subject:(Nucleoside Reverse Transcriptase Inhibitors)

University of KwaZulu-Natal

1. Nagiah, Savania. A biochemical assessment of stress response following acute and prolonged exposure to antiretroviral drugs (nucleoside reverse transcriptase inhibitors) in vitro.

Degree: 2015, University of KwaZulu-Natal

URL: http://hdl.handle.net/10413/14645

► Nucleoside reverse transcriptase inhibitors (NRTIs) are the most extensively used antiretroviral (ARV) drugs in highly active antiretroviral therapy (HAART). The long term use of HAART… (more)

▼ Nucleoside reverse transcriptase inhibitors (NRTIs) are the most extensively used antiretroviral (ARV) drugs in highly active antiretroviral therapy (HAART). The long term use of HAART is associated with changes to metabolic parameters leading to lipodystrophy and metabolic syndrome, as well as toxicity to high energy demand organs e.g. liver, kidney, heart, and nervous system. Underlying the myriad of NRTI-associated adverse health outcomes is mitochondrial (mt) toxicity. Although inhibition of mtDNA synthesis was one of the first identified mechanisms of toxicity, it did not provide a holistic explanation for all NRTIs. Furthermore, variations in adaptive stress responses were observed following acute and chronic exposure to NRTIs. Insight gained from the molecular changes induced by NRTIs will enable effective management and limit adverse health outcomes. The human hepatoma (HepG2) cell line was used as an in vitro model to investigate changes to mt function, cellular redox status, and antioxidant response following acute [24 hour (h)] and prolonged (120 h) exposure to NRTIs – Zidovudine (AZT, 7.1μM); Stavudine (d4T, 4μM); Tenofovir (TFV, 1.2μM). Long term exposure to AZT and d4T reduced mtDNA levels (120h, AZT: 76.1%; d4T:36.1%, p<0.05) and mt function was compromised as evidenced by reduced ATP levels (AZT: 38%; d4T: 56.4%) and increased mt membrane depolarisation (p<0.02). Tenofovir compromised mt function at 120 h independently of depleting mtDNA levels. Oxidative stress parameters were significantly elevated by AZT and TFV at 24h; and all NRTIs at 120 h (p<0.05). Endogenous antioxidant response was highest in TFV in both time periods (120h; p<0.05). Once NRTI induced oxidative stress in HepG2 cells was established, protein homeostatic response to oxidative stress was investigated. Lon protease expression and related endoplasmic reticulum (ER) stress was evaluated. The data showed that ATP-dependent protein homeostasis responses Lon, heat shock protein 60 (HSP60) and ER stress were significantly increased at 24 h (>2 fold); but significantly decreased at 120 h for all NRTIs (p<0.005). The compromised ATP-dependent stress response then led to the assessment of an ATP- dependent drug transporter responsible for efflux of xenobiotics in hepatocytes. The transporter, ATP-binding cassette C4 (ABCC4), is regulated by microRNA (miR-) 124a. Regulation of ABCC4 by miR-124a has implications for bio-accumulation and resultant toxicity. An inverse relationship between miR-124a and ABCC4 mRNA levels in all treatments at both time periods was observed. All NRTIs elevated miR-124a levels at 24 h (p=0.0009) and this observation was consistent in d4T and TFV treated HepG2 cells at 120 h (p<0.0001). This was accompanied with a concomitant decline in ABCC4 mRNA levels (p<0.0001) relative to the control. Prolonged exposure to AZT caused a decrease in miR-124a and elevated ABCC4 mRNA levels. Protein expression of multi-drug resistance protein 4 (MRP4), coded for by ABCC4, did not correlate to mRNA expression. At 120 h, all… Advisors/Committee Members: Chuturgoon, Anil A. (advisor), Phulukdaree, Alisa. (advisor).

Subjects/Keywords: Medical biochemistry.; Nucleoside reverse transcriptase inhibitors.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Nagiah, S. (2015). A biochemical assessment of stress response following acute and prolonged exposure to antiretroviral drugs (nucleoside reverse transcriptase inhibitors) in vitro. (Thesis). University of KwaZulu-Natal. Retrieved from http://hdl.handle.net/10413/14645

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Nagiah, Savania. “A biochemical assessment of stress response following acute and prolonged exposure to antiretroviral drugs (nucleoside reverse transcriptase inhibitors) in vitro.” 2015. Thesis, University of KwaZulu-Natal. Accessed March 08, 2021. http://hdl.handle.net/10413/14645.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Nagiah, Savania. “A biochemical assessment of stress response following acute and prolonged exposure to antiretroviral drugs (nucleoside reverse transcriptase inhibitors) in vitro.” 2015. Web. 08 Mar 2021.

Vancouver:

Nagiah S. A biochemical assessment of stress response following acute and prolonged exposure to antiretroviral drugs (nucleoside reverse transcriptase inhibitors) in vitro. [Internet] [Thesis]. University of KwaZulu-Natal; 2015. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/10413/14645.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Nagiah S. A biochemical assessment of stress response following acute and prolonged exposure to antiretroviral drugs (nucleoside reverse transcriptase inhibitors) in vitro. [Thesis]. University of KwaZulu-Natal; 2015. Available from: http://hdl.handle.net/10413/14645

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Maryland

2. Achuthan, Vasudevan. HIV Reverse Transcriptase Fidelity And Inhibition Are Modulated By Divalent Cations In A Concentration-Dependent Manner In Vitro.

Degree: Cell Biology & Molecular Genetics, 2016, University of Maryland

URL: http://hdl.handle.net/1903/18547

► Human immunodeficiency virus (HIV) rapidly evolves through generation and selection of mutants that can escape drug therapy. This process is fueled, in part, by the… (more)

▼ Human immunodeficiency virus (HIV) rapidly evolves through generation and selection of mutants that can escape drug therapy. This process is fueled, in part, by the presumably highly error prone polymerase reverse transcriptase (RT). Fidelity of polymerases can be influenced by cation co-factors. Physiologically, magnesium (Mg2+) is used as a co-factor by RT to perform catalysis, however, alternative cations including manganese (Mn2+), cobalt (Co2+), and zinc (Zn2+) can also be used. I demonstrate here that fidelity and inhibition of HIV RT can be influenced differently, in vitro, by divalent cations depending on their concentration. The reported mutation frequency for purified HIV RT in vitro is typically in the 10-4 range (per nucleotide addition), making the enzyme several-fold less accurate than most polymerases. Paradoxically, results examining HIV replication in cells indicate an error frequency that is ~10 times lower than the error rate obtained in the test tube. Here, I reconcile, at least in part, these discrepancies by showing that HIV RT fidelity in vitro is in the same range as cellular results, in physiological concentrations of free Mg2+ (~0.25 mM). At low Mg2+, mutation rates were 5-10 times lower compared to high Mg2+ conditions (5-10 mM). Alternative divalent cations also have a concentration-dependent effect on RT fidelity. Presumed promutagenic cations Mn2+ and Co2+ decreases the fidelity of RT only at elevated concentrations, and Zn2+, when present in low concentration, increases the fidelity of HIV-1 RT by ~2.5 fold compared to Mg2+. HIV-1 and HIV-2 RT inhibition by nucleoside (NRTIs) and non-nucleoside RT inhibitors (NNRTIs) in vitro is also affected by the Mg2+ concentration. NRTIs lacking 3'-OH group inhibited both enzymes less efficiently in low Mg2+ than in high Mg2+; whereas inhibition by the “translocation defective RT inhibitor”, which retains the 3ʹ-OH, was unaffected by Mg2+ concentration, suggesting that NRTIs with a 3ʹ-OH group may be more potent than other NRTIs. In contrast, NNRTIs were more effective in low vs. high Mg2+ conditions. Overall, the studies presented reveal strategies for designing novel RT inhibitors and strongly emphasize the need for studying HIV RT and RT inhibitors in physiologically relevant low Mg2+ conditions. Advisors/Committee Members: DeStefano, Jeffrey (advisor).

Subjects/Keywords: Biochemistry; Virology; Molecular biology; Divalent cations; Fidelity; HIV; Non-Nucleoside Reverse Transcriptase Inhibitors; Nucleoside Reverse Transcriptase Inhibitors; Reverse Transcriptase

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APA (6^th Edition):

Achuthan, V. (2016). HIV Reverse Transcriptase Fidelity And Inhibition Are Modulated By Divalent Cations In A Concentration-Dependent Manner In Vitro. (Thesis). University of Maryland. Retrieved from http://hdl.handle.net/1903/18547

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Achuthan, Vasudevan. “HIV Reverse Transcriptase Fidelity And Inhibition Are Modulated By Divalent Cations In A Concentration-Dependent Manner In Vitro.” 2016. Thesis, University of Maryland. Accessed March 08, 2021. http://hdl.handle.net/1903/18547.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Achuthan, Vasudevan. “HIV Reverse Transcriptase Fidelity And Inhibition Are Modulated By Divalent Cations In A Concentration-Dependent Manner In Vitro.” 2016. Web. 08 Mar 2021.

Vancouver:

Achuthan V. HIV Reverse Transcriptase Fidelity And Inhibition Are Modulated By Divalent Cations In A Concentration-Dependent Manner In Vitro. [Internet] [Thesis]. University of Maryland; 2016. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1903/18547.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Achuthan V. HIV Reverse Transcriptase Fidelity And Inhibition Are Modulated By Divalent Cations In A Concentration-Dependent Manner In Vitro. [Thesis]. University of Maryland; 2016. Available from: http://hdl.handle.net/1903/18547

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Kwame Nkrumah University of Science and Technology

3. Sarfo, Fred S.; Zhang, Yuan; Egan, Deirdre; Tetteh, Lambert A.; Phillips, Richard O. Pharmacogenetic associations with plasma efavirenz concentrations and clinical correlates in a retrospective cohort of Ghanaian HIV-infected patients.

Degree: 2013, Kwame Nkrumah University of Science and Technology

URL: http://dspace.knust.edu.gh:8080/jspui/handle/123456789/11869

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Objectives: Efavirenz is widely used in first-line antiretroviral therapy in sub-Saharan Africa. However, exposure to efavirenz shows marked interindividual variability that is genetically mediated with… (more)

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Objectives: Efavirenz is widely used in first-line antiretroviral therapy in sub-Saharan Africa. However, exposure to efavirenz shows marked interindividual variability that is genetically mediated with potential for important pharmacodynamic consequences. The aims of this study were to assess the frequencies of CYP2B6, CYP2A6, UGT2B7 and CAR single nucleotide polymorphisms (SNPs) and their impact on plasma efavirenz concentration and clinical/ immunological responses in Ghanaian patients. Methods: Genomic DNA from 800 HIV-infected patients was genotyped for selected SNPs by real-time PCR-based allelic discrimination. Mid-dose plasma efavirenz concentrations were measured for 521 patients using HPLC with UVdetection. Clinical outcomes in 299 patients on efavirenzwere retrospectively assessed.Univariate andmultivariatelinear regressionwereperformedusingbest subset selection.Time-to-eventoutcomeswereanalysedusingaCox proportional hazards regressionmodel. Results: The variant allele frequencies for CYP2B6 516G.T (rs3745274), CYP2B6 983T.C (rs28399499), CYP2A6 248T.G (CYP2B6*9B; rs28399433), UGT2B7 802C.T (UGT2B7*2; rs7439366), UGT2B7 735A.G (UGT2B7*1c; rs28365062) and CAR 540C.T (rs2307424) were 48%, 4%, 3%, 23%, 15% and 7%, respectively. CYP2B6 516G.T, CYP2B6 983T.C and CYP2A6 248T.G were associated with significantly elevated efavirenz concentrations. A trend towards association between plasma efavirenz concentration and CAR 540C.T was observed. CYP2B6 516G homozygosity was associated with immunological failure [adjusted hazards ratio compared with T homozygosity, 1.70 (1.04–2.76); P¼0.03]. Conclusions:CYP2B6andCYP2A6SNPswereassociatedwithhigher plasmaefavirenzconcentrationsduetoreduction inmajor and minor phase I routes of elimination, respectively. Further prospective studies are needed to validate the pharmacodynamic correlates of these polymorphisms in this population.

An article published by Oxford University Press an is available at doi:10.1093/jac/dkt372

KNUST

Subjects/Keywords: non-nucleoside reverse transcriptase inhibitors; Africa; pharmacokinetics; pharmacodynamics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sarfo, Fred S.; Zhang, Yuan; Egan, Deirdre; Tetteh, Lambert A.; Phillips, R. O. (2013). Pharmacogenetic associations with plasma efavirenz concentrations and clinical correlates in a retrospective cohort of Ghanaian HIV-infected patients. (Thesis). Kwame Nkrumah University of Science and Technology. Retrieved from http://dspace.knust.edu.gh:8080/jspui/handle/123456789/11869

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Sarfo, Fred S.; Zhang, Yuan; Egan, Deirdre; Tetteh, Lambert A.; Phillips, Richard O. “Pharmacogenetic associations with plasma efavirenz concentrations and clinical correlates in a retrospective cohort of Ghanaian HIV-infected patients.” 2013. Thesis, Kwame Nkrumah University of Science and Technology. Accessed March 08, 2021. http://dspace.knust.edu.gh:8080/jspui/handle/123456789/11869.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Sarfo, Fred S.; Zhang, Yuan; Egan, Deirdre; Tetteh, Lambert A.; Phillips, Richard O. “Pharmacogenetic associations with plasma efavirenz concentrations and clinical correlates in a retrospective cohort of Ghanaian HIV-infected patients.” 2013. Web. 08 Mar 2021.

