scholarly journals Differences Between Lovastatin and Simvastatin Hydrolysis in Healthy Male and Female Volunteers: Gut Hydrolysis of Lovastatin is Twice that of Simvastatin

2003 ◽  
Vol 3 ◽  
pp. 1332-1343 ◽  
Author(s):  
Tom B. Vree ◽  
Erik Dammers ◽  
Ivan Ulc ◽  
Stefan Horkovics-Kovats ◽  
Miroslav Ryska ◽  
...  
Keyword(s):  
Hydroxy Acid ◽  
Active Metabolite ◽  
Regression Line ◽  
The Body ◽  
High Yield ◽  
Male And Female ◽  
Methyl Group ◽  
Data Points ◽  
The Subject ◽  
Hydrolysis Of

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.

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

2021 ◽  
pp. 28-38
Author(s):  
Fernando Wendel Franco ◽  
Maíra Casali Malonn
Keyword(s):  
Messenger Rna ◽  
Active Metabolite ◽  
Liver Toxicity ◽  
Living Cells ◽  
The Body ◽  
Micro Rna ◽  
Mechanisms Of Toxicity ◽  
Acetaminophen Toxicity ◽  
The Subject ◽  
Toxicity Mechanisms

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.

scholarly journals Lack of Male-Female Differences in Disposition and Esterase Hydrolysis of Ramipril to Ramiprilat in Healthy Volunteers after a Single Oral Dose

2003 ◽  
Vol 3 ◽  
pp. 1344-1358
Author(s):  
Tom B. Vree ◽  
Erik Dammers ◽  
Ivan Ulc ◽  
Stefan Horkovics-Kovats ◽  
Miroslav Ryska ◽  
...  
Keyword(s):  
Body Weight ◽  
Plasma Concentration ◽  
Active Metabolite ◽  
Plasma Concentrations ◽  
Parent Drug ◽  
Male And Female ◽  
Concentration Time ◽  
Males And Females ◽  
The Difference ◽  
Hydrolysis Of

The objective of this study was to identify differences in disposition and esterase hydrolysis of ramipril between male and female volunteers. Plasma concentration and area under the concentration-time curve until the last measured concentration (AUCt) data of ramipril and its active metabolite ramiprilat (-diacid) were obtained from a randomised, cross-over bioequivalence study in 36 subjects (18 females and 18 males). Participants received a single 5-mg oral dose of two different formulations of ramipril (Formulation I and II). Plasma ramipril and ramiprilat concentrations were determined according to validated methods involving liquid chromatography-mass spectrometry. A total number of 2 � 34 available plasma concentration-time curves of both the parent drug and the metabolite could be analysed, and variations (50�100% coefficient of variation [CV]) in plasma concentrations of both parent drug and metabolite were found. With both the formulations, the mean plasma concentrations-time curves of males and females were identical. The groups of female and male volunteers showed similar yields (AUCt = mg.h/L) of the metabolite ramiprilat (p = 0.37); however, females showed a higher AUCt/kg than males (p = 0.046). This difference was solely attributed to the difference in body weight between males and females (p = 0.00049). In both male and female groups, a subject-dependent yield of active metabolite ramiprilat was demonstrated, which was independent of the formulation.There is a large variation in the ramiprilat t1/2β(50�60% CV). There is a group of subjects who showed a t1/2βof approximately 80 h (15% CV), and two apparent groups with a longer t1/2βfor each formulation (124 h, 22.5% CV; 166 h, 21.6% CV, respectively, p = 0.0013). This variation in the terminal half-life of ramiprilat is not sex related. In all three groups of half-lives, the corresponding Cmax values (mean � SD) of ramiprilat in males and females were identical. Thus, with identical Cmaxand half-lives, the difference found in the AUCt/kg of ramiprilat must be due to the difference in dose, as the consequence of the difference in body weight, following a standard dose of 5 mg in both males and females.This study showed clearly that despite subject-dependent hydrolysis of ramipril to the active metabolite ramiprilat, the variability in the rate of hydrolysis between males and females is similar. With a fixed dose (5 mg), females received a higher dose/kg than males and consequently showed a higher AUCt/kg of the active metabolite ramiprilat.

scholarly journals Acetaminophen pharmacokinetic and toxicological aspects: a review

2021 ◽  
pp. 18-27
Author(s):  
Fernando Wendel Franco ◽  
Maíra Casali Malonn
Keyword(s):  
Liver Failure ◽  
Phase I ◽  
Phase Ii ◽  
Active Metabolite ◽  
Living Cells ◽  
The Body ◽  
Phase Ii Enzymes ◽  
Benzoquinone Imine ◽  
The Subject ◽  
Toxicity Pathways

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.

scholarly journals Calibration and Validation of an Experimental Setup for the Measurement of the Cylindrical Body Shapes and Curvatures of the Objects and Subjects through the Techniques of Rasterstereography

2019 ◽  
Vol 38 (1) ◽  
pp. 197-208
Author(s):  
Majeed Ahmed ◽  
Syed Anwar Ali Zaidi
Keyword(s):  
Regression Line ◽  
Cylindrical Body ◽  
The Body ◽  
Reference Plane ◽  
Experimental Setup ◽  
Body Parts ◽  
Accuracy And Precision ◽  
The Subject ◽  
Body Shapes ◽  
Different Diameters

