scholarly journals Toxicodynamic aspects and new tools for assessing acetaminophen toxicity: a review

Author(s):  
Fernando Wendel Franco ◽  
Maíra Casali Malonn

Acetaminophen (Tylenol®) or APAP is a widely used non-steroidal anti-inflammatory drug responsible for many cases of intoxication, suicide, and liver toxicity. Due to its toxicity mechanisms are not yet fully elucidated and this literature review aims to objectively bring some of the most recent and relevant scientific discoveries that can help in the understanding of the subject. After being ingested, paracetamol is absorbed and begins to be digested in the stomach, then being metabolized by the liver through phase I and phase II (glucuronyltransferases and sulfotransferases). When present in excess in the body, APAP forms an active metabolite known as N-acetyl-para-benzoquinone-imine (NAPQI). This metabolite is a reactive species capable of binding to living cells and proteins causing damages, which are largely responsible for injuries, especially in the liver. As a conclusion of this study, it can be inferred that the lesions caused by acetaminophen, in addition to protein adducts, also extend to mitochondria and proteins. New markers, in addition to enzymes already known from the CYP families, also include proteins and cytokines, in addition to molecular methods, messenger RNA and micro RNA have been used to study hepatotoxicity by APAP. This makes it easier to deeply understand the mechanisms of toxicity induced by acetaminophen and then to advance in studies with new therapies.

Author(s):  
Fernando Wendel Franco ◽  
Maíra Casali Malonn

Paracetamol (Tylenol®) is a widely used non-steroidal anti-inflammatory drug responsible for many cases of intoxication and liver failure. When taken orally, it is absorbed and begins to be digested in the stomach. Paracetamol is primarily metabolized by the liver via phase I and phase II enzymes (glucuronyltransferases and sulfotransferases). When present in excess in the body, it forms an active metabolite known as N-acetyl-para-benzoquinone-imine (NAPQI). This metabolite is a reactive species capable of binding to living cells and proteins causing injuries and adducts, which are largely responsible for damage, especially the liver. The study of paracetamol pharmacokinetics is important to understand its toxicity pathways and thus develop new therapies to prevent or minimize the damage caused by this drug. This review sought some of the most relevant works that address the pharmacokinetics of paracetamol to facilitate a general understanding of what has been discovered so far on the subject. This study also aims to make patients aware of the possible harm that can occur when this drug is indiscriminately used.


2003 ◽  
Vol 3 ◽  
pp. 1332-1343 ◽  
Author(s):  
Tom B. Vree ◽  
Erik Dammers ◽  
Ivan Ulc ◽  
Stefan Horkovics-Kovats ◽  
Miroslav Ryska ◽  
...  

The aim of this pharmacokinetic evaluation was to show the effect of the extra methyl group in simvastatin on esterase hydrolysis between lovastatin and simvastatin in male and female volunteers. This study was based on the plasma concentration-time curves and the pharmacokinetics of lovastatin and simvastatin with its respective active metabolite statin-β-hydroxy acid obtained from two different bioequivalence studies, each with 18 females and 18 males. Results were: 1-The group of female volunteers showed a higher yield of the active metabolite β-hydroxy acid than the group of males (p < 0.002) for both lovastatin and simvastatin. This difference was not related to the body weight of both groups. 2-In the male/female groups, subject-dependent yield of active metabolite β-hydroxy acid was demonstrated, which was independent of the formulation. The variation in plasma/liver hydrolysis resulted in a fan-shaped distribution of data points when the AUCtlovastatin was plotted vs. that of the β-hydroxy acid metabolite. In the fan of data points, subgroups could be distinguished, each showing a different regression line and with a different Y-intercept (AUCtβ-hydroxy acid). 3-Lovastatin hydrolysis was higher than simvastatin hydrolysis. 4-It was possible to discriminate between hydrolysis of both lovastatin and simvastatin by plasma/liver or tissue esterase activity.The three subgroups of subjects (males/females) showing different but high yield of statin β-hydroxy acid can be explained by variable hydrolysis of plasma and hepatic microsomal and cytosolic carboxyesterase activity.This study showed clearly that despite the subject-dependent hydrolysis of lovastatin/simvastatin to the active metabolite, males tend to hydrolyse less than females. The extra methyl group in simvastatin results in less hydrolysis due to steric hindrance.