Vancouver:

Sarfo, Fred S.; Zhang, Yuan; Egan, Deirdre; Tetteh, Lambert A.; Phillips RO. Pharmacogenetic associations with plasma efavirenz concentrations and clinical correlates in a retrospective cohort of Ghanaian HIV-infected patients. [Internet] [Thesis]. Kwame Nkrumah University of Science and Technology; 2013. [cited 2021 Mar 08]. Available from: http://dspace.knust.edu.gh:8080/jspui/handle/123456789/11869.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sarfo, Fred S.; Zhang, Yuan; Egan, Deirdre; Tetteh, Lambert A.; Phillips RO. Pharmacogenetic associations with plasma efavirenz concentrations and clinical correlates in a retrospective cohort of Ghanaian HIV-infected patients. [Thesis]. Kwame Nkrumah University of Science and Technology; 2013. Available from: http://dspace.knust.edu.gh:8080/jspui/handle/123456789/11869

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Kentucky

4. Fowler, Benjamin J. NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS ARE ANTI-INFLAMMATORY AND TARGET DRY AGE-RELATED MACULAR DEGENERATION.

Degree: 2014, University of Kentucky

URL: https://uknowledge.uky.edu/physiology_etds/17

► Age-related macular degeneration (AMD) is a principal cause of blindness in the United States and other industrialized nations. An estimated 10 million Americans are afflicted… (more)

Subjects/Keywords: Nucleoside reverse transcriptase inhibitors; age-related macular degeneration; NLRP3 inflammasome; P2X7; Alu RNA; Ophthalmology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Fowler, B. J. (2014). NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS ARE ANTI-INFLAMMATORY AND TARGET DRY AGE-RELATED MACULAR DEGENERATION. (Doctoral Dissertation). University of Kentucky. Retrieved from https://uknowledge.uky.edu/physiology_etds/17

Chicago Manual of Style (16^th Edition):

Fowler, Benjamin J. “NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS ARE ANTI-INFLAMMATORY AND TARGET DRY AGE-RELATED MACULAR DEGENERATION.” 2014. Doctoral Dissertation, University of Kentucky. Accessed March 08, 2021. https://uknowledge.uky.edu/physiology_etds/17.

MLA Handbook (7^th Edition):

Fowler, Benjamin J. “NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS ARE ANTI-INFLAMMATORY AND TARGET DRY AGE-RELATED MACULAR DEGENERATION.” 2014. Web. 08 Mar 2021.

Vancouver:

Fowler BJ. NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS ARE ANTI-INFLAMMATORY AND TARGET DRY AGE-RELATED MACULAR DEGENERATION. [Internet] [Doctoral dissertation]. University of Kentucky; 2014. [cited 2021 Mar 08]. Available from: https://uknowledge.uky.edu/physiology_etds/17.

Council of Science Editors:

Fowler BJ. NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS ARE ANTI-INFLAMMATORY AND TARGET DRY AGE-RELATED MACULAR DEGENERATION. [Doctoral Dissertation]. University of Kentucky; 2014. Available from: https://uknowledge.uky.edu/physiology_etds/17

University of Georgia

5. Blue, Shawn Kendale. Pharmacokinetics of anti-HIV agents in rodents.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/26575

► The treatment of HIV/AIDS is one of, if not, the most challenging medical enigmas of the 20th and 21st centuries. At the time of its… (more)

▼ The treatment of HIV/AIDS is one of, if not, the most challenging medical enigmas of the 20th and 21st centuries. At the time of its discovery, HIV patients were predominantly homosexual White males in America. The demographics have changed drastically over the past two decades. Now women make up nearly 50% of global HIV/AIDS patients. The current feminization of HIV demographics has led to another obstacle, mother to child transmission (MTCT). These statistics, coupled with the fact that vertical transmission is the largest factor in the number of newly diagnosed juvenile HIV/AIDS patients, create a need to optimize treatment of HIV positive pregnant women, to reduce vertical transmission of HIV. It has been shown that administration of anti-HIV medications during pregnancy, delivery and to the infant after birth greatly reduces the risk of vertical transmission. Understanding the pharmacokinetics of HIV/AIDS medications alone and in combination during pregnancy is necessary in the development of more effective methods of vertical transmission prophylaxis. Using a pregnant rat model, we have developed analytical methods and investigated the pharmacokinetics and placental transport of anti-HIV drugs alone and in combination. These studies allowed us to determine and understand any possible interactions between drugs in combination. Studies were performed on timed-pregnant Sprague-Dawley rats and pharmacokinetic analysis was performed using WinNonlin. While current methods of treating HIV/AIDS patients have been highly successful, the chance of viral mutations and resistance to Anti-Retroviral Therapy often occurs. In order to combat the resistance of reverse transcriptase inhibitors (NRTI and NNRTI) and protease inhibitors, scientists have continually searched for additional targets on HIV. For instance, integrase inhibitors, block the action of integrase, a viral enzyme, which integrates HIV DNA into the target cells. We have determined the pharmacokinetic profile of an investigational integrase inhibitor. In vivo animal studies were being performed on male Sprague-Dawley rats and female PXR-KO and hPXR transgenic mice and pharmacokinetic analysis was performed using WinNonlin.

Subjects/Keywords: HIV; Pharmacokinetics; Stavudine; Lamivudine; D4T; DDC; Placental Transport; NRTI; Nucleoside Reverse Transcriptase Inhibitors; HPLC; Antiviral Drugs; Integrase Inhibitors

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Blue, S. K. (2014). Pharmacokinetics of anti-HIV agents in rodents. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/26575

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Blue, Shawn Kendale. “Pharmacokinetics of anti-HIV agents in rodents.” 2014. Thesis, University of Georgia. Accessed March 08, 2021. http://hdl.handle.net/10724/26575.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Blue, Shawn Kendale. “Pharmacokinetics of anti-HIV agents in rodents.” 2014. Web. 08 Mar 2021.

Vancouver:

Blue SK. Pharmacokinetics of anti-HIV agents in rodents. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/10724/26575.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Blue SK. Pharmacokinetics of anti-HIV agents in rodents. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/26575

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Georgia

6. Li, Ting. Physiologically-based pharmacokinetic modeling approach for drug disposition in human and pregnant rat.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/24207

► Physiologically-based pharmacokinetic (PBPK) modeling is a useful approach to investigate the absorption, distribution, metabolism and elimination (ADME) of a compound in animals as well as… (more)

▼ Physiologically-based pharmacokinetic (PBPK) modeling is a useful approach to investigate the absorption, distribution, metabolism and elimination (ADME) of a compound in animals as well as humans. In this dissertation, a PBPK model was constructed to describe dose and time dependent pharmacokinetics of dichloroacetic acid (DCA) in humans. DCA is used clinically to treat metabolic acidosis and is also a potential carcinogenic contaminate in drinking water. DCA inactivates its own metabolic enzyme, glutathione transferase zeta (GSTzeta) which leads to an increased half-life after repeated dosing. GSTzeta is also a major enzyme in tyrosine catabolism and deficiency in this metabolic pathway resulting in the accumulation of intermediate metabolites is proposed as the mechanism behind DCA carcinogenicity. Therefore, quantitative evaluation of DCA pharmacokinetics and compromised GSTzeta activity following repeated dosing is critical in understanding the pharmacological and toxicological effects arising from human exposure. Nucleoside reverse transcriptase inhibitors (NRTIs) are the primary antiretroviral drugs used in highly active antiretroviral therapy (HAART), which is successful in reducing mother-to-child transmission (MTCT) of HIV. However, limited in vivo pharmacokinetic data are available for NRTI disposition in pregnant women as well as their fetuses. PBPK models are advantageous in that assessment of special physiological situations, such as pregnancy and the compounds pharmacokinetics behavior, in animal, tissues that otherwise can never been assessed in human, such as placenta and fetus. The first PBPK models describing perinatal exposure to NRTIs and the potential drug-drug interactions are reported in this dissertation. Based on the model simulations, NRTIs cross placenta through active transport, not only passive diffusion. Consequently, when co-administered, NRTI clearance from maternal tissues may be altered. Drug-drug interactions on transplacental transfer suggest a complex mechanism including up-regulated/down-regulated transport, which may be the result of multiple NRTIs transporters located on both the maternal and fetal side of the placenta. Because of the similarity between human and rat placenta, including similar transporter compositions, the interactions identified in present study may have clinical significance and thus, require careful monitoring during administration to pregnant women to protect against mother-to-child transmission (MTCT) of HIV.

Subjects/Keywords: physiologically-based pharmacokinetic model; dichloroacetic acid; nucleoside reverse transcriptase inhibitors; pregnancy; drug-drug interaction; suicide inhibition

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Li, T. (2014). Physiologically-based pharmacokinetic modeling approach for drug disposition in human and pregnant rat. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/24207

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Li, Ting. “Physiologically-based pharmacokinetic modeling approach for drug disposition in human and pregnant rat.” 2014. Thesis, University of Georgia. Accessed March 08, 2021. http://hdl.handle.net/10724/24207.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Li, Ting. “Physiologically-based pharmacokinetic modeling approach for drug disposition in human and pregnant rat.” 2014. Web. 08 Mar 2021.

Vancouver:

Li T. Physiologically-based pharmacokinetic modeling approach for drug disposition in human and pregnant rat. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/10724/24207.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Li T. Physiologically-based pharmacokinetic modeling approach for drug disposition in human and pregnant rat. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/24207

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Georgia

7. alnouti, yazen mohammed. The application of liquid chromatography and mass spectrometry for the determination of nucleoside analogues in biological matrices.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/21743

► Multidrug therapy has become the standard treatment of acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV). Nucleoside reverse transcriptase inhibitors (NRTIs) are… (more)

▼ Multidrug therapy has become the standard treatment of acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV). Nucleoside reverse transcriptase inhibitors (NRTIs) are used in all AIDS combination therapies. In combination therapies, there is a high potential for pharmacokinetic interaction between the individual drugs. This interaction can alter the transport profile of anti HIV agents to the fetus in pregnant women. In order to study pharmacokinetic interactions, sensitive and valid analytical methods are required for the quantification of NRTIs in different biological matrices. This dissertation focuses on developing valid analytical methods to quantify NRTIs in different pregnant rat matrices. Lamivudine (3TC) and zidovudine (AZT) were studied as model NRTIs. These matrices include plasma, amniotic fluid, placenta and fetus. Method development includes 3 steps, sample preparation, chromatographic separation and spectroscopic detection. Due to the complicity of tissue matrices, ultra clean sample extraction is required. Different sample preparation techniques like protein precipitation by acids, organic solvents and salting out, solid phase extraction (SPE) and liquid-liquid extraction (LLE) were used. High performance liquid chromatography (HPLC) and capillary electrophoresis (CE) are the separation techniques that were used. For spectrometric detection, ultraviolet (UV) and mass spectrometry (MS) detectors were used. After developing the optimum sample extraction, chromatographic separation and spectrometric detection conditions, the methods were validated according to FDA criteria. The validated methods were successfully applied in animal studies using the pregnant rat model. The animal studies have shown that fetal exposure to 3TC was significantly increased when co-administered with AZT. The mechanism of this drug-drug interaction has not been found, but it may be due to AZT competitive inhibition of the 3TC efflux transporters in the fetal-facing side of the placenta. These results suggest that the underlying mechanism behind the 3TC placental transport in rats is carrier mediated.

Subjects/Keywords: HPLC; CE; MS; SPE; LLE; Sample Preparation; liquid chromatography; Biological matrices; Nucleoside reverse transcriptase inhibitors; Lamivudine; 3TC; Zidovudine; AZT; placental transport

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

alnouti, y. m. (2014). The application of liquid chromatography and mass spectrometry for the determination of nucleoside analogues in biological matrices. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/21743

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

alnouti, yazen mohammed. “The application of liquid chromatography and mass spectrometry for the determination of nucleoside analogues in biological matrices.” 2014. Thesis, University of Georgia. Accessed March 08, 2021. http://hdl.handle.net/10724/21743.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

alnouti, yazen mohammed. “The application of liquid chromatography and mass spectrometry for the determination of nucleoside analogues in biological matrices.” 2014. Web. 08 Mar 2021.

Vancouver:

alnouti ym. The application of liquid chromatography and mass spectrometry for the determination of nucleoside analogues in biological matrices. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/10724/21743.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

alnouti ym. The application of liquid chromatography and mass spectrometry for the determination of nucleoside analogues in biological matrices. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/21743

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Bath

8. Mafuva, Christopher. Effect of ethinylestradiol and levonorgestrel on nucleoside reverse transcriptase inhibitor-induced apoptosis in human cervical epithelial cancer cells.