The intent of study is to establish a criterion for the experimental setup of rasterstereography, one that is more efficient, simple, accurate and precise to examine and analyse the curvature of the object or the subject. Firstly, the setup is needed to be calibrated and for this purpose we considered a reference plane, eleven cylinders of different diameter ranging from 30-119mm were used for calibration of curvature maps of cylinders and cylindrical objects through the regression line. Further this model was tested on subjects and for that we reckoned cylindrical body parts of boys and a total of 30 college students were involved as subjects in this process. The body parts to be measured had curvature like cylinders of different diameters ranging from 42-120mm. The distortion of raster grid was observed, quantified and recorded with the help of different tools and results were established. The regression line was obtained between the measured (x) and computed (y). The standard error of the cylindrical object was 0..04 and that of cylindrical body parts of subjects was 0.0407. This technique was validated through the coefficient of correlation for objects and subjects which was found to be 0.99982 and 0.999141 respectively. Accuracy and Precision were also calculated for this model, which were 99.60% accurate and 99.49% precise. Curvature maps were found more than 99%. This technique is inexpensive, reliable, reproducible and may be installed easily in hospitals to examine appraise body shape, composition and deformities of young men.

scholarly journals Moda i semiotika roda

2016 ◽  
Vol 10 (4) ◽  
pp. 839
Author(s):  
Iva Jestratijević
Keyword(s):  
Cultural Identity ◽  
Gender Norms ◽  
The Body ◽  
Gender Identification ◽  
Special Significance ◽  
Male And Female ◽  
Gender Category ◽  
The Subject ◽  
The Stability

Contemporary studies of fashion interpret articles of clothing as text, through which a specific cultural identity is constructed and expressed. As identities are momentarily realized through the performative act of identifying with a real or ideal subject, fashion has a special significance in every visual creation of a subject as the identity of a given role. In accordance with this, the dressing of the body is viewed as one of the available means of gender identification, as well as a way to confirm the subject through the performing of the assigned role of man and woman. Seeing as the performance of a certain role, in this specific case, entails the existence of the subject as event (of a textual) role, the sphere of clothing fashion is in this paper primarily connected to the sphere of representing the subject as member of a gender category. Clothing is viewed as one in a slew of instruments of gender naturalization, in the sense of the power which clothing has for upholding, performing and displaying the stability of gender norms. Hence, this paper will consider always current issues of the existence of established boundaries of male and female fashion, male and female clothing ornaments and colors, as well as socially acceptable male and female forms of clothing.

SENSITIVITAS ETIS MAHASISWA ATAS PENGGELAPAN PAJAK

2017 ◽  
Vol 8 (2) ◽  
pp. 178-195
Author(s):  
Nurma Risa
Keyword(s):  
Tax Evasion ◽  
Female Students ◽  
T Test ◽  
Study Program ◽  
Male And Female ◽  
Political Sciences ◽  
Significant Difference ◽  
The Subject ◽  
And Gender ◽  
Management Students

This study aims to prove that there is a difference of perception about ethics on tax evasion in UNISMA Bekasi students, based on selected study program and gender. The sample of this research is the students who have fulfilled the subject of taxation, at the Faculty of Economics (FE) and Faculty of Social and Political Sciences (FISIP). Using independent t-test, the results showed that there was no significant difference of perception about tax evasion ethics between FE and FISIP students. But significant differences the perception of tax evasion ethics occur between accounting and management students at FE. Significant differences also did not occur between male and female students

Diaghilev and British Writing

2009 ◽  
Vol 27 (1) ◽  
pp. 65-92
Author(s):  
Susan Jones
Keyword(s):  
Visual Arts ◽  
The Body ◽  
The Novel ◽  
Literary Responses ◽  
Literary Aesthetics ◽  
Ballets Russes ◽  
The Arts ◽  
The Subject ◽  
And Gender ◽  
Opening Up

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.

Compulsive Bodies, Creative Bodies: Beckett'sQuadand Agency in the 21stCentury

2018 ◽  
Vol 27 (1) ◽  
pp. 5-21
Author(s):  
Amanda Dennis
Keyword(s):  
Human Action ◽  
The Body ◽  
New Materialism ◽  
Illustrative Case ◽  
Repetitive Movement ◽  
Repetitive Tasks ◽  
The Subject ◽  
Object Oriented Ontology ◽  
Geological Space ◽  
Alternative Reading

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.

Predicting the citation and impact factor of terms for scientific publications using machine learning algorithms

2020 ◽  
Author(s):  
Aleksey Klokov ◽  
Evgenii Slobodyuk ◽  
Michael Charnine
Keyword(s):  
Machine Learning ◽  
Semantic Processing ◽  
The Body ◽  
Machine Learning Algorithms ◽  
Scientific Publications ◽  
Text Data ◽  
Semantic Relationships ◽  
Subject Areas ◽  
The Subject ◽  
Scientific Environment

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.

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