scholarly journals Ubiquitous presence of paracetamol in human urine: sources and implications

Reproduction ◽  
2014 ◽  
Vol 147 (4) ◽  
pp. R105-R117 ◽  
Author(s):  
Hendrik Modick ◽  
Tobias Weiss ◽  
Georg Dierkes ◽  
Thomas Brüning ◽  
Holger M Koch

N-acetyl-4-aminophenol (acetaminophen/paracetamol, NA4AP) is one of the most commonly used over-the-counter analgesic and antipyretic drugs. Recent studies have reported anti-androgenic effects of NA4AP in vitro and possible associations between intrauterine exposure to NA4AP and the development of male reproductive disorders in humans. NA4AP is also a major metabolite of aniline (phenylamine), representing 75–86% of the aniline dose excreted in urine. Aniline is an important large-volume intermediate in several industrial processes. Besides individuals in various occupational settings with aniline exposure, the general population is also known to be ubiquitously exposed to aniline. In this article, we provide an overview of the recent literature concerning the intake of NA4AP during pregnancy and the possible anti-androgenic effects of NA4AP as well as literature concerning its known metabolic precursor aniline. We also present new research data, including the first human biomonitoring data on NA4AP excretion in urine, showing ubiquitous NA4AP body burdens in the general population at a wide range of concentrations. We found a small but significant impact of smoking on urinary NA4AP concentrations. We further present preliminary data on NA4AP excretion after therapeutic acetaminophen use, after aniline exposure in an occupational setting, and during a controlled fasting study (excluding oral exposure to both aniline and acetaminophen). Our findings indicate exposure to aniline (or aniline-releasing substances) as well as nutrition (next to the direct use of acetaminophen as medication) as possible sources of internal body burdens of NA4AP.

Author(s):  
Armen Nersesyan ◽  
◽  
Miroslav Mišík ◽  
Andriy Cherkas ◽  
Viktoria Serhiyenko ◽  
...  

Introduction. Micronuclei (MN) are small extranuclear DNA-containing structures that are formed as a consequence of structural and numerical chromosomal aberrations. The advantage of MN experiments compared to conventional chromosomal analyses in metaphase cells is that the scoring is by far less time consuming and laborious. MN experiments are currently widely used for the routine screening of chemicals in vitro and in vivo but also for environmental control and human biomonitoring Objectives. The purpose of this review was to collect data on the use of MN experiments for the detection of increased cancer risks as a consequence of environmental, lifestyle and occupational exposures and the detection/diagnosis of different forms of cancer. Methods. Analysis of the literature on methods for MN experiments with humans; as well as the use of this technique in different areas of research. Results. To date, a wide range of protocols for human biomonitoring studies has been developed for the measurement of MN formation in peripheral blood cells and in epithelial from different organs (buccal and nasal cavity, cervix and bladder). In addition to MN, other nuclear anomalies can be scored which reflect genetic instability as well as acute toxicity and the division of target cells. Conclusions. The evidence is accumulating that MN can be used as a diagnostic tool for the detection of increased cancer risks as well as for the early diagnosis of cervical and bladder cancer


2013 ◽  
Vol 6 (3) ◽  
pp. 263-272 ◽  
Author(s):  
G.S. Eriksen ◽  
A. Moldes-Anaya ◽  
C.K. Fæste

Penitrem A is a mycotoxin mainly produced by Penicillium crustosum, a fungal species occurring in all climate zones, ranging from tropical to arctic areas. P. crustosum produces a wide range of toxic metabolites, including penitrems, thomitrems and roquefortine C. The major metabolite, penitrem A, has been associated with several episodes of mycotoxicosis in dogs. The clinical symptoms of acute penitrem A intoxication include classical signs of neurotoxicity, such as tremors, convulsions, ataxia and nystagmus. The outcomes of penitrem A intoxication in animals range from total recovery to death, depending mainly on the level of exposure. Cases of suspected human mycotoxicosis following exposure to P. crustosum infected food, beer or inhalation of dust have also been reported. The toxicokinetics of penitrem A is scarcely studied. The toxin is rapidly absorbed, as demonstrated by the rapid onset of symptoms after exposure, but the absorption has not been quantified. Penitrem A is transported systemically after absorption and has been found in liver, kidney and brain as well as in serum and the gastrointestinal tract in exposed animals. Five phase I metabolites have been found in liver extracts of mice 60 min after oral exposure to penitrem A, while three metabolites were found after in vitro incubations with primary rat hepatocytes and rat liver microsomes. Only penitrem A was found in the brains of exposed mice or intoxicated dogs. The elimination has not been studied. Penitrem A is probably the main tremorgenic compound in Penicillium-infected food and feed commodities, since analogues had lower toxic potentials in comparative studies. Penitrem A affects the central as well as the peripheral nervous system. The toxin blocks the high-conductance Ca2+-activated potassium channels (BK) and impairs the GABAergic neurotransmission in the cerebellum. Animal poisoning by penitrem A is probably underdiagnosed due to a lack of knowledge among veterinarians.