Degree: Thesis (D.Health), 2019, University of Bath

URL: https://researchportal.bath.ac.uk/en/studentthesis/effect-of-ethinylestradiol-and-levonorgestrel-on-nucleoside-reverse-transcriptase-inhibitorinduced-apoptosis-in-human-cervical-epithelial-cancer-cells(9d6b72a6-62d5-4608-bb3e-a0d2b6685f8d).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.817805

► Preliminary findings suggest an increase in cervical cancer among sub-Sahara African women on highly active antiretroviral treatment (HAART). There has been a sharp rise in… (more)

▼ Preliminary findings suggest an increase in cervical cancer among sub-Sahara African women on highly active antiretroviral treatment (HAART). There has been a sharp rise in serious non-AIDS events among HAART recipients. This study explored the effect of co-administering combined contraceptive hormones with antiretroviral drugs on promoting human cervical epithelial cancer cell proliferation, DNA mutation and cell transformation. Combinations of abacavir (ABC), zidovudine (ZDV), lamivudine (3TC), stavudine (d4T) and nevirapine (NVP) were co-administered with either ethinylestradiol or levonorgestrel. The combinations ZDV+3TC, ABC+ZDV+3TC, ZDV+3TC+NVP and d4T+3TC+NVP induced a time-dependent antiproliferative effect on HeLa cells. Co-treatment with levonorgestrel demonstrated antiproliferative effects on combination antiretroviral drug-treated cells while co-administering 0.5μg/ml ethinylestradiol increases HeLa cell proliferation (P≤ 0.5). Single drugs (ABC, ZDV, 3TC, d4T and NVP) showed a time-dependent DNA double strand breakage in both HeLa and Chinese hamster ovary cells. Both levonorgestrel and ethinylestradiol drastically increased apoptosis in ABC+3TC-, ZDV+3TC-, ABC+ZDV+3TC- and d4T+3TC+NVP-treated cells. Highly active antiretroviral treatment transformed pre-monocyte lymphoma (U937) cells to adherent cells with macrophage-like morphology and increased superoxide production. Increased HeLa cell death by apoptosis following co-administration of triple combination antiretroviral drugs with levonorgestrel suggests a protective effect against human cervical cancer cell proliferation among HAART users. Despite the drastic induction of apoptosis by 0.5μg/ml ethinylestradiol, ABC+3T-, ZDV+3TC-, ABC+ZDV+3TC- and ZDV+3TC+NVP-treated cells did not significantly differ from the untreated cells in their proliferation assayed by MTT (P≤0.05), thus suggesting a proliferative effect on the human cervical epithelial cancer cells. Transformation to macrophage-like morphology and increased superoxide anion production in U937 cells suggest precipitation of serious non-AIDs events among HAART users. The antiproliferative effect of HAART on cervical cancer cells suggests a protective role against cell proliferation. The antiproliferative effect of levonorgestrel suggests its potential as a progestogen-only contraceptive alternative for women on HAART treatment. The present results also suggest the downside effect of HAART through precipitation of serious non-AIDS events. Further in vivo clinical studies maybe of interest.

Subjects/Keywords: Nucleoside; reverse transcriptase inhibitor; apoptosis; cervical; cancer cells

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mafuva, C. (2019). Effect of ethinylestradiol and levonorgestrel on nucleoside reverse transcriptase inhibitor-induced apoptosis in human cervical epithelial cancer cells. (Doctoral Dissertation). University of Bath. Retrieved from https://researchportal.bath.ac.uk/en/studentthesis/effect-of-ethinylestradiol-and-levonorgestrel-on-nucleoside-reverse-transcriptase-inhibitorinduced-apoptosis-in-human-cervical-epithelial-cancer-cells(9d6b72a6-62d5-4608-bb3e-a0d2b6685f8d).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.817805

Chicago Manual of Style (16^th Edition):

Mafuva, Christopher. “Effect of ethinylestradiol and levonorgestrel on nucleoside reverse transcriptase inhibitor-induced apoptosis in human cervical epithelial cancer cells.” 2019. Doctoral Dissertation, University of Bath. Accessed March 08, 2021. https://researchportal.bath.ac.uk/en/studentthesis/effect-of-ethinylestradiol-and-levonorgestrel-on-nucleoside-reverse-transcriptase-inhibitorinduced-apoptosis-in-human-cervical-epithelial-cancer-cells(9d6b72a6-62d5-4608-bb3e-a0d2b6685f8d).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.817805.

MLA Handbook (7^th Edition):

Mafuva, Christopher. “Effect of ethinylestradiol and levonorgestrel on nucleoside reverse transcriptase inhibitor-induced apoptosis in human cervical epithelial cancer cells.” 2019. Web. 08 Mar 2021.

Vancouver:

Mafuva C. Effect of ethinylestradiol and levonorgestrel on nucleoside reverse transcriptase inhibitor-induced apoptosis in human cervical epithelial cancer cells. [Internet] [Doctoral dissertation]. University of Bath; 2019. [cited 2021 Mar 08]. Available from: https://researchportal.bath.ac.uk/en/studentthesis/effect-of-ethinylestradiol-and-levonorgestrel-on-nucleoside-reverse-transcriptase-inhibitorinduced-apoptosis-in-human-cervical-epithelial-cancer-cells(9d6b72a6-62d5-4608-bb3e-a0d2b6685f8d).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.817805.

Council of Science Editors:

Mafuva C. Effect of ethinylestradiol and levonorgestrel on nucleoside reverse transcriptase inhibitor-induced apoptosis in human cervical epithelial cancer cells. [Doctoral Dissertation]. University of Bath; 2019. Available from: https://researchportal.bath.ac.uk/en/studentthesis/effect-of-ethinylestradiol-and-levonorgestrel-on-nucleoside-reverse-transcriptase-inhibitorinduced-apoptosis-in-human-cervical-epithelial-cancer-cells(9d6b72a6-62d5-4608-bb3e-a0d2b6685f8d).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.817805

University of KwaZulu-Natal

9. Poonan, Preantha. Putative HIV-1 reverse transcriptase inhibitors: design, synthesis, in vitro evaluation and in silico analysis.

Degree: 2018, University of KwaZulu-Natal

URL: https://researchspace.ukzn.ac.za/handle/10413/18462

► One of the most significant treatments for HIV-1 infection has been the combination of drugs targeting the HIV life cycle with the aim of preventing… (more)

▼ One of the most significant treatments for HIV-1 infection has been the combination of drugs targeting the HIV life cycle with the aim of preventing further destruction of the host immune system. This study addresses the design, synthesis, in vitro evaluation, and in silico analysis of putative HIV-1 reverse transcriptase (RT) inhibitors. The inhibitors comprise two structurally diverse components which are intended to bind separately to the enzyme allosteric site and to a location at, or close to, the polymerase active site. Therefore, the hydrophobic N-tritylated phalo-DL-phenylalanine derivatives (fluoro, chloro, bromo, iodo) have been coupled to 8-(6- aminohexyl) amino-adenosine-3',5'-cyclic monophosphate through N-hydroxysuccinimidecarbodiimide chemistry. Compounds were characterized by thin layer chromatography, UV spectroscopy, MALDI-TOF mass spectrometry and proton NMR spectrometry. A reverse transcriptase colorimetric assay kit, which features a sandwich ELISA protocol, based on biotin-avidin and digoxygenin-anti DIG interactions, was used for quantitative determination of the inhibitory effect of synthesized compounds on recombinant HIV-1 reverse transcriptase activity in vitro. Molecular docking simulations of the chimeric inhibitors within the allosteric site of HIV-1 RT, were performed using AutoDock Vina. The predicted binding associations were compared with laboratory findings on HIV-1 RT inhibition. Two dimensional representations of protein-ligand interactions were generated using LigPlot. The non-halogenated N-trityl-L-phenylalanine-8-(6-aminohexyl)amino-adenosine-3',5'-cyclic monophosphate derivative (4a) inhibited RT activity down to 57 % at 10-4 M, while the Ntrityl-para-fluoro-DL-phenylalanine-8-(6-aminohexyl)aminoadenosine-3′,5′-cyclic monophosphate derivative (4b) was the strongest RT inhibitor reducing RT activity to 69 % at 10-7 M (IC50 = 29.2 μM). In the same assay, Nevirapine, a first-line anti-retroviral drug, showed a decline in RT activity down to 43% at 10-5 M (IC50 = 3.03 μM). Ranking of inhibitors according to estimated docking energies obtained from in silico docking was in excellent agreement with potencies calculated from experimental studies. The docking score of N-trityl-para-fluoro-DL-phenylalaline-8-(6-aminohexyl)amino-adenosine-3',5'-cyclic monophosphate was -8.8 kcal/mol, while that of Nevirapine was -9.9 kcal/mol. The benzene rings of the N-trityl-fluoro-DL-phenylalanine-8-(6-aminohexyl) amino-adenosine-3',5'-cyclic monophosphate derivative formed hydrophobic interactions with hydrophobic, non-aromatic amino acid residues Pro176 and Val179 in the allosteric site. Nevirapine, on the other hand showed strong van der Waals interactions with Val106 ,Val179 and Tyr188 due to the aromatic properties of the pyridine ring. Possible π-π stacking between phenyl rings of Nevirapine and Tyr 181/Tyr188 aromatic side chains may also be present. Other HIV-1 RT large subunit residues in the allosteric site common to the binding of Nevirapine and the active… Advisors/Committee Members: Gupthar, Abindra Supersad. (advisor).

Subjects/Keywords: Reverse transcriptase inhibitors.; Silico analysis.; In vitro evaluation.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Poonan, P. (2018). Putative HIV-1 reverse transcriptase inhibitors: design, synthesis, in vitro evaluation and in silico analysis. (Thesis). University of KwaZulu-Natal. Retrieved from https://researchspace.ukzn.ac.za/handle/10413/18462

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Poonan, Preantha. “Putative HIV-1 reverse transcriptase inhibitors: design, synthesis, in vitro evaluation and in silico analysis.” 2018. Thesis, University of KwaZulu-Natal. Accessed March 08, 2021. https://researchspace.ukzn.ac.za/handle/10413/18462.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Poonan, Preantha. “Putative HIV-1 reverse transcriptase inhibitors: design, synthesis, in vitro evaluation and in silico analysis.” 2018. Web. 08 Mar 2021.

Vancouver:

Poonan P. Putative HIV-1 reverse transcriptase inhibitors: design, synthesis, in vitro evaluation and in silico analysis. [Internet] [Thesis]. University of KwaZulu-Natal; 2018. [cited 2021 Mar 08]. Available from: https://researchspace.ukzn.ac.za/handle/10413/18462.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Poonan P. Putative HIV-1 reverse transcriptase inhibitors: design, synthesis, in vitro evaluation and in silico analysis. [Thesis]. University of KwaZulu-Natal; 2018. Available from: https://researchspace.ukzn.ac.za/handle/10413/18462

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Hong Kong

10. 张{275b70}. Effect of non-nucleoside reverse transcriptase inhibitors on inflammatory responses in endothelial cells.

Degree: 2015, University of Hong Kong

URL: http://hdl.handle.net/10722/221518

► Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are one of the first-line treatments for patients with human immunodeficiency virus (HIV). However, epidemiological studies suggest an increased prevalence… (more)

▼ Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are one of the first-line treatments for patients with human immunodeficiency virus (HIV). However, epidemiological studies suggest an increased prevalence of cardiovascular diseases (CVD) in NNRTIs-treated HIV-infected patients. Since inflammation is a risk factor of CVD, the present study aimed to determine whether or not NNRTIs, efavirenz (EFV) and nevirapine (NPV), stimulate vascular inflammation. Human umbilical vein endothelial cells (HUVECs) were incubated with EFV (5 or 25 μM), NPV (5 or 25 μM) or their vehicle (dimethyl sulfoxide, 0.1%) for 2 or 24 hours in the absence (the control conditon), or presence of hydrogen peroxide [H2O2 (50 μM), to mimic oxidative stress] or lipopolysaccharides [LPS (10 μg/ml), to mimic bacterial infection]. The releases of inflammatory mediators by HUVECs, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8) and C-reactive proteins (CRP), were determined by measuring their levels in the medium with ELISA. The mRNA levels of TNF-α, IL-6 and IL-8, and the protein presence of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-1 and -2 in HUVECs were measured with real time-polymerase chain reaction assay and Western immunoblotting, respectively. After incubation with EFV (25 μM) for 2 or 24 hours, the number of viable cells, measured by the colorimetric assay with MTT, was significantly reduced. HUVECs treated with this concentration of EFV for 24 hours also showed reduced protein expression of eNOS. Despite these seemingly impairment of endothelial function, the release of CRP and TNF-α, mRNA level of IL-6 and IL-8, and the protein expressions of iNOS and COX-2, in the absence or presence of H2O2 or LPS, were not affected by EFV. As such, it is unlikely that EFV can induce significant inflammatory responses in endothelial cells. In view of the plasma level of EFV after an oral intake (12.89 μM) was lower than the high concentration (25 μM) used in the study, it is unlikely that the clinical use of EFV would cause endothelial cell death. By contrast, NPV, at both concentrations tested, did not affect the protein expressions of iNOS, COX-1 and COX-2, and the mRNA level of TNF-α, IL-6 and IL-8 in HUVECs, but after 24 hours reduced CRP release in the presence of H2O2 (at high concentration) and IL-6 release in the presence of LPS (at low concentration). These findings suggest that NPV unlikely causes endothelial inflammation. NPV also did not affect the number of viable cells, thus indicating that it does not have cytotoxic effects on endothelial cells. Nevertheless, NPV down-regulated eNOS in the presence of H2O2 after 24 hours; this effect was observed at both concentrations tested, which are within the plasma concentrations in human, thus suggesting that it may have the potential to impair endothelial function during oxidative stress. In summary, the present findings suggest that NNRTIs would not cause significant endothelial…

Subjects/Keywords: Inflammation; Endothelial cells; Reverse transcriptase - Inhibitors

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

张{275b70}. (2015). Effect of non-nucleoside reverse transcriptase inhibitors on inflammatory responses in endothelial cells. (Thesis). University of Hong Kong. Retrieved from http://hdl.handle.net/10722/221518

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

张{275b70}. “Effect of non-nucleoside reverse transcriptase inhibitors on inflammatory responses in endothelial cells.” 2015. Thesis, University of Hong Kong. Accessed March 08, 2021. http://hdl.handle.net/10722/221518.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

张{275b70}. “Effect of non-nucleoside reverse transcriptase inhibitors on inflammatory responses in endothelial cells.” 2015. Web. 08 Mar 2021.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Vancouver:

张{275b70}. Effect of non-nucleoside reverse transcriptase inhibitors on inflammatory responses in endothelial cells. [Internet] [Thesis]. University of Hong Kong; 2015. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/10722/221518.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

张{275b70}. Effect of non-nucleoside reverse transcriptase inhibitors on inflammatory responses in endothelial cells. [Thesis]. University of Hong Kong; 2015. Available from: http://hdl.handle.net/10722/221518

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

Université Montpellier II

11. Moustapha Abba Moussa, Daouda. Développement d'inhibiteurs de la dimérisation du complexe de la Reverse Transcription du VIH-1 : Dimerization of HIV-1 Reverse Transcriptase as a potent target to block HIV replication.

