariable, weighted linear regression revealed a significant inverse association between caffeine and testosterone. Multivariable, linear regression revealed significant, inverse associations between 6 xanthine metabolic products of caffeine and testosterone. Inverse associations were observed between 5-methyluric acid products and testosterone, as well as between 5-acetlyamino-6-amino-3-methyluracil and testosterone. A significant, positive association was observed for 7-methyl xanthine, 3,7-dimethyluric acid, and 7-methyluric acid. Logistic regression models to characterize the association between 2 biologically active metabolites of caffeine (theobromine and theophylline) and odds of low testosterone (< 300 ng/dL) were non-significant.ConclusionsThese findings suggest a potential role for caffeine's contribution to the etiology of low testosterone and biochemical androgen deficiency. Future studies are warranted to corroborate these findings and elucidate biological mechanisms underlying this association.
| S-EPMC9112543 | biostudies-literature
Project description:A common dermal exposure assessment strategy estimates the systemic uptake of chemical in contact with skin using the fixed fractional absorption approach: the dermal absorbed dose is estimated as the product of exposure and the fraction of applied chemical that is absorbed, assumed constant for a given chemical. Despite the prominence of this approach there is little guidance regarding the evaluation of experiments from which fractional absorption data are measured. An analysis of these experiments is presented herein, and limitations to the fixed fractional absorption approach are discussed. The analysis provides a set of simple algebraic expressions that may be used in the evaluation of finite dose dermal absorption experiments, affording a more data-driven approach to dermal exposure assessment. Case studies are presented that demonstrate the application of these tools to the assessment of dermal absorption data.
| S-EPMC3868874 | biostudies-other
Project description:PurposeNo study has assessed the acute effect of caffeine supplementation on 100-m sprint running in athletics and caffeine's net ergogenicity on 100-m sprint running remains unclear. We investigated the acute effects of caffeine supplementation on 100-m sprint running performance in a field test.MethodsThirteen male collegiate sprinters were subjected to 100-m sprint running time trials (TT) after the ingestion of 6 mg·kg -1 body weight caffeine or placebo supplementation in a double-blind, counterbalanced, randomized, and crossover design. Sprint velocity was measured with a laser system, and sprint time was calculated from the data in which the effects of environmental factors that would act as confounding factors on sprint time during TT were eliminated.ResultsThe corrected 100-m sprint time was significantly shortened by 0.14 s with caffeine supplementation compared with placebo (placebo: 11.40 ± 0.39 s, caffeine: 11.26 ± 0.33 s; P = 0.007, g = -0.33). The corrected sprint time up to 60 m during TT was also significantly shorter with caffeine supplementation than with placebo ( P = 0.002). Furthermore, the mean sprint velocity for splits of 0-10 and 10-20 m was significantly increased by caffeine supplementation (all P < 0.05).ConclusionsAcute caffeine supplementation enhanced the corrected 100-m sprint time by improving the sprint performance in the first 60 m after more explosive acceleration in the early stage of the acceleration phase. Thus, for the first time, we directly demonstrated caffeine's ergogenicity on 100-m sprint performance in athletics.
| S-EPMC9924959 | biostudies-literature
Project description:BackgroundInfectious disease, particularly the fungal disease chytridiomycosis (caused by Batrachochytrium dendrobatidis), is a primary cause of amphibian declines and extinctions worldwide. The transdermal route, although offering a simple option for drug administration in frogs, is complicated by the lack of knowledge regarding percutaneous absorption kinetics. This study builds on our previous studies in frogs, to formulate and predict the percutaneous absorption of a drug for the treatment of infectious disease in frogs. Chloramphenicol, a drug with reported efficacy in the treatment of infectious disease including Batrachochytrium dendrobatidis, was formulated with 20% v/v propylene glycol and applied to the ventral pelvis of Rhinella marina for up to 6 h. Serum samples were taken during and up to 18 h following exposure, quantified for chloramphenicol content, and pharmacokinetic parameters were estimated using non-compartmental analysis.ResultsSerum levels of chloramphenicol reached the minimum inhibitory concentration (MIC; 12.5 μg.mL- 1) for Batrachochytrium dendrobatidis within 90-120 min of exposure commencing, and remained above the MIC for the remaining exposure time. Cmax (17.09 ± 2.81 μg.mL- 1) was reached at 2 h, while elimination was long (t1/2 = 18.68 h).ConclusionsThe model, based on in vitro data and adjusted for formulation components and in vivo data, was effective in predicting chloramphenicol flux to ensure the MIC for Batrachochytrium dendrobatidis was reached, with serum levels being well above the MICs for other common bacterial pathogens in frogs. Chloramphenicol's extended elimination means that a 6-h bath may be adequate to maintain serum levels for up to 24 h. We suggest trialling a reduction of the currently-recommended continuous (23 h/day for 21-35 days) chloramphenicol bathing for chytrid infection with this formulation.