Marine Drugs ◽  
2021 ◽  
Vol 19 (9) ◽  
pp. 476 ◽  
Author(s):  
Marzia Vasarri ◽  
Anna Maria De Biasi ◽  
Emanuela Barletta ◽  
Carlo Pretti ◽  
Donatella Degl’Innocenti

Posidonia oceanica (L.) Delile is a Mediterranean-endemic angiosperm often described for its great ecological importance. Despite evidence of a millennia-old relationship between P. oceanica and humans, as well as traditional medicine applications, the potential benefits of P. oceanica for human health have been documented only recently. This review aims to compile newly acquired knowledge on P. oceanica bioactive properties that allow the scientific community to look at this plant as a promising source of natural therapeutical products for human health. Experimental investigations conducted in both in vitro cellular-based and in vivo animal models pave the way for new research projects aiming at the development of alternative and complementary therapeutic strategies based on P. oceanica against a wide range of pathological conditions.


2020 ◽  
Vol 10 (4) ◽  
pp. 316-321
Author(s):  
Aafaq Khan ◽  
Naveed Faraz ◽  
Faisal Hanif ◽  
Mahpara Mumtaz

Probiotics are essential in human physiology. They play a vital role in providing immunity, producing Vitamin K, relieving lactose intolerance and shortening diarrhea. Besides; it promises the management of Atopy and other incurable conditions. Not only for humans but probiotics are also beneficial for other species including marine and cattle due to the Ecophysiological responses. Unfortunately, probiotics are much neglected by the wide use of antibiotics and other drugs which not only disturbs but kills them completely. As a result; an individual is more vulnerable to a wide range of critical conditions that could have been avoided otherwise. These potential benefits of probiotics require much attention of the healthy consumer while in the main market for over the counter remedies. To prove these effects in treating and preventing particular diseases and increase the acceptance of probiotics by the general population more clinical studies should be conducted in this area


1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.


1997 ◽  
Vol 77 (04) ◽  
pp. 725-729 ◽  
Author(s):  
Mario Colucci ◽  
Silvia Scopece ◽  
Antonio V Gelato ◽  
Donato Dimonte ◽  
Nicola Semeraro

SummaryUsing an in vitro model of clot lysis, the individual response to a pharmacological concentration of recombinant tissue plasminogen activator (rt-PA) and the influence on this response of the physiological variations of blood parameters known to interfere with the fibrinolytic/thrombolytic process were investigated in 103 healthy donors. 125I-fibrin labelled blood clots were submersed in autologous plasma, supplemented with 500 ng/ml of rt-PA or solvent, and the degree of lysis was determined after 3 h of incubation at 37° C. Baseline plasma levels of t-PA, plasminogen activator inhibitor 1 (PAI-1), plasminogen, α2-anti-plasmin, fibrinogen, lipoprotein (a), thrombomodulin and von Willebrand factor as well as platelet and leukocyte count and clot retraction were also determined in each donor. rt-PA-induced clot lysis varied over a wide range (28-75%) and was significantly related to endogenous t-PA, PAI-1, plasminogen (p <0.001) and age (p <0.01). Multivariate analysis indicated that both PAI-1 antigen and plasminogen independently predicted low response to rt-PA. Surprisingly, however, not only PAI-1 but also plasminogen was negatively correlated with rt-PA-ginduced clot lysis. The observation that neutralization of PAI-1 by specific antibodies, both in plasma and within the clot, did not potentiate clot lysis indicates that the inhibitor, including the platelet-derived form, is insufficient to attenuate the thrombolytic activity of a pharmacological concentration of rt-PA and that its elevation, similarly to the elevation of plasminogen, is not the cause of clot resistance but rather a coincident finding. It is concluded that the in vitro response of blood clots to rt-PA is poorly influenced by the physiological variations of the examined parameters and that factors other than those evaluated in this study interfere with clot dissolution by rt-PA. In vitro clot lysis test might help to identify patients who may be resistant to thrombolytic therapy.