Degree: Docteur es, Biologie Santé, 2013, Université Montpellier II

URL: http://www.theses.fr/2013MON20238

►

Le virus de l'immunodéficience humain de type 1 VIH-1 est un rétrovirus responsable d'une pandémie touchant actuellement 34 millions de personnes dont près de 25… (more)

▼

Le virus de l'immunodéficience humain de type 1 VIH-1 est un rétrovirus responsable d'une pandémie touchant actuellement 34 millions de personnes dont près de 25 millons en sont morts. En dépit des grands progrès réalisés dans le développement de nouveaux médicaments visant à bloquer la réplication de ce virus, l'émergence rapide de souches virales mutantes résistantes imposent l'urgence et la nécessité de développer de nouvelles stratégies thérapeutiques pour combattre ce virus. La Reverse Transcriptase (RT) duVIH-1 joue un rôle majeur dans le cycle viral puisqu'elle est responsable de convertir l'ARN génomique simple brin en ADN double afin d'intégrer l'ADN génomique de la cellule hôte. La forme biologique de la RT est un hétérodimère formé de la sous unité p66 et la sous unité p51. Les sous unités sont constituées des sous domaines fingers, palm, « connection », thumb et RNase H, ce dernier étant absent sur la sous unité p51. L'activation de la RT est un processus en deux étapes : la première étape consiste en l'association rapide des deux sous unités, suivie d'une deuxième étape plus lente, correspondant à des changements conformationnels fins à l'interface entre p66/p51.Dans l'objectif d'inhiber la fonction de la RT, nous avons proposé une nouvelle stratégie fondée sur l'utilisation des peptides interfacials courts dérivant de séquences hautement conserver de la RT, capables de cibler efficacement les interactions protéine/protéine et de bloquer la dimérisation et l'activation par maturation de la RT. La dimérisation des deux sous unités implique leur interaction part les domaines de connexion. Dans la première partie de ce travail de thèse, nous avons criblé et isolé des peptides capables d'interférer avec cette interaction impliquant un « cluster » de résidus aromatiques. Nous avons identifié un peptide court PID4, et démontré que ce peptide induit un changement de conformation de la RT, entrainant la dissociation du complexe. La maturation implique l'interaction de résidus localisés au niveau de « hot spot » dans le domaine RNase H de p66 et thumb de p51. Dans la deuxième partie de cette thèse, nous avons sélectionné un peptide court, P27, issus du domaine thumb pouvant inhiber l'étape de la « maturation » (P27). Ces deux classes de peptides bloquent la réplication virale et sont efficaces sur plusieurs souches virales et sur des mutants résistants aux NNRTIS et NRTIS.Les résultats obtenus sur nos deux classes d'inhibiteurs peptidiques, démontrent bien que la dimérisation et la maturation de la RT constituent des cibles de choix pour bloquer l'activité polymérase de la RT et ainsi stopper la prolifération virale par un nouvel concept moins exposer à l'émergence des mutation de résistance.

The human immunodeficiency virus type 1 (HIV-1) is a retrovirus responsible of a disease currently affecting 34 million people and caused the death of 25 million people from its discovery in the 1980s. Despite the great progresses made in the development of new drugs to block the replication of the virus, the rapid…

Advisors/Committee Members: Divita, Gilles (thesis director).

Subjects/Keywords: Vih-1; Reverse Transcriptase; Integrase; Inhibiteurs peptidiques; Résistance; Dimérisation et maturation du VIH; Hiv-1; Reverse Transcriptase; Integrase; Peptides inhibitors; Resistance; Dimerization and maturation of HIV

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Moustapha Abba Moussa, D. (2013). Développement d'inhibiteurs de la dimérisation du complexe de la Reverse Transcription du VIH-1 : Dimerization of HIV-1 Reverse Transcriptase as a potent target to block HIV replication. (Doctoral Dissertation). Université Montpellier II. Retrieved from http://www.theses.fr/2013MON20238

Chicago Manual of Style (16^th Edition):

Moustapha Abba Moussa, Daouda. “Développement d'inhibiteurs de la dimérisation du complexe de la Reverse Transcription du VIH-1 : Dimerization of HIV-1 Reverse Transcriptase as a potent target to block HIV replication.” 2013. Doctoral Dissertation, Université Montpellier II. Accessed March 08, 2021. http://www.theses.fr/2013MON20238.

MLA Handbook (7^th Edition):

Moustapha Abba Moussa, Daouda. “Développement d'inhibiteurs de la dimérisation du complexe de la Reverse Transcription du VIH-1 : Dimerization of HIV-1 Reverse Transcriptase as a potent target to block HIV replication.” 2013. Web. 08 Mar 2021.

Vancouver:

Moustapha Abba Moussa D. Développement d'inhibiteurs de la dimérisation du complexe de la Reverse Transcription du VIH-1 : Dimerization of HIV-1 Reverse Transcriptase as a potent target to block HIV replication. [Internet] [Doctoral dissertation]. Université Montpellier II; 2013. [cited 2021 Mar 08]. Available from: http://www.theses.fr/2013MON20238.

Council of Science Editors:

Moustapha Abba Moussa D. Développement d'inhibiteurs de la dimérisation du complexe de la Reverse Transcription du VIH-1 : Dimerization of HIV-1 Reverse Transcriptase as a potent target to block HIV replication. [Doctoral Dissertation]. Université Montpellier II; 2013. Available from: http://www.theses.fr/2013MON20238

Rhodes University

12. Olomola, Temitope Oloruntoba. Synthesis and evaluation of novel HIV-1 enzyme inhibitors.

Degree: PhD, Faculty of Science, Chemistry, 2011, Rhodes University

URL: http://hdl.handle.net/10962/d1005034

► This study has involved the design, synthesis and evaluation of novel HIV-1 enzyme inhibitors accessed by synthetic elaboration of Baylis-Hillman adducts. Several series of complex… (more)

▼ This study has involved the design, synthesis and evaluation of novel HIV-1 enzyme inhibitors accessed by synthetic elaboration of Baylis-Hillman adducts. Several series of complex coumarin-AZT and cinnamate ester-AZT conjugates have been prepared, in high yields, by exploiting the click reaction between appropriate Baylis-Hillman derived precursors and azidothymidine (AZT), all of which have been fully characterised using spectroscopic techniques. These conjugates, designed as potential dual-action HIV-1 inhibitors, were tested against the appropriate HIV-1 enzymes, i.e. HIV-1 reverse transcriptase and protease or HIV-1 reverse transcriptase and integrase. A number of the ligands have exhibited % inhibition levels and IC50 values comparable to drugs in clinical use, permitting their identification as lead compounds for the development of novel dual-action inhibitors. In silico docking of selected ligands into the active sites of the respective enzymes has provided useful insight into binding conformations and potential hydrogen-bonding interactions with active-site amino acid residues. A series of furocoumarin carboxamide derivatives have been synthesised in four steps starting from resorcinol and these compounds have also been tested for HIV-1 integrase inhibition activity. The structures of unexpected products isolated from Aza-Baylis-Hillman reactions of N-tosylaldimines have been elucidated by spectroscopic analysis, and confirmed by single crystal X-ray analysis. A mechanism for what appears to be an unprecedented transformation has been proposed. Microwave-assisted SeO₂ oxidation of Baylis-Hillman-derived 3-methylcoumarins has provided convenient and efficient access to coumarin-3-carbaldehydes, and a pilot study has revealed the potential of these coumarin-3-carbaldehydes as scaffolds for the construction of tricyclic compounds. The HCl-catalysed reaction of tert-butyl acrylate derived Baylis-Hillman adducts has been shown to afford 3-(chloromethyl)coumarins and α-(chloromethyl)cinnamic acids, the Zstereochemistry of the latter being established by X-ray crystallography. ¹H NMR-based experimental kinetic and DFT-level theoretical studies have been undertaken to establish the reaction sequence and other mechanistic details. Base-catalysed cyclisation on the other hand, has been shown to afford 2H-chromene rather than coumarin derivatives. Advisors/Committee Members: Kaye, Perry, Klein, Rosalyn.

Subjects/Keywords: HIV infections – Treatment; HIV infections – Chemotherapy; HIV (Viruses); Enzyme inhibitors; AZT (Drug); Reverse transcriptase; Proteolytic enzymes; Ligands; Psoralens; Resorcinol

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Olomola, T. O. (2011). Synthesis and evaluation of novel HIV-1 enzyme inhibitors. (Doctoral Dissertation). Rhodes University. Retrieved from http://hdl.handle.net/10962/d1005034

Chicago Manual of Style (16^th Edition):

Olomola, Temitope Oloruntoba. “Synthesis and evaluation of novel HIV-1 enzyme inhibitors.” 2011. Doctoral Dissertation, Rhodes University. Accessed March 08, 2021. http://hdl.handle.net/10962/d1005034.

MLA Handbook (7^th Edition):

Olomola, Temitope Oloruntoba. “Synthesis and evaluation of novel HIV-1 enzyme inhibitors.” 2011. Web. 08 Mar 2021.

Vancouver:

Olomola TO. Synthesis and evaluation of novel HIV-1 enzyme inhibitors. [Internet] [Doctoral dissertation]. Rhodes University; 2011. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/10962/d1005034.

Council of Science Editors:

Olomola TO. Synthesis and evaluation of novel HIV-1 enzyme inhibitors. [Doctoral Dissertation]. Rhodes University; 2011. Available from: http://hdl.handle.net/10962/d1005034

13. Pribut, Nicole. The design and synthesis of novel HIV-1 non-nucleoside reverse transcriptase inhibitors.

Degree: MSc, Chemistry and Polymer Science, 2015, Stellenbosch University

URL: http://hdl.handle.net/10019.1/96693

► ENGLISH ABSTRACT: Since its discovery in the 1980’s, HIV has affected the lives of millions of individuals around the globe. Despite obvious need and an… (more)

▼ ENGLISH ABSTRACT: Since its discovery in the 1980’s, HIV has affected the lives of millions of individuals around the globe. Despite obvious need and an enormous amount of research a cure has remained elusive due to the rapid onset of mutated forms of the virus. However, there has been considerable success in reducing viral levels of infected individuals through the use of highly active antiretroviral therapy (HAART). The first-line regimen HAART mainly targets reverse transcriptase (RT) through the employment of two nucleoside RT inhibitors (NRTIs) and a nonnucleoside RT inhibitor (NNRTI). NNRTIs target an allosteric pocket situated about 10 Å from the catalytic site and cause a conformational change in the enzyme upon binding, leading to the inhibition of viral replication. There are currently 5 FDA approved NNRTIs on the market which successfully inhibit viral replication, but the use of these drugs is becoming limited due to the onset of drug resistant strains of the virus. In light of this need for the development of novel NNRTIs, we set out to explore new territory in NNRTI drug design with a goal of maintaining efficacy in the presence of both wild-type and mutated forms of HIV-1. To this end we designed three different NNRTI scaffolds along three different research thrusts. The first of these focused on the synthesis of 15 novel flexible triazole containing compounds. With these compounds we sought to achieve π-π stacking interactions with conserved amino acid residue Trp229 in the hope that we would be able to maintain efficacy in the presence of mutated forms of the virus. An additional feature included hydrogen bonding interactions to the backbone of Lys103. However, despite having thoroughly explored the triazole ring with multiple substitution arrangements, these compounds had very poor to no activity against whole cell HIV-1. Secondly we focused on the synthesis of a 4-hydroxyindole scaffold as a potential NNRTI. The focus here was to achieve interactions to Trp229 and simultaneously achieve hydrogen bonding interactions to the backbone of Lys101 at the entrance of the pocket. This was a novel concept in this class of compounds. We were able to successfully synthesize the indole core as a proofof-concept using the Knoevenagel-Hemetsberger method however; this compound had no activity against HIV-1. Lastly, in our quest to synthesize a novel NNRTI that could maintain efficacy against HIV-1 we decided to attempt to improve upon the stability of a lead indole-based compound synthesized previously within our research group. The lead compound was found to be potent with an IC50 of 1 nM but was unstable in acidic media due to the presence of a methoxy functionality situated at the 3-position on the indole. We sought to overcome this issue by introducing a substituted aryl amine functionality at this position. We were successful in synthesizing our desired compound but unfortunately it was significantly less active against whole cell HIV-1 than the lead compound. However,… Advisors/Committee Members: Pelly, Stephen Christopher, van Otterlo, Willem Arjen Lodewijk, Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science..