2009 ◽  
Vol 27 (1) ◽  
pp. 65-92
Author(s):  
Susan Jones

This article explores the diversity of British literary responses to Diaghilev's project, emphasising the way in which the subject matter and methodologies of Diaghilev's modernism were sometimes unexpectedly echoed in expressions of contemporary British writing. These discussions emerge both in writing about Diaghilev's work, and, more discretely, when references to the Russian Ballet find their way into the creative writing of the period, serving to anchor the texts in a particular cultural milieu or to suggest contemporary aesthetic problems in the domain of literary aesthetics developing in the period. Figures from disparate fields, including literature, music and the visual arts, brought to their criticism of the Ballets Russes their individual perspectives on its aesthetics, helping to consolidate the sense of its importance in contributing to the inter-disciplinary flavour of modernism across the arts. In the field of literature, not only did British writers evaluate the Ballets Russes in terms of their own poetics, their relationship to experimentation in the novel and in drama, they developed an increasing sense of the company's place in dance history, its choreographic innovations offering material for wider discussions, opening up the potential for literary modernism's interest in impersonality and in the ‘unsayable’, discussions of the body, primitivism and gender.


2018 ◽  
Vol 27 (1) ◽  
pp. 5-21
Author(s):  
Amanda Dennis

Lying in ditches, tromping through mud, wedged in urns, trash bins, buried in earth, bodies in Beckett appear anything but capable of acting meaningfully on their environments. Bodies in Beckett seem, rather, synonymous with abjection, brokenness, and passivity—as if the human were overcome by its materiality: odours, pain, foot sores, decreased mobility. To the extent that Beckett's personae act, they act vaguely (wandering) or engage in quasi-obsessive, repetitive tasks: maniacal rocking, rotating sucking stones and biscuits, uttering words evacuated of sense, ceaseless pacing. Perhaps the most vivid dramatization of bodies compelled to meaningless, repetitive movement is Quad (1981), Beckett's ‘ballet’ for television, in which four bodies in hooded robes repeat their series ad infinitum. By 1981, has all possibility for intentional action in Beckett been foreclosed? Are we doomed, as Hamm puts it, to an eternal repetition of the same? (‘Moments for nothing, now as always, time was never and time is over, reckoning closed and story ended.’)This article proposes an alternative reading of bodily abjection, passivity and compulsivity in Beckett, a reading that implies a version of agency more capacious than voluntarism. Focusing on Quad as an illustrative case, I show how, if we shift our focus from the body's diminished possibilities for movement to the imbrication of Beckett's personae in environments (a mound of earth), things, and objects, a different story emerges: rather than dramatizing the impossibility of action, Beckett's work may sketch plans for a more ecological, post-human version of agency, a more collaborative mode of ‘acting’ that eases the divide between the human, the world of inanimate objects, and the earth.Movements such as new materialism and object-oriented ontology challenge hierarchies among subjects, objects and environments, questioning the rigid distinction between animate and inanimate, and the notion of the Anthropocene emphasizes the influence of human activity on social and geological space. A major theoretical challenge that arises from such discourses (including 20th-century challenges to the idea of an autonomous, willing, subject) is to arrive at an account of agency robust enough to survive if not the ‘death of the subject’ then its imbrication in the material and social environment it acts upon. Beckett's treatment of the human body suggests a version of agency that draws strength from a body's interaction with its environment, such that meaning is formed in the nexus between body and world. Using the example of Quad, I show how representations of the body in Beckett disturb the opposition between compulsivity (when a body is driven to move or speak in the absence of intention) and creative invention. In Quad, serial repetition works to create an interface between body and world that is receptive to meanings outside the control of a human will. Paradoxically, compulsive repetition in Beckett, despite its uncomfortable closeness to addiction, harnesses a loss of individual control that proposes a more versatile and ecologically mindful understanding of human action.


