15,848 research outputs found

    Pharmacokinetic and pharmacodynamic evaluation of raltegravir and experience from clinical trials in HIV-positive patients

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    Raltegravir was the first available integrase inhibitor for treating HIV-positive patients. This review aims to provide an overview of its role in the management of HIV-1 infection, highlighting its key pharmacokinetic and pharmacodynamic properties

    Declaration of Intention for Antonio Franchihtti

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    Declaration of Intention to become a citizen of the United States, as filled out and signed by Antonio Franchitti. Applicant lists himself as a 47 year old farmer residing in Hammonton, New Jersey, born in Campombosso, Italy on 18 April 1870, who sailed on the US bound vessel Britania. Declaration submitted and sworn April 21, 1917

    The role of educative thought in the life and work of Antonio Gramsci

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    Many philosophers have propounded a vision of an improved society, what distinguishes Antonio Gramsci is his continuous effort to make it happen by understanding the process in order to put into practice. Gramsci's conviction about the importance of educative development came from both theory and experience. While there has been considerable examination of Gramsci's work in relation to the Prison Notebooks, this study will seek to address a lacuna in Gramsci scholarship. Using Gramsci's philological method, I analyse Gramsci's pre-prison activity; his pre-prison articles and letters, which, together with his letters from prison, formed part of his educative mission. This educative process was necessary, in order to construct a new party which would develop a collective will, collaboratively, with the masses.In this study therefore, I explore the contexts and formative experiences of the first part of his life together with the intellectual sources from which Gramsci developed his later theories, making central hitherto underemphasised connections between them which informed his writing and ideas. I intend to illustrate that Gramsci's underlying purpose in his writing, and political activity, was not only practical, on how to create a new socialist ruling class, but also educative in forming the mindset and values of his comrades. So that in addition to outlining his vision of a new order, he implicitly guided or explicitly explained the processes by which the necessary changes in social relations and moral climate could be made in order to achieve it. Each person had to engage with the values of the new order so that each could contribute to the construction of a new robust state. It was essential to build a hegemony at the most profound level, one which was dependent on collective understandings and a collective will

    Pharmacogenetics of First-Line Antitubercular Drugs: An Update

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    Background:Tuberculosis (TB) treatment relies on a prolonged first-line antibiotic regimen, including isoniazid, rifampicin (RF), ethambutol (EMB), and pyrazinamide.Pharmacogenetics plays a crucial role in optimizing TB treatment by addressing individual variability in drug metabolism and responses. Genetic polymorphisms can significantly affect pharmacokinetics and therapeutic outcomes. The aim of this review was to explore the role of pharmacogenetics in first-line antibiotics used to treat TB.Methods:We reviewed the literature using PubMed, Scopus, Web of Science, and the Cochrane Library, focusing on articles published in the last 10 years (from December 2014 to December 2024) on the pharmacogenetics of first-line anti-TB drugs. Only English-language studies involving human subjects were included, prioritizing those investigating genetic variants that affect drug bioavailability.Results:In this study, 33 manuscripts were included.N-acetyltransferase 2 Single-nucleotide polymorphisms were associated with different isoniazid acetylation rates, which affect toxicity and efficacy. Genetic variations in CYP2E1, GSTM1, and MnSOD also contribute to hepatotoxicity.For RF, variants in SLCO1B1, ABCB1, PXR, CAR, CES1, and CES2 genes were related to variability in drug absorption, metabolism, and clearance, highlighting the need for personalized dosing strategies. Notably, SLCO1B1 rs4149056 polymorphism is associated with decreased OATP1B1 RF transport activity, potentially leading to increased plasma exposure, whereas other polymorphisms modulate drug exposure and clearance rates. In addition, sex, body weight, and genotype influenced RF pharmacokinetics, suggesting the need for tailored dosing recommendations based on patient characteristics.Similarly, variability in EMB pharmacokinetics is associated with CYP1A2 2159, which is related to a 50% reduction in bioavailability, necessitating dose adjustments in patients coinfected with TB and HIV. Some variants of ABCB1, OATP1B1, PXR, VDR, CYP24A1, and CYP27B1 may further modulate the plasma and intracellular concentrations of EMB, thereby influencing drug efficacy.Conclusions:This review highlights the importance of integrating pharmacogenetic insights into clinical practice to enhance the efficacy of TB treatment, minimize toxicity, and prevent drug resistance. Despite promising evidence, further research and clinical validation are required to implement pharmacogenetics in routine TB management. Future advancements in therapeutic drug monitoring and omics technologies will pave the way for precision medicine in TB therapy

    Sequential therapy with entecavir and pegylated interferon in a cohort of young patients affected by chronic hepatitis B

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    The treatment of patients affected by active chronic hepatitis B (CHB) could performed using a finite-time therapy with pegylated-interferon alpha (PEG-IFN) or indefinite time treatment with nucleos(t)ide analogues (NAs). Current practice guidelines do not provide the combined use of PEG-IFN and NAs, but some studies analyzed various combined approach with NAs and PEG-IFN with encouraging result. In this perspective study we have treated 39 patients with different hepatitis B virus (HBV) genotypes, hepatitis B "e" antigen (HBeAg)-positive/negative using a sequential therapy with entecavir (ETV) 0.5 mg/day monotherapy for 12 weeks followed by combination of ETV and PEG-IFN α-2a 180μg/week for 12 weeks, then PEG-IFN monotherapy for 36 weeks. HBeAg seroconversion rate was 68.2%; HBsAg loss was 33.3%; sustained virological response (SVR) was 64.1%; primary non-response was observed in 8 patients (20.5%) after 12 weeks of PEG-IFN therapy; virological relapse was reported in 6 (15.3%) patients. Viral genotype and hepatitis B surface antigen (HBsAg) decline were the most important predictive factor for PEG-IFN response. The stopping rule after 12 weeks of PEG-IFN therapy is useful for identify the non-responders. Our study offers interesting and promising results using a sequential combined therapy with ETV and PEG-IFN in a cohort of young patient with active CHB. These results, however, should not be generalized and further investigations are required for the confirmation of advantage of this combination approach. This article is protected by copyright. All rights reserved

    Edna Ferber in St. Anthony Hotel, San Antonio, Tex., 1948

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    ''Ferber's novel, Giant, set on a fictitious south Texas ranch, was published in 1952.''''Edna Ferber was in San Antonio on Saturday for a search of the surrounding ranch country for material and characters for a new book. The author of Show boat was registered at the St. Anthony Hotel.'

    Desenganos mysticos para as almas detidas ou enganadas no caminho da perfeiçao... : seu author na lingua hespanhola... Fr. Antonio Arbiol...

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    Sign.: [parágrafo]-2[parágrafo]8, 3[parágrafo]2, A-Z8, 2A-2X8, 2Z1. -- Texto a dos col. -- Port. con viñeta tip. -- Falto de p. 305-350.Sainz Rodrígue
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