| S-EPMC7842057 | biostudies-literature
Project description:The objective of this paper is to describe general approaches of diagnostic test accuracy (DTA) that are available for the quantitative synthesis of data using R software. We conduct a DTA that summarizes statistics for univariate analysis and bivariate analysis. The package commands of R software were "metaprop" and "metabin" for sensitivity, specificity, and diagnostic odds ratio; forest for forest plot; reitsma of "mada" for a summarized receiver-operating characteristic (ROC) curve; and "metareg" for meta-regression analysis. The estimated total effect sizes, test for heterogeneity and moderator effect, and a summarized ROC curve are reported using R software. In particular, we focus on how to calculate the effect sizes of target studies in DTA. This study focuses on the practical methods of DTA rather than theoretical concepts for researchers whose fields of study were non-statistics related. By performing this study, we hope that many researchers will use R software to determine the DTA more easily, and that there will be greater interest in related research.
| S-EPMC6545496 | biostudies-literature
Project description:BackgroundThe variable clinical presentation of malignant hyperthermia (MH), a disorder of calcium signalling, hinders its diagnosis and management. Diagnosis relies on the caffeine-halothane contracture test, measuring contraction forces upon exposure of muscle to caffeine or halothane (FC and FH, respectively). Patients with above-threshold FC or FH are diagnosed as MH susceptible. Many patients test positive to halothane only (termed 'HH'). Our objective was to determine the characteristics of these HH patients, including their clinical symptoms and features of cytosolic Ca2+ signalling related to excitation-contraction coupling in myotubes.MethodsAfter institutional ethics committee approval, recruited patients undergoing contracture testing at Toronto's MH centre were assigned to three groups: HH, doubly positive (HS), and negative patients (HN). A clinical index was assembled from musculoskeletal symptoms and signs. An analogous calcium index summarised four measures in cultured myotubes: resting [Ca2+]cytosol, frequency of spontaneous cytosolic Ca2+ events, Ca2+ waves, and cell-wide Ca2+ spikes after electrical stimulation.ResultsThe highest values of both indexes were found in the HH group; the differences in calcium index between HH and the other groups were statistically significant. The principal component analysis confirmed the unique cell-level features of the HH group, and identified elevated resting [Ca2+]cytosol and spontaneous event frequency as the defining HH characteristics.ConclusionsThese findings suggest that HH pathogenesis stems from excess Ca2+ leak through sarcoplasmic reticulum channels. This identifies HH as a separate diagnostic group and opens their condition to treatment based on understanding of pathophysiological mechanisms.
| S-EPMC6334558 | biostudies-literature
Project description:Percutaneous absorption is highly variable between chemicals but also within chemicals depending on exposure conditions and experimental set up. We tested a larger number of organic solvents with the same experimental set up, using skin from new-born piglets and static diffusion cells. Thirty-six common organic solvents were studied neat (and 31 of them also in water dilution): acetone, acetonitrile, n-butanol 2-butanone 2-butoxyethanol, 1-butoxy-2-propanol, n-butyl acetate, butyl acrylate, cyclohexane, cyclohexanone, 1,2-dichloroethane, dichloromethane, ethanol, 2-ethoxyethanol, ethyl acetate, ethyl acrylate, ethylbenzene, furfuryl alcohol, n-hexane, 2-hexanone, 2-isopropoxyethanol, methanol, 1-methoxy-2-propanol, methyl acrylate, 3-methyl-1-butanol, methyl tertiary butyl ether, 4-metyl-2-pentanol, methyl methacrylate, 2-propanol, 2-propen-1-ol, 2-propoxyethanol, 1-propoxy-2-propanol, styrene, trichloromethane, toluene and m-xylene. In addition, a mixture of 2-methylbutyl acetate and n-pentyl acetate was tested. For most of the solvents, little or no percutaneous absorption data have been published. Lag times, steady-state fluxes and apparent permeability coefficients were obtained from the time courses of solvent appearance in the receptor medium, as measured by gas chromatography. The use of the same methodology and kind of skin resulted in small variability within experiments, underlining the need for consistent methodology for useful results for developing predictive models. Furthermore, a comparison of the neat and diluted data shows that water dilution affects all these variables and that the direction and magnitude of the effects vary between chemicals. This comparison strongly supports that prediction of percutaneous absorption of neat and water diluted chemicals requires different models.
| S-EPMC6209206 | biostudies-literature