Subjects/Keywords: Reverse transcriptase – Inhibitors; HIV (Viruses); UCTD

…consists of two nucleoside reverse transcriptase inhibitors (NRTIs) or nucleotide… …reverse transcriptase inhibitors (NtRTIs) in combination with either a non-nucleoside… …Nucleoside Reverse Transcriptase Inhibitors (NRTIs) The oldest class of antiretrovirals… …are nucleoside reverse transcriptase inhibitors (NRTIs) which target the… …Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) 1.5.1. Allosteric…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pribut, N. (2015). The design and synthesis of novel HIV-1 non-nucleoside reverse transcriptase inhibitors. (Masters Thesis). Stellenbosch University. Retrieved from http://hdl.handle.net/10019.1/96693

Chicago Manual of Style (16^th Edition):

Pribut, Nicole. “The design and synthesis of novel HIV-1 non-nucleoside reverse transcriptase inhibitors.” 2015. Masters Thesis, Stellenbosch University. Accessed March 08, 2021. http://hdl.handle.net/10019.1/96693.

MLA Handbook (7^th Edition):

Pribut, Nicole. “The design and synthesis of novel HIV-1 non-nucleoside reverse transcriptase inhibitors.” 2015. Web. 08 Mar 2021.

Vancouver:

Pribut N. The design and synthesis of novel HIV-1 non-nucleoside reverse transcriptase inhibitors. [Internet] [Masters thesis]. Stellenbosch University; 2015. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/10019.1/96693.

Council of Science Editors:

Pribut N. The design and synthesis of novel HIV-1 non-nucleoside reverse transcriptase inhibitors. [Masters Thesis]. Stellenbosch University; 2015. Available from: http://hdl.handle.net/10019.1/96693

14. Selyutina, Anastasia. When biologist meets chemist: a search for HIV-1 inhibitors .

Degree: 2015, Tartu University

URL: http://hdl.handle.net/10062/49136

► HIV-1 on pandeemiline viirus ning nakatatud inimeste arv maailmas suureneb pidevalt. Vaktsiin selle vastu puudub, kuid nakatatud patsientide raviks on kliinilise kasutuse loa saanud ligi… (more)

▼ HIV-1 on pandeemiline viirus ning nakatatud inimeste arv maailmas suureneb pidevalt. Vaktsiin selle vastu puudub, kuid nakatatud patsientide raviks on kliinilise kasutuse loa saanud ligi 30 erinevat ühendit. Erinevatesse klassidesse kuuluvate inhibiitorite kombineeritud kasutamine (ART) on kujunenud HIV-ga nakatunud patsientide ravimise aluseks. ART ravi kõige olulisemaks puuduseks on ravimite toksilised kõrvaltoimed ning uute resistentsete viiruse tüvede teke. Antud väitekirja põhieesmärgiks oli leida efektiivseid mittetoksilisi ühendeid, mis suruvad maha HIV-1 replikatsiooni (nii metsik-tüüpi viiruse kui ka resistentsete tüvede oma) keskendudes eelkõige pöördtranskriptaasi inhibiitoritele. Kolm gruppi keemilisi ühendeid testiti antiretroviirus-vastase toime suhtes: atsüklilised tümidiini nukleosiidi analoogid, bimorfoliinid ja nende derivaadid ning sahariidhüdrasoonid. Samuti tõestati eksperimentaalselt eelneva in silico skriiningu käigus saadud tulemusi. Käesoleva töö tulemusena töötati välja meetod HIV-1 inhibiitorite skriinimiseks ViraPower lentiviiruse ekspressioonisüsteemi (Invitrogen) põhjal. Meetod on kiire, lihtne, usaldusväärne ning on kõlblik kasutamiseks väljaspool kõrgenenud ohutustasemega laborit (BSL3). Kõige tugevam toime meie laboris uuritud ühenditest oli mitte-nukleosiidsel pöördtranskriptaasi inhibiitoril (NNRTI), mis omas tuntud ravimi Nevirapiiniga sarnast aktiivsust, kuid oli kahjuks mitteaktiivne viiruse resistentsete vormide vastu. Antud ühend leiti ratsionaalse ravimidisaini strateegiat kasutades. Antud töö tulemused võimaldasid täiustada olemasolevat in silico skriiningu meetodit, mis võimaldab tulevikus kavandada uusi ning efektiivsemaid HIV-1 inhibiitoreid.; HIV-1 is a pandemic virus and the numbers of infected people are constantly increasing all over the world. There is no vaccine available, but about 30 compounds have been approved by FDA for the treatment of HIV-infected patients. ART (antiretroviral therapy) consists of a combination of at least 3 inhibitors with different mechanism of action. The main drawback of such treatment is side effects of the drugs and the appearance of new resistant forms of the virus. The aim of this work was to find non-toxic compounds which can effectively suppress HIV-1 replication (both wild-type and resistant forms of the virus). We focused our efforts mostly on the discovery of novel reverse transcriptase inhibitors. Three groups of compounds were tested for their antiretroviral activity (acyclic thymine nucleoside analogues, bimorpholines and their derivatives, and saccharide hydrazones); also we experimentally verified the results of the previous in silico screening. As a result of this work, we developed an assay for HIV-1 inhibitors′ screening. This assay is based on ViraPower Lentiviral Expression System (Invitrogen) and is simple, fast, reliable and can be used outside BSL3 facilities. The most potent compound, found by us so far, acts as a non-nucleoside reverse transcriptase inhibitor (NNRTI) and has activity comparable to the…

Subjects/Keywords: HIV-nakkused; HIV-1; pöördtranskriptaas; ensüümiinhibiitorid; antiviiruslik aktiivsus; HIV-infections; HIV-1; reverse transcriptase; enzyme inhibitors; antiviral activity

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Selyutina, A. (2015). When biologist meets chemist: a search for HIV-1 inhibitors . (Thesis). Tartu University. Retrieved from http://hdl.handle.net/10062/49136

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Selyutina, Anastasia. “When biologist meets chemist: a search for HIV-1 inhibitors .” 2015. Thesis, Tartu University. Accessed March 08, 2021. http://hdl.handle.net/10062/49136.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Selyutina, Anastasia. “When biologist meets chemist: a search for HIV-1 inhibitors .” 2015. Web. 08 Mar 2021.

Vancouver:

Selyutina A. When biologist meets chemist: a search for HIV-1 inhibitors . [Internet] [Thesis]. Tartu University; 2015. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/10062/49136.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Selyutina A. When biologist meets chemist: a search for HIV-1 inhibitors . [Thesis]. Tartu University; 2015. Available from: http://hdl.handle.net/10062/49136

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Aristotle University Of Thessaloniki (AUTH); Αριστοτέλειο Πανεπιστήμιο Θεσσαλονίκης (ΑΠΘ)

15. Petrou, Anthi. Σχεδιασμός, σύνθεση και μελέτη βιολογικής δράσης νέων θειαζολικών παραγώγων.

Degree: 2020, Aristotle University Of Thessaloniki (AUTH); Αριστοτέλειο Πανεπιστήμιο Θεσσαλονίκης (ΑΠΘ)

URL: http://hdl.handle.net/10442/hedi/47091

►

This work presents and discusses the design and synthesis of 54 novel 2, 3-aryl-thiazolidin-4-ones, with increased activity against human immunodeficiency virus (HIV). HIV is the… (more)

▼

This work presents and discusses the design and synthesis of 54 novel 2, 3-aryl-thiazolidin-4-ones, with increased activity against human immunodeficiency virus (HIV). HIV is the causative agent of the Acquired Immunodeficiency Syndrome (AIDS), an infectious disease with increasing incidence worldwide. Non-nucleoside reverse transcriptase inhibitors or NNRTIs play an important role in the treatment of AIDS. However, despite the fact that many compounds are already used as anti-HIV drugs, research into the development of new inhibitors continues as the virus develops resistant strains, limiting their use. Taking into account the best features of available NNRTIs and with the aid of Molecular docking studies, it is attempted to synthesize new compounds that will not be blocked by small mutations in the reserve transcriptase (RT) binding domain, but they will exhibit a large number of interactions with RT by enhancing their anti-HIV-activity. The synthesis of the selected compounds was carried out by one-pot reaction of the appropriate heteroaromatic amine with a substituted benzaldehyde and thioglycolic acid. Identification of the products was performed using spectroscopic methods (IR, 1H-NMR, 13C-NMR and MS).Finally, an in vitro study of the inhibitory activity of the new compounds on HIV-1 RT was performed using both the immunoenzymatic colorimetric and the radioisotope methods.Molecular docking studies were carried out to enable the design of new HIV-1 RT inhibitors. The binding free energies of compounds to HIV-1 RT were found to have a good correlation with the experimental inhibitory activities. The most favorable binding mode of top-ranking compounds will be useful in designing new NNRTIs.Finally, due to the importance of antimicrobial drugs for the treatment of many microbial infections in immunocompromised patients, such as those with AIDS, in vitro studies were performed to test the antimicrobial activity of the compounds, followed by docking studies for the prediction of the most potent mechanism of antimicrobial action.

Στην παρούσα διδακτορική διατριβή επιχειρείται ο σχεδιασμός και η σύνθεση νέων ενώσεων, με αυξημένη δράση κατά του ιού της ανθρώπινης ανοσοανεπάρκειας (HIV). Ο ιός HIV είναι ο αιτιολογικός παράγων του Συνδρόμου Επίκτητης Ανοσολογικής Ανεπάρκειας (AIDS), μιας λοιμώδης νόσου με αυξανόμενη επίπτωση παγκοσμίως. Οι μη νουκλεοσιδικοί αναστολείς της αντίστροφης μεταγραφάσης (RT) ή NNRTIs διαδραματίζουν σημαντικό ρόλο στην θεραπεία του AIDS. Ωστόσο, παρά το γεγονός ότι πολλές ενώσεις χρησιμοποιούνται ήδη ως φάρμακα κατά του HIV, η έρευνα για την ανάπτυξη νέων αναστολέων συνεχίζεται, καθώς ο ιός αναπτύσσει ανθεκτικά στελέχη, περιορίζοντας την χρησιμοποίησή τους. Λαμβάνοντας υπόψη τα καλύτερα χαρακτηριστικά των διαθέσιμων NNRTIs από την βιβλιογραφία και με τη βοήθεια in silico μελετών πρόσδεσης (Docking) καθώς και του υπολογιστικού προγράμματος πρόβλεψης της βιολογικής δράσης PASS, επιχειρείται ο σχεδιασμός και η σύνθεση νέων ενώσεων που δεν θα εμποδίζονται από μικρές μεταλλάξεις στην περιοχή…

Subjects/Keywords: Οργανική σύνθεση; Θειαζολιδινόνες; Σύνδρομο επίκτητης ανοσολογικής ανεπάρκειας - AIDS; Σχεδιασμός φαρμάκων; Organic synthesis; Molecular docking; Computer aided drug design; Reverse transcriptase inhibitors

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Petrou, A. (2020). Σχεδιασμός, σύνθεση και μελέτη βιολογικής δράσης νέων θειαζολικών παραγώγων. (Thesis). Aristotle University Of Thessaloniki (AUTH); Αριστοτέλειο Πανεπιστήμιο Θεσσαλονίκης (ΑΠΘ). Retrieved from http://hdl.handle.net/10442/hedi/47091

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Petrou, Anthi. “Σχεδιασμός, σύνθεση και μελέτη βιολογικής δράσης νέων θειαζολικών παραγώγων.” 2020. Thesis, Aristotle University Of Thessaloniki (AUTH); Αριστοτέλειο Πανεπιστήμιο Θεσσαλονίκης (ΑΠΘ). Accessed March 08, 2021. http://hdl.handle.net/10442/hedi/47091.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Petrou, Anthi. “Σχεδιασμός, σύνθεση και μελέτη βιολογικής δράσης νέων θειαζολικών παραγώγων.” 2020. Web. 08 Mar 2021.

Vancouver:

Petrou A. Σχεδιασμός, σύνθεση και μελέτη βιολογικής δράσης νέων θειαζολικών παραγώγων. [Internet] [Thesis]. Aristotle University Of Thessaloniki (AUTH); Αριστοτέλειο Πανεπιστήμιο Θεσσαλονίκης (ΑΠΘ); 2020. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/10442/hedi/47091.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Petrou A. Σχεδιασμός, σύνθεση και μελέτη βιολογικής δράσης νέων θειαζολικών παραγώγων. [Thesis]. Aristotle University Of Thessaloniki (AUTH); Αριστοτέλειο Πανεπιστήμιο Θεσσαλονίκης (ΑΠΘ); 2020. Available from: http://hdl.handle.net/10442/hedi/47091

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Rochester

16. Operario, Darwin Joseph. The RT-dNTP interaction as a determinant for generation of retroviral genomic diversity and cell-type specificity.

Degree: PhD, 2009, University of Rochester

URL: http://hdl.handle.net/1802/6525

► Retroviruses contain two copies of a positive-sense single stranded RNA genome. Uniquely amongst RNA viruses, the retroviral lifecycle involves the replication of these RNA genomes… (more)

Subjects/Keywords: Reverse transcriptase

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APA (6^th Edition):

Operario, D. J. (2009). The RT-dNTP interaction as a determinant for generation of retroviral genomic diversity and cell-type specificity. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/6525

Chicago Manual of Style (16^th Edition):

Operario, Darwin Joseph. “The RT-dNTP interaction as a determinant for generation of retroviral genomic diversity and cell-type specificity.” 2009. Doctoral Dissertation, University of Rochester. Accessed March 08, 2021. http://hdl.handle.net/1802/6525.

MLA Handbook (7^th Edition):

Operario, Darwin Joseph. “The RT-dNTP interaction as a determinant for generation of retroviral genomic diversity and cell-type specificity.” 2009. Web. 08 Mar 2021.