Growth regulators, phytohormones, both natural and artificial, are the main means to control plant ontogenesis. They are involved in regulating the processes of cell differentiation and cell divisions, the formation of tissues and organs, the changes in the rate of growth and development, the duration of the certain stages of ontogenesis. The main classes of phytohormones used in plant biotechnology, in particular, in the induction of haploid structures, are auxins and cytokinins. The mechanism of action of phytohormones on a cell is rather complicated and may have a different character. Understanding the characteristics of the action of phytohormones is complicated by the fact that the system of hormonal regulation of plant life is multicomponent. This is manifested in the fact that the same physiological process is most often influenced not by one, but by several phytohormones, covering a wide range of aspects of cell metabolism. In connection with the foregoing, the purpose of our work was to test a set of nutrient media with different basic composition and different proportions of phytohormones to determine the patterns of their influence on the processes of haploid structure induction in rape anther culture using accessions, developed at the Institute of Oilseed Crops NAAS. The material used was two accessions of winter rapeseed (No. 1 and No. 2) and one sample of spring rapeseed, provided by the Rapeseed Breeding laboratory of the Institute of Oilseed Crops. Incised inflorescences were kept against the background of low temperature of 6–8 ° C for several days, and then, under aseptic conditions, anthers with unripe pollen grains were isolated and planted on nutrient media differing in both basic mineral composition and content of phytohormones. MS (Murashige & Skoog 1962) and B5 (Gamborg et al 1968) media were used as basic media. Phytohormones were added to the basic media in various combinations – BA, 2,4-D, NAA at the concentrations of 0.1-0.6 mg/l. In each treatment up to 300 anthers were cultivated. Differences between treatments were evaluated using standard t-test. Studies have shown that in the anther culture of rapeseed on the tested nutrient media, morphogenic structures of different types (embryoids and callus) were originated. Synthetic auxin 2,4-D, regardless of the composition of the basic medium, caused the formation of structures of both types, though with a low frequency. Phytohormone BA of the cytokinin type had a similar effect. In this case, the frequency of structures was slightly higher, and the developed structures were represented mainly by embryoids. The joint action of cytokinin and auxin was the most favorable for the initiation of morphogenic structures. Such combination of phytohormones caused the formation of these structures with a frequency of 24.5-14.7% in the studied genotypes of winter rape. A similar effect of phytohormones on the induction and development of morphogenic structures was also observed in spring rape. In this case, a single basic MS medium was used. The experiment included treatments where phytohormones were absent (control), as well as various combinations of auxin and cytokinin. In the control treatment, the formation of new structures was not noted. In treatments with phytohormones, in addition to the medium with the combination of auxin and cytokinin, the medium in which only cytokinin was present was also rather effective. The treatment in which the action of auxin 2,4-D was combined with the action of another auxin, NAA, turned out to be practically ineffective. Thus, it was found that for the induction of morphogenic structures from microspores in rape anther culture of the tested genotypes, the combination of cytokinin with auxin, or the use of only single cytokinin BA without other phytohormones, had the most positive effect.


Author(s):  
Roohi Mohi-ud-din ◽  
Reyaz Hassan Mir ◽  
Prince Ahad Mir ◽  
Saeema Farooq ◽  
Syed Naiem Raza ◽  
...  

Background: Genus Berberis (family Berberidaceae), which contains about 650 species and 17 genera worldwide, has been used in folklore and various traditional medicine systems. Berberis Linn. is the most established group among genera with around 450-500 species across the world. This comprehensive review will not only help researchers for further evaluation but also provide substantial information for future exploitation of species to develop novel herbal formulations. Objective: The present review is focussed to summarize and collect the updated review of information of Genus Berberis species reported to date regarding their ethnomedicinal information, chemical constituents, traditional/folklore use, and reported pharmacological activities on more than 40 species of Berberis. Conclusion: A comprehensive survey of the literature reveals that various species of the genus possess various phytoconstituents mainly alkaloids, flavonoid based compounds isolated from different parts of a plant with a wide range of pharmacological activities. So far, many pharmacological activities like anti-cancer, anti-hyperlipidemic, hepatoprotective, immunomodulatory, anti-inflammatory both in vitro & in vivo and clinical study of different extracts/isolated compounds of different species of Berberis have been reported, proving their importance as a medicinal plant and claiming their traditional use.


2020 ◽  
Vol 21 (2) ◽  
pp. 97-109 ◽  
Author(s):  
Ana P. dos Santos ◽  
Tamara G. de Araújo ◽  
Gandhi Rádis-Baptista

Venom-derived peptides display diverse biological and pharmacological activities, making them useful in drug discovery platforms and for a wide range of applications in medicine and pharmaceutical biotechnology. Due to their target specificities, venom peptides have the potential to be developed into biopharmaceuticals to treat various health conditions such as diabetes mellitus, hypertension, and chronic pain. Despite the high potential for drug development, several limitations preclude the direct use of peptides as therapeutics and hamper the process of converting venom peptides into pharmaceuticals. These limitations include, for instance, chemical instability, poor oral absorption, short halflife, and off-target cytotoxicity. One strategy to overcome these disadvantages relies on the formulation of bioactive peptides with nanocarriers. A range of biocompatible materials are now available that can serve as nanocarriers and can improve the bioavailability of therapeutic and venom-derived peptides for clinical and diagnostic application. Examples of isolated venom peptides and crude animal venoms that have been encapsulated and formulated with different types of nanomaterials with promising results are increasingly reported. Based on the current data, a wealth of information can be collected regarding the utilization of nanocarriers to encapsulate venom peptides and render them bioavailable for pharmaceutical use. Overall, nanomaterials arise as essential components in the preparation of biopharmaceuticals that are based on biological and pharmacological active venom-derived peptides.


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