Author(s):  
Aleksey Klokov ◽  
Evgenii Slobodyuk ◽  
Michael Charnine

The object of the research when writing the work was the body of text data collected together with the scientific advisor and the algorithms for processing the natural language of analysis. The stream of hypotheses has been tested against computer science scientific publications through a series of simulation experiments described in this dissertation. The subject of the research is algorithms and the results of the algorithms, aimed at predicting promising topics and terms that appear in the course of time in the scientific environment. The result of this work is a set of machine learning models, with the help of which experiments were carried out to identify promising terms and semantic relationships in the text corpus. The resulting models can be used for semantic processing and analysis of other subject areas.


Author(s):  
Robert Laumbach ◽  
Michael Gochfeld

This chapter describes the basic principles of toxicology and their application to occupational and environmental health. Topics covered include pathways that toxic substances may take from sources in the environment to molecular targets in the cells of the body where toxic effects occur. These pathways include routes of exposure, absorption into the body, distribution to organs and tissues, metabolism, storage, and excretion. The various types of toxicological endpoints are discussed, along with the concepts of dose-response relationships, threshold doses, and the basis of interindividual differences and interspecies differences in response to exposure to toxic substances. The diversity of cellular and molecular mechanisms of toxicity, including enzyme induction and inhibition, oxidative stress, mutagenesis, carcinogenesis, and teratogenesis, are discussed and the chapter concludes with examples of practical applications in clinical evaluation and in toxicity testing.


Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 794
Author(s):  
Cullen Horstmann ◽  
Victoria Davenport ◽  
Min Zhang ◽  
Alyse Peters ◽  
Kyoungtae Kim

Next-generation sequencing (NGS) technology has revolutionized sequence-based research. In recent years, high-throughput sequencing has become the method of choice in studying the toxicity of chemical agents through observing and measuring changes in transcript levels. Engineered nanomaterial (ENM)-toxicity has become a major field of research and has adopted microarray and newer RNA-Seq methods. Recently, nanotechnology has become a promising tool in the diagnosis and treatment of several diseases in humans. However, due to their high stability, they are likely capable of remaining in the body and environment for long periods of time. Their mechanisms of toxicity and long-lasting effects on our health is still poorly understood. This review explores the effects of three ENMs including carbon nanotubes (CNTs), quantum dots (QDs), and Ag nanoparticles (AgNPs) by cross examining publications on transcriptomic changes induced by these nanomaterials.


2021 ◽  
pp. 097168582110159
Author(s):  
Sital Mohanty ◽  
Subhasis Sahoo ◽  
Pranay Kumar Swain

Science, technology and human values have been the subject of enquiry in the last few years for social scientists and eventually the relationship between science and gender is the subject of an ongoing debate. This is due to the event of globalization which led to the exponential growth of new technologies like assisted reproductive technology (ART). ART, one of the most iconic technological innovations of the twentieth century, has become increasingly a normal social fact of life. Since ART invades multiple human discourses—thereby transforming culture, society and politics—it is important what is sociological about ART as well as what is biological. This article argues in commendation of sociology of technology, which is alert to its democratic potential but does not concurrently conceal the historical and continuing role of technology in legitimizing gender discrimination. The article draws the empirical insights from local articulations (i.e., Odisha state in eastern India) for the understandings of motherhood, freedom and choice, reproductive right and rights over the body to which ART has contributed. Sociologically, the article has been supplemented within the broader perspectives of determinism, compatibilism alongside feminism.


1985 ◽  
Vol 110 (3_Suppla) ◽  
pp. S11-S18 ◽  
Author(s):  
H. Kopera

Metabolism is the term employed to embrace the various physical and chemical processes occurring within the tissues upon which the growth and heat production of the body depend and from which the energy for muscular activity, for the maintenance of vital activity and for the maintenance of vital functions is derived (Best & Taylor 1950). The destructive processes by which complex substances are converted by living cells into more simple compounds are called catabolism. Anabolism denotes the constructive processes by which simple substances are converted by living cells into more complex compounds, especially into living matter. Catabolism and anabolism are part of all metabolic processes, the carbohydrate, fat and protein metabolism. The term anabolic refers only to substances that exert an anabolic effect on protein metabolism and are unlikely to cause adverse androgenic effects. They shift the equilibrium between protein synthesis and degradation in the body as a whole in the direction of synthesis, either by promoting protein synthesis or reducing its breakdown. The protein anabolic effect of anabolic steroids is not restricted to single organs but is the result of stimulated biosynthesis of cellular protein in the whole organism.


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