Vancouver:

Operario DJ. The RT-dNTP interaction as a determinant for generation of retroviral genomic diversity and cell-type specificity. [Internet] [Doctoral dissertation]. University of Rochester; 2009. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1802/6525.

Council of Science Editors:

Operario DJ. The RT-dNTP interaction as a determinant for generation of retroviral genomic diversity and cell-type specificity. [Doctoral Dissertation]. University of Rochester; 2009. Available from: http://hdl.handle.net/1802/6525

Rutgers University

17. Frahm, Stephanie A., 1983-. Functional quality control for human blood-based gene expression products.

Degree: MS, Microbiology and Molecular Genetics, 2012, Rutgers University

URL: http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000064089

► Reliable and robust gene expression data generated by microarrays or quantitative real-time polymerase chain reaction (qPCR) is directly dependent upon use of high-quality input material,… (more)

▼ Reliable and robust gene expression data generated by microarrays or quantitative real-time polymerase chain reaction (qPCR) is directly dependent upon use of high-quality input material, namely high caliber cDNA generated from intact, non-degraded RNA. Due to its labile nature, the integrity of RNA can be jeopardized at multiple points during sample collection, extraction, and storage, adversely affecting downstream gene expression data interpretation and discovery. Accurately assessing RNA and cDNA quality prior to gene expression analysis proves to be a critical step requiring a highly sensitive and specific quality control method. Existing industry-standard RNA quality control techniques rely on microcapillary electrophoresis, which provides an analytical assessment of ribosomal RNA (rRNA) integrity. While providing a gross evaluation of total RNA quality using rRNA as a surrogate, these methods fail to adequately predict the downstream functional performance of messenger RNA (mRNA), the class of RNA used to study gene expression. Conversely, real-time qPCR offers a sensitive functional quality control tool for evaluating mRNA integrity and predicting future performance on gene expression platforms by directly evaluating cDNA functionality. Design of tissue-specific assay panels targeting a select set of genes provides a focused and versatile solution, which is lacking in broad-spectrum microcapillary electrophoresis analysis methods. Furthermore, qPCR assays offer high-throughput laboratories and biorepositories an efficient and automatable quality control screening method. By taking advantage of regional degradation patterns of RNA, class prediction algorithms can be developed for individual assays to measure RNA quality as a function of the magnitude of deviation from an expected gene expression value, or CT value. By determining the degree of shift from an expected CT value for each assay in the panel, individual algorithm outputs can be collectively evaluated to determine an overall RNA quality score, allowing researchers to properly weight or exclude subpar samples from analysis. The following work describes the ongoing development of a novel functional quality control method for RNA samples extracted from human whole blood, consisting of a custom gene expression assay panel and complementary class prediction algorithms. Advisors/Committee Members: Frahm, Stephanie A., 1983- (author), Brooks, Andrew I (chair), Tischfield, Jay A (internal member), Matise, Tara C (internal member).

Subjects/Keywords: RNA; Reverse transcriptase; Gene expression

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APA (6^th Edition):

Frahm, Stephanie A., 1. (2012). Functional quality control for human blood-based gene expression products. (Masters Thesis). Rutgers University. Retrieved from http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000064089

Chicago Manual of Style (16^th Edition):

Frahm, Stephanie A., 1983-. “Functional quality control for human blood-based gene expression products.” 2012. Masters Thesis, Rutgers University. Accessed March 08, 2021. http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000064089.

MLA Handbook (7^th Edition):

Frahm, Stephanie A., 1983-. “Functional quality control for human blood-based gene expression products.” 2012. Web. 08 Mar 2021.

Vancouver:

Frahm, Stephanie A. 1. Functional quality control for human blood-based gene expression products. [Internet] [Masters thesis]. Rutgers University; 2012. [cited 2021 Mar 08]. Available from: http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000064089.

Council of Science Editors:

Frahm, Stephanie A. 1. Functional quality control for human blood-based gene expression products. [Masters Thesis]. Rutgers University; 2012. Available from: http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000064089

University of Missouri – Columbia

18. Schuckmann, Matthew M. Characterization of HIV-1 reverse transcriptase drug resistance connection subdomain mutation N348I.

Degree: 2011, University of Missouri – Columbia

URL: http://hdl.handle.net/10355/14917

► [ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Connection subdomain mutations are a recently discovered class of reverse transcriptase (RT) drug resistance… (more)

▼ [ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Connection subdomain mutations are a recently discovered class of reverse transcriptase (RT) drug resistance mutations which are positioned at some distance from previously described resistance mutations. The work presented in this thesis investigates drug resistance mechanisms conferred by HIV-1 RT connection subdomain mutation N348I. N348I was chosen as a representative connection subdomain mutation due to its clinical relevance to resistance against drugs belonging to both classes of HIV-1 RT inhibitors: the NRTIs and NNRTIs. N348I is the first, and currently only, clinically relevant HIV-1 RT single amino acid substitution mutation known to confer cross-resistance to drugs from both classes of RT inhibitors. I describe here a mechanism of HIV-1 RT N348I in vitro resistance against inhibition by the NNRTI nevirapine (NVP), where I show the mutant enzyme exhibits a decreased affinity towards inhibitor binding. Using pre-steady state kinetics techniques, I further show in detail how the N348I mutation on either of the heterodimer enzyme's subunits affects enzymatic activities. Interestingly, the mutation on either subunit decreases the rate of catalytic turnover for nucleotide incorporation reactions. The N348I mutant enzyme also displays an altered RNAse H activity, and I demonstrate that the N348I mutation on the p51 subunit provides the major contribution towards this altered activity. I also investigated RT N348I in vitro susceptibility to ddATP, the active form of the NRTI prodrug didanosine (ddI). Multiple mechanisms of NRTI resistance were studied, but significant levels of in vitro resistance to ddATP were not detected despite the fact that the N34I mutant virus has been shown to be resistant to ddI. Here I found that the N348I mutation does not negatively impact the steady-state kinetics of single nucleotide incorporation reactions, or the affinity for nucleotide substrate. Advisors/Committee Members: Burke, Donald H. (advisor).

Subjects/Keywords: viral drug resistance; retroviral inhibitors; enzymology; DNA polymerase; RNase H; Drug Resistance, Viral – drug effects; HIV-1 – drug effects; HIV Reverse Transcriptase; Reverse Transcriptase Inhibitors; Ribonuclease H; Nevirapine; Mutation, Missense; Drug Resistance, Viral – genetics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Schuckmann, M. M. (2011). Characterization of HIV-1 reverse transcriptase drug resistance connection subdomain mutation N348I. (Thesis). University of Missouri – Columbia. Retrieved from http://hdl.handle.net/10355/14917

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Schuckmann, Matthew M. “Characterization of HIV-1 reverse transcriptase drug resistance connection subdomain mutation N348I.” 2011. Thesis, University of Missouri – Columbia. Accessed March 08, 2021. http://hdl.handle.net/10355/14917.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Schuckmann, Matthew M. “Characterization of HIV-1 reverse transcriptase drug resistance connection subdomain mutation N348I.” 2011. Web. 08 Mar 2021.

Vancouver:

Schuckmann MM. Characterization of HIV-1 reverse transcriptase drug resistance connection subdomain mutation N348I. [Internet] [Thesis]. University of Missouri – Columbia; 2011. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/10355/14917.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Schuckmann MM. Characterization of HIV-1 reverse transcriptase drug resistance connection subdomain mutation N348I. [Thesis]. University of Missouri – Columbia; 2011. Available from: http://hdl.handle.net/10355/14917

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Hong Kong

19. Lu, Xiaofan. Mechanism study of a small molecule F18 as a novel anti-HIV-1 non-nucleoside reverse transcriptase inhibitor.

Degree: 2012, University of Hong Kong

URL: http://hdl.handle.net/10722/146137

► Non-nucleoside reverse transcriptase inhibitor (NNRTI) is one of the key components of antiretroviral drug regimen against human immunodeficiency virus type-1 (HIV-1) replication. However, the low… (more)

▼ Non-nucleoside reverse transcriptase inhibitor (NNRTI) is one of the key components of antiretroviral drug regimen against human immunodeficiency virus type-1 (HIV-1) replication. However, the low genetic barriers to drug-resistance or cross-resistance, side effects, as well as the unaffordable cost of NNRTIs compromise their clinical usage. Therefore, to develop novel NNRTIs with potent antiviral activity against HIV-1 becomes a major concern in the treatment and prevention of HIV/AIDS. (+)-Calanolide A, which is a natural product initially extracted from the tropical rainforest tree Calophyllum lanigerum, was identified as an attractive NNRTI against HIV-1 despite virus strains containing drug-resistant K103N/Y181C mutations. In this study, a chemical library was constructed based on the three chiral carbon centers of (+)-Calanolide A. After screening the activity against HIVNL4-3 wild-type and several NNRTI-resistant pseudoviruses, a small molecule 10-chloromethyl-11- demethyl-12-oxo-calanolide A (F18) was identified as novel NNRTI with promising anti-HIV efficacy. Further studies were performed to investigate the antiviral breadth, drug resistance profile and underlying mechanism of the action of F18. F18 consistently displayed a potent activity against primary HIV-1 isolates including various subtypes of M group, CRF01_AE, and laboratory-adapted drug-resistant viruses in PBMC based assay. Moreover, F18 displayed distinct profiles against 17 NNRTI-resistant pseudoviruses, with an excellent potency especially against one of the most prevalent strains with the Y181C mutation (EC50=1.0nM) in cell line based assay, which was in stark contrast from the extensively used NNRTIs nevirapine and efavirenz. F18-resistant viruses were induced by in vitro serial passages, and mutation L100I was appeared to be the dominant contributor to F18-resistance, further suggesting a binding motif different from nevirapine and efavirenz. The efficacy of F18 was non-antagonistic when used in combination with other antiretrovirals against both wild-type and drug-resistant viruses in infected PBMCs. Interestingly, F18 displayed a highly synergistic antiviral effect with nevirapine against nevirapine-resistant virus (Y181C). Furthermore, in silico docking analysis suggested that F18 may bind to the HIV-1 reverse transcriptase in a way different to other NNRTIs. For the potential as an anti-HIV-1 microbicide, F18 also showed the stable and rapid release, as well as the sustained antiviral activity against HIV-1 wild-type virus in a formulation temperature-sensitive acidic gel. In summary, this study presents F18 as a new potential drug for clinical use and also underlies new mechanism-based design for future NNRTI. Advisors/Committee Members: Chen, Z (advisor), Zheng, B (advisor).

Subjects/Keywords: AIDS (Disease) - Chemotherapy.; Antiretroviral agents.; Reverse transcriptase - Inhibitors - Therapeutic use.; HIV infections - Chemotherapy.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lu, X. (2012). Mechanism study of a small molecule F18 as a novel anti-HIV-1 non-nucleoside reverse transcriptase inhibitor. (Thesis). University of Hong Kong. Retrieved from http://hdl.handle.net/10722/146137

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lu, Xiaofan. “Mechanism study of a small molecule F18 as a novel anti-HIV-1 non-nucleoside reverse transcriptase inhibitor.” 2012. Thesis, University of Hong Kong. Accessed March 08, 2021. http://hdl.handle.net/10722/146137.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lu, Xiaofan. “Mechanism study of a small molecule F18 as a novel anti-HIV-1 non-nucleoside reverse transcriptase inhibitor.” 2012. Web. 08 Mar 2021.

Vancouver:

Lu X. Mechanism study of a small molecule F18 as a novel anti-HIV-1 non-nucleoside reverse transcriptase inhibitor. [Internet] [Thesis]. University of Hong Kong; 2012. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/10722/146137.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lu X. Mechanism study of a small molecule F18 as a novel anti-HIV-1 non-nucleoside reverse transcriptase inhibitor. [Thesis]. University of Hong Kong; 2012. Available from: http://hdl.handle.net/10722/146137

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Arizona State University

20. Brown, Andrew. Exploring the Regulation of the Telomerase Reaction Cycle through Unique Protein, DNA, and RNA Interactions.

Degree: PhD, Chemistry, 2014, Arizona State University

URL: http://repository.asu.edu/items/25104

► Telomerase is a unique reverse transcriptase that has evolved specifically to extend the single stranded DNA at the 3' ends of chromosomes. To achieve this,… (more)

Subjects/Keywords: Biochemistry; Molecular biology; Reverse transcriptase; Ribonucleoprotein; Telomerase

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APA (6^th Edition):

Brown, A. (2014). Exploring the Regulation of the Telomerase Reaction Cycle through Unique Protein, DNA, and RNA Interactions. (Doctoral Dissertation). Arizona State University. Retrieved from http://repository.asu.edu/items/25104

Chicago Manual of Style (16^th Edition):

Brown, Andrew. “Exploring the Regulation of the Telomerase Reaction Cycle through Unique Protein, DNA, and RNA Interactions.” 2014. Doctoral Dissertation, Arizona State University. Accessed March 08, 2021. http://repository.asu.edu/items/25104.

MLA Handbook (7^th Edition):

Brown, Andrew. “Exploring the Regulation of the Telomerase Reaction Cycle through Unique Protein, DNA, and RNA Interactions.” 2014. Web. 08 Mar 2021.

Vancouver:

Brown A. Exploring the Regulation of the Telomerase Reaction Cycle through Unique Protein, DNA, and RNA Interactions. [Internet] [Doctoral dissertation]. Arizona State University; 2014. [cited 2021 Mar 08]. Available from: http://repository.asu.edu/items/25104.

Council of Science Editors:

Brown A. Exploring the Regulation of the Telomerase Reaction Cycle through Unique Protein, DNA, and RNA Interactions. [Doctoral Dissertation]. Arizona State University; 2014. Available from: http://repository.asu.edu/items/25104

University of Georgia

21. Underwood, Dana Elizabeth Hager. A genetic analysis of telomerase translocation and telomere function in L. lactis.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/20694

► Telomeres are DNA-protein complexes that protect the ends of linear chromosomes. The non-genic DNA is typically composted of repetitive T/G-rich sequences, and maintained by telomerase,… (more)

▼ Telomeres are DNA-protein complexes that protect the ends of linear chromosomes. The non-genic DNA is typically composted of repetitive T/G-rich sequences, and maintained by telomerase, a specialized reverse transcriptase. In the yeast K. lactis, the telomeric repeats are 25 base-pairs in length and copied from a 30 nucleotide template within the telomerase ribonucleoprotein complex. In order to examine the functional regions contained within the telomere and the telomerase template, strains were constructed such that each contained a single base change in the region of the TER1 gene encoding the telomerase template. Mutations were made at all 30 template positions, and the effects were initially examined by measuring the lengths of the telomeres in the mutant yeast. Telomeres were also cloned to examine the types of mutant telomeric repeats added by telomerase. Typically, the mutations were incorporated as single base-changes in the newly synthesized telomeric repeat. Mutations leading to telomere elongation, telomere shortening, delayed telomere elongation, and telomeric repeats of aberrant sizes were identified. Mutations causing each phenotype were often confined to discrete regions of the template. Mutations leading to telomere elongation and aberrantly sized telomeric repeats were examined further. Extreme telomere elongation was found to be independent of RAD52-dependent recombination. However, the formation of the large amount of extrachromosomal and single-stranded telomeric DNA observed in these mutants was found to be dependent on RAD52. Subtelomeric recombination was also found to be elevated in these mutants. Mutations in the ends of the telomerase template led to the synthesis of telomeric repeats that were not 25 base-pairs in length. By examining the telomeric repeats in these mutants, it was determined that mutations which disrupted the base-pairing between the telomere and the template that occurs prior to the synthesis of new telomeric repeats caused the telomere to align with a different region of the template. Mismatches, therefore, were typically neither extended nor removed by a nucleolytic activity. It was also determined that a region outside of the template might play a role in stabilizing the base-pairing interactions between the telomere and the template prior to the synthesis of new telomeric repeats.

Subjects/Keywords: Telomere; Telomerase; Repeat; Reverse transcriptase; Ribonucleoprotein; RAD52

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Underwood, D. E. H. (2014). A genetic analysis of telomerase translocation and telomere function in L. lactis. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/20694

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Underwood, Dana Elizabeth Hager. “A genetic analysis of telomerase translocation and telomere function in L. lactis.” 2014. Thesis, University of Georgia. Accessed March 08, 2021. http://hdl.handle.net/10724/20694.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Underwood, Dana Elizabeth Hager. “A genetic analysis of telomerase translocation and telomere function in L. lactis.” 2014. Web. 08 Mar 2021.

Vancouver:

Underwood DEH. A genetic analysis of telomerase translocation and telomere function in L. lactis. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/10724/20694.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Underwood DEH. A genetic analysis of telomerase translocation and telomere function in L. lactis. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/20694

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Missouri – Columbia

22. Flores, Jacqueline A. Biochemical characterization of clade B and non-B HIV-1 reverse transcriptase.

Degree: 2017, University of Missouri – Columbia

URL: http://hdl.handle.net/10355/62017

► [ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Two classes of drugs: nucleos(t)ide reverse transcriptase inhibitors (NRTIs) and non-nucleoside RT inhibitors (NNRTIs)… (more)

Subjects/Keywords: Reverse transcriptase; Drug resistance; HIV (Viruses)

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APA (6^th Edition):

Flores, J. A. (2017). Biochemical characterization of clade B and non-B HIV-1 reverse transcriptase. (Thesis). University of Missouri – Columbia. Retrieved from http://hdl.handle.net/10355/62017

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Flores, Jacqueline A. “Biochemical characterization of clade B and non-B HIV-1 reverse transcriptase.” 2017. Thesis, University of Missouri – Columbia. Accessed March 08, 2021. http://hdl.handle.net/10355/62017.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Flores, Jacqueline A. “Biochemical characterization of clade B and non-B HIV-1 reverse transcriptase.” 2017. Web. 08 Mar 2021.

Vancouver:

Flores JA. Biochemical characterization of clade B and non-B HIV-1 reverse transcriptase. [Internet] [Thesis]. University of Missouri – Columbia; 2017. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/10355/62017.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Flores JA. Biochemical characterization of clade B and non-B HIV-1 reverse transcriptase. [Thesis]. University of Missouri – Columbia; 2017. Available from: http://hdl.handle.net/10355/62017

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Rutgers University

23. Hammond, Gifty Naa Ayeley, 1981-. Defining the nanoRNA regulon and the mechanism by which gene expression is controlled and manifested.

Degree: MS, Microbiology and Molecular Genetics, 2014, Rutgers University

URL: https://rucore.libraries.rutgers.edu/rutgers-lib/42394/

► Gene transcription is mediated by the enzyme RNA polymerase (RNAP). RNAP is a multi subunit nucleotidyl transferase that polymerizes ribonucleotides at the 3’ end of… (more)

Subjects/Keywords: Gene expression; Genetic regulation; Reverse transcriptase

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APA (6^th Edition):

Hammond, Gifty Naa Ayeley, 1. (2014). Defining the nanoRNA regulon and the mechanism by which gene expression is controlled and manifested. (Masters Thesis). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/42394/

Chicago Manual of Style (16^th Edition):

Hammond, Gifty Naa Ayeley, 1981-. “Defining the nanoRNA regulon and the mechanism by which gene expression is controlled and manifested.” 2014. Masters Thesis, Rutgers University. Accessed March 08, 2021. https://rucore.libraries.rutgers.edu/rutgers-lib/42394/.

MLA Handbook (7^th Edition):

Hammond, Gifty Naa Ayeley, 1981-. “Defining the nanoRNA regulon and the mechanism by which gene expression is controlled and manifested.” 2014. Web. 08 Mar 2021.

Vancouver:

Hammond, Gifty Naa Ayeley 1. Defining the nanoRNA regulon and the mechanism by which gene expression is controlled and manifested. [Internet] [Masters thesis]. Rutgers University; 2014. [cited 2021 Mar 08]. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/42394/.

Council of Science Editors:

Hammond, Gifty Naa Ayeley 1. Defining the nanoRNA regulon and the mechanism by which gene expression is controlled and manifested. [Masters Thesis]. Rutgers University; 2014. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/42394/

Universiteit Utrecht

24. Kappelhoff, B.S. Clinical pharmacological investigations of antiretroviral drugs.

Degree: 2005, Universiteit Utrecht

URL: http://dspace.library.uu.nl:8080/handle/1874/29727

► The major aim of all studies described in this thesis is to contribute to the optimisation of antiretroviral drug treatment in HIV-infected patients by the… (more)

Subjects/Keywords: Farmacie; HIV; antiretroviral drugs; non-nucleoside reverse transcriptase inhibitor; NNRTI; protease inhibitor; PI; (population) pharmacokinetics; (clinical) pharmacology; NONMEM; bioanalysis; 2NN study

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kappelhoff, B. S. (2005). Clinical pharmacological investigations of antiretroviral drugs. (Doctoral Dissertation). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/29727

Chicago Manual of Style (16^th Edition):

Kappelhoff, B S. “Clinical pharmacological investigations of antiretroviral drugs.” 2005. Doctoral Dissertation, Universiteit Utrecht. Accessed March 08, 2021. http://dspace.library.uu.nl:8080/handle/1874/29727.

MLA Handbook (7^th Edition):

Kappelhoff, B S. “Clinical pharmacological investigations of antiretroviral drugs.” 2005. Web. 08 Mar 2021.

Vancouver:

Kappelhoff BS. Clinical pharmacological investigations of antiretroviral drugs. [Internet] [Doctoral dissertation]. Universiteit Utrecht; 2005. [cited 2021 Mar 08]. Available from: http://dspace.library.uu.nl:8080/handle/1874/29727.

Council of Science Editors:

Kappelhoff BS. Clinical pharmacological investigations of antiretroviral drugs. [Doctoral Dissertation]. Universiteit Utrecht; 2005. Available from: http://dspace.library.uu.nl:8080/handle/1874/29727

25. Kappelhoff, B.S. Clinical pharmacological investigations of antiretroviral drugs.

Degree: 2005, University Utrecht

URL: https://dspace.library.uu.nl/handle/1874/29727 ; URN:NBN:NL:UI:10-1874-29727 ; 1874/29727 ; urn:isbn:9039339317 ; URN:NBN:NL:UI:10-1874-29727 ; https://dspace.library.uu.nl/handle/1874/29727

► The major aim of all studies described in this thesis is to contribute to the optimisation of antiretroviral drug treatment in HIV-infected patients by the… (more)

Subjects/Keywords: HIV; antiretroviral drugs; non-nucleoside reverse transcriptase inhibitor; NNRTI; protease inhibitor; PI; (population) pharmacokinetics; (clinical) pharmacology; NONMEM; bioanalysis; 2NN study

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kappelhoff, B. S. (2005). Clinical pharmacological investigations of antiretroviral drugs. (Doctoral Dissertation). University Utrecht. Retrieved from https://dspace.library.uu.nl/handle/1874/29727 ; URN:NBN:NL:UI:10-1874-29727 ; 1874/29727 ; urn:isbn:9039339317 ; URN:NBN:NL:UI:10-1874-29727 ; https://dspace.library.uu.nl/handle/1874/29727

Chicago Manual of Style (16^th Edition):

Kappelhoff, B S. “Clinical pharmacological investigations of antiretroviral drugs.” 2005. Doctoral Dissertation, University Utrecht. Accessed March 08, 2021. https://dspace.library.uu.nl/handle/1874/29727 ; URN:NBN:NL:UI:10-1874-29727 ; 1874/29727 ; urn:isbn:9039339317 ; URN:NBN:NL:UI:10-1874-29727 ; https://dspace.library.uu.nl/handle/1874/29727.

MLA Handbook (7^th Edition):

Kappelhoff, B S. “Clinical pharmacological investigations of antiretroviral drugs.” 2005. Web. 08 Mar 2021.

Vancouver:

Kappelhoff BS. Clinical pharmacological investigations of antiretroviral drugs. [Internet] [Doctoral dissertation]. University Utrecht; 2005. [cited 2021 Mar 08]. Available from: https://dspace.library.uu.nl/handle/1874/29727 ; URN:NBN:NL:UI:10-1874-29727 ; 1874/29727 ; urn:isbn:9039339317 ; URN:NBN:NL:UI:10-1874-29727 ; https://dspace.library.uu.nl/handle/1874/29727.

Council of Science Editors:

Kappelhoff BS. Clinical pharmacological investigations of antiretroviral drugs. [Doctoral Dissertation]. University Utrecht; 2005. Available from: https://dspace.library.uu.nl/handle/1874/29727 ; URN:NBN:NL:UI:10-1874-29727 ; 1874/29727 ; urn:isbn:9039339317 ; URN:NBN:NL:UI:10-1874-29727 ; https://dspace.library.uu.nl/handle/1874/29727

Universitat Ramon Llull

26. Puig de la Bellacasa Cazorla, Raimon. Disseny, síntesi i avaluació biològica d'inhibidors potencials de les etapes inicials del cicle de replicació del VIH.

Degree: 2010, Universitat Ramon Llull

URL: http://hdl.handle.net/10803/9300

► The human immunodeficiency virus type 1 (HIV-1) is the agent which causes acquired immunodeficiency syndrome (AIDS). A disease that was discovered in the early 80s,… (more)

▼ The human immunodeficiency virus type 1 (HIV-1) is the agent which causes acquired immunodeficiency syndrome (AIDS). A disease that was discovered in the early 80s, that nowadays affects between 31.1 and 35.8 million individuals around the world and causes 2.7 million new infections each year. For all this, and for the nearly three million deaths caused each year on average by this disease, it is considered important to try to block the virus (HIV-1), a parasite which uses the cell's metabolic machinery to replicate. Currently, the most common treatment is HAART (highly active antiretroviral therapy), which is a combination of reverse transcriptase and protease inhibitors, two viral enzymes necessary for virus replication. The main issues presented by this type of virus are the large number of mutations that can occur and, therefore, the resistance it acquires to administered drugs. It is therefore of vital importance to find new molecules which can not only replace others dealing with this problem, but can interact on new therapeutic targets. It was not until the 21st century that drugs interacting with other therapeutic targets, neither reverse transcriptase nor protease, were approved. Emphasizing Fuzeon® as an inhibitor of membrane fusion between HIV and the host cell and Selzentry® as an inhibitor of CCR5, one of the two coreceptor that the virus can use to infect the cell. However, even today there is not an approved structure to inhibit CXCR4, another entry coreceptor. Among the studied compounds against this therapeutic target highlights the AMD3100, a compound formed by two macrocycles (cyclam) linked by a p-phenylenbismethylenic spacer. During clinical trials, there was a cardiotoxic effect and a lack of oral bioavailability associated with its high positive charge at physiological pH. In the Synthesis Laboratory at IQS, a family of tetraamines analogs of AMD3100 which retain the spacer and replace the cyclam units by diamines, have been developed. These compounds showed good CXCR4 inhibitory activity. In this thesis we develop variants of these tetraamines by modification of the spacer and replacement of the cyclams by other heterocyclic systems, respectively. On the other hand, one of the first NNRTIs (Non-Nucleoside Reverse Transcriptase Inhibitors) that was discovered was 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT). In the Laboratory of Molecular Design at IQS a chemical library of analogs of this structure was selected and a synthetic route was proposed. Therefore, one objective of this work is to obtain HEPT analogs, confirm the feasibility of the proposed synthetically pathway, checking the robustness of the reactions, that the yields are high and that the reaction conditions are mild enough to automate the process. Advisors/Committee Members: Universitat Ramon Llull. IQS - Química Orgànica, [email protected] (authoremail), true (authoremailshow), Teixidó Closa, Jordi (director), Borrell Bilbao, José Ignacio (codirector).

Subjects/Keywords: HEPT; reverse transcriptase inhibitors; polyamines; CXCR4 inhibitors; HIV; HEPT; inhibidores de la transcriptasa inversa; poliaminas; inhibidores de CXCR4; VIH; HEPT; poliamines; inhibidors de la transcriptasa inversa; inhibidors de CXCR4; VIH; Química i Enginyeria Química; 547

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APA (6^th Edition):

Puig de la Bellacasa Cazorla, R. (2010). Disseny, síntesi i avaluació biològica d'inhibidors potencials de les etapes inicials del cicle de replicació del VIH. (Thesis). Universitat Ramon Llull. Retrieved from http://hdl.handle.net/10803/9300

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Puig de la Bellacasa Cazorla, Raimon. “Disseny, síntesi i avaluació biològica d'inhibidors potencials de les etapes inicials del cicle de replicació del VIH.” 2010. Thesis, Universitat Ramon Llull. Accessed March 08, 2021. http://hdl.handle.net/10803/9300.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Puig de la Bellacasa Cazorla, Raimon. “Disseny, síntesi i avaluació biològica d'inhibidors potencials de les etapes inicials del cicle de replicació del VIH.” 2010. Web. 08 Mar 2021.

Vancouver:

Puig de la Bellacasa Cazorla R. Disseny, síntesi i avaluació biològica d'inhibidors potencials de les etapes inicials del cicle de replicació del VIH. [Internet] [Thesis]. Universitat Ramon Llull; 2010. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/10803/9300.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Puig de la Bellacasa Cazorla R. Disseny, síntesi i avaluació biològica d'inhibidors potencials de les etapes inicials del cicle de replicació del VIH. [Thesis]. Universitat Ramon Llull; 2010. Available from: http://hdl.handle.net/10803/9300

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Hong Kong

27. Yeung, Yuen-ting, Yukiona. Effects of HIV protease inhibitors and non-nucleoside reverse transcriptase inbibitors on vasomotor function in rat mesentericarteries.

Degree: 2011, University of Hong Kong

URL: http://hdl.handle.net/10722/144174

Subjects/Keywords: Blood vessels - Effect of drugs on.; Protease inhibitors.; Reverse transcriptase - Inhibitors.; Rats as laboratory animals.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Yeung, Yuen-ting, Y. (2011). Effects of HIV protease inhibitors and non-nucleoside reverse transcriptase inbibitors on vasomotor function in rat mesentericarteries. (Thesis). University of Hong Kong. Retrieved from http://hdl.handle.net/10722/144174

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Yeung, Yuen-ting, Yukiona. “Effects of HIV protease inhibitors and non-nucleoside reverse transcriptase inbibitors on vasomotor function in rat mesentericarteries.” 2011. Thesis, University of Hong Kong. Accessed March 08, 2021. http://hdl.handle.net/10722/144174.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Yeung, Yuen-ting, Yukiona. “Effects of HIV protease inhibitors and non-nucleoside reverse transcriptase inbibitors on vasomotor function in rat mesentericarteries.” 2011. Web. 08 Mar 2021.

Vancouver:

Yeung, Yuen-ting Y. Effects of HIV protease inhibitors and non-nucleoside reverse transcriptase inbibitors on vasomotor function in rat mesentericarteries. [Internet] [Thesis]. University of Hong Kong; 2011. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/10722/144174.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Yeung, Yuen-ting Y. Effects of HIV protease inhibitors and non-nucleoside reverse transcriptase inbibitors on vasomotor function in rat mesentericarteries. [Thesis]. University of Hong Kong; 2011. Available from: http://hdl.handle.net/10722/144174

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Queensland University of Technology

28. Morphet, Marilynn Norma. Method for identification of effective first-line treatment for HAART naïve HIV/AIDS patients.

Degree: 2002, Queensland University of Technology

URL: http://eprints.qut.edu.au/37119/

Subjects/Keywords: Drugs Effectiveness Mathematical models; AIDS (Disease) Treatment; HIV infections Treatment; Outcome assessment (Medical care); regimen; CD4+ cell count; viral load (VL); Highly Active Anti Retroviral Therapy (HAART); treatment effect; treatment compliance; protease inhibitor; nucleoside reverse transcriptase inhibitor; non nucleoside reverse transcriptase inhibitor; thesis; masters

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Morphet, M. N. (2002). Method for identification of effective first-line treatment for HAART naïve HIV/AIDS patients. (Thesis). Queensland University of Technology. Retrieved from http://eprints.qut.edu.au/37119/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Morphet, Marilynn Norma. “Method for identification of effective first-line treatment for HAART naïve HIV/AIDS patients.” 2002. Thesis, Queensland University of Technology. Accessed March 08, 2021. http://eprints.qut.edu.au/37119/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Morphet, Marilynn Norma. “Method for identification of effective first-line treatment for HAART naïve HIV/AIDS patients.” 2002. Web. 08 Mar 2021.

Vancouver:

Morphet MN. Method for identification of effective first-line treatment for HAART naïve HIV/AIDS patients. [Internet] [Thesis]. Queensland University of Technology; 2002. [cited 2021 Mar 08]. Available from: http://eprints.qut.edu.au/37119/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Morphet MN. Method for identification of effective first-line treatment for HAART naïve HIV/AIDS patients. [Thesis]. Queensland University of Technology; 2002. Available from: http://eprints.qut.edu.au/37119/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

29. Wang, Ruibin. The impact of tenofovir disoproxil fumarate on estimated glomerular filtration rate change and progression to end-stage renal disease among HIV-infected adults in North America.

Degree: 2015, Johns Hopkins University

URL: http://jhir.library.jhu.edu/handle/1774.2/38064

► Background: Tenofovir disoproxil fumarate (TDF) was associated with an increased risk of renal toxicity, resulting in proximal tubular dysfunction, proteinuria, and chronic kidney disease (CKD).… (more)

▼ Background: Tenofovir disoproxil fumarate (TDF) was associated with an increased risk of renal toxicity, resulting in proximal tubular dysfunction, proteinuria, and chronic kidney disease (CKD). However, TDF-related nephrotoxicity has not been studied in the context of end-state renal disease (ESRD). We hypothesized that TDF-induced toxicity mainly affected a subset of susceptible HIV-infected patients that led to faster progression to ESRD. Methods: Data was extracted from 12 clinical cohorts under the North American AIDS Cohort Collaboration for Research and Design study that carried out systematic ESRD validation from January 2000 to December 2009. Piece-wise log-linear mixed effects models were used to compare and contrast estimated glomerular filtration rate (eGFR) trajectories in TDF and other nucleoside reverse transcriptase inhibitor (NRTI) therapy groups. A nested design was employed to identify risk factors associated with increased ESRD risk after TDF exposure. Results: Among the 19,653 patients, over 20% of high-risk individuals received less than two serum creatinine-based assessments of kidney function per year. For TDF users with baseline eGFR≥90, 60-89.9 and 45-59.9 mL/min/1.73m2, the annualized eGFR change decreased at -10.1% (p<-0.001), -9.9% (p<-0.001) and -27.2% (p<-0.001), respectively during the first 6 months after therapy initiation. In contrast, eGFR decreased at a slower rate or stabilized among alternative NRTI initiators during this period at rates of -5.9% (p<0.001), 0.7% (p=0.596) and 9.8% (p=0.027) for the same eGFR categories. For patients with baseline eGFR in ranges of 30-44.9 and <30 mL/min/1.73m2, eGFR change was non-significant at -14.0% (p=0.068) and -9.3% (p=0.617) per year, respectively among TDF initiators, whereas among alternative NRTI users, eGFR declined at -27.7% (p<0.001) and -31.2% (p<0.001) per year. Among TDF-exposed patients, black race was independently associated with 3.4 [95% CI: 1.2-9.6] times higher ESRD risk. Conclusion: Insufficient screening and monitoring of kidney function remains as an issue for clinical care of kidney diseases among HIV-infected patients. TDF-based therapies are associated with higher ESRD risks. TDF-induced toxicity mainly affects a small subset of susceptible individuals. Advisors/Committee Members: Abraham, Alison G (advisor).

Subjects/Keywords: HIV-infection; Tenofovir disoproxil fumarate (TDF); Nucleoside reverse transcriptase inhibitor (NRTI); End-stage renal Disease (ESRD); Glomerular filtration rate (GFR)

…nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) are excreted primarily… …disoproxil fumarate; NRTI, nucleoside reverse transcriptase inhibitor; ARV, antiretroviral drug; PI… …disease; TDF, tenofovir disoproxil fumarate; NRTI, nucleoside reverse transcriptase inhibitor… …containing TDF and a nonnucleotide reverse transcriptase inhibitor (NNRTI) in treatment… …protease inhibitors, indinavir, atazanavir and lopinavir were defined as receiving the respective…

2 more images…

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APA (6^th Edition):

Wang, R. (2015). The impact of tenofovir disoproxil fumarate on estimated glomerular filtration rate change and progression to end-stage renal disease among HIV-infected adults in North America. (Thesis). Johns Hopkins University. Retrieved from http://jhir.library.jhu.edu/handle/1774.2/38064

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wang, Ruibin. “The impact of tenofovir disoproxil fumarate on estimated glomerular filtration rate change and progression to end-stage renal disease among HIV-infected adults in North America.” 2015. Thesis, Johns Hopkins University. Accessed March 08, 2021. http://jhir.library.jhu.edu/handle/1774.2/38064.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wang, Ruibin. “The impact of tenofovir disoproxil fumarate on estimated glomerular filtration rate change and progression to end-stage renal disease among HIV-infected adults in North America.” 2015. Web. 08 Mar 2021.

Vancouver:

Wang R. The impact of tenofovir disoproxil fumarate on estimated glomerular filtration rate change and progression to end-stage renal disease among HIV-infected adults in North America. [Internet] [Thesis]. Johns Hopkins University; 2015. [cited 2021 Mar 08]. Available from: http://jhir.library.jhu.edu/handle/1774.2/38064.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wang R. The impact of tenofovir disoproxil fumarate on estimated glomerular filtration rate change and progression to end-stage renal disease among HIV-infected adults in North America. [Thesis]. Johns Hopkins University; 2015. Available from: http://jhir.library.jhu.edu/handle/1774.2/38064

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

30. Gois, Pedro Henrique França. Administração de tenofovir em ratas Wistar durante a gestação: efeitos na prole.

Degree: PhD, Nefrologia, 2014, University of São Paulo

URL: http://www.teses.usp.br/teses/disponiveis/5/5148/tde-13012015-123617/ ;

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Introdução: Tenofovir disoproxil fumarate (TDF) é um inibidor da transcriptase reversa análogo nucleotídeo que tem sido usado por gestantes para o tratamento da infecção pelo… (more)

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Introdução: Tenofovir disoproxil fumarate (TDF) é um inibidor da transcriptase reversa análogo nucleotídeo que tem sido usado por gestantes para o tratamento da infecção pelo vírus da imunodeficiência humana (HIV), bem como para a prevenção da transmissão vertical do vírus. Até o momento, não há estudos experimentais ou em humanos sobre a incidência de alterações renais nos fetos expostos a esquemas contendo TDF. Objetivo: Verificar a ocorrência de alterações renais e sistêmicas fetais causadas pelo uso do TDF durante a gestação. Metodologia: Ratos Wistar fêmeas receberam dieta padrão com ou sem adição de TDF (100mg/Kg de dieta) desde uma semana antes do cruzamento até o parto. A prole proveniente do grupo TDF foi colocada com uma mãe adotiva não tratada durante o período de amamentação e foi comparada com a prole de ratas que receberam dieta padrão durante a gestação (grupo controle). Controle e TDF foram acompanhados até três (n=9 para cada grupo) e seis (n=12 e n=10, respectivamente) meses de idade. Foram avaliados: peso corporal (PC) e pressão arterial sistólica (PAS) mensais, contagem de glomérulos, função renal (através do clearance de inulina), parâmetros bioquímicos (proteinúria, colesterol total, sódio e potássio séricos e urinários), e expressão proteica do tecido renal para componentes do sistema renina angiotensina aldosterona (SRAA) e para transportadores de sódio. Resultados: A prole TDF apresentou menor PC ao nascimento em comparação com o controle. Após o 3º mês, o grupo TDF demonstrou um crescimento compensatório, atingindo o sexto mês com maior PC. O peso renal foi menor no grupo TDF, porém, não houve diferença do número de néfrons entre os grupos. O grupo TDF apresentou alterações estruturais glomerulares. Observou-se também um aumento progressivo da PAS após o segundo mês de idade no grupo TDF. Não houve diferença estatística na função renal entre os grupos. Os níveis plasmáticos de aldosterona foram mais elevados no grupo TDF, em associação com um aumento da expressão renal do SRAA. Ratos do grupo TDF apresentaram menor excreção renal de sódio e maior expressão renal de transportadores de sódio. Conclusões: Esta é a primeira descrição, a partir de um modelo experimental, que a utilização do TDF durante a gestação resulta em hiperativação do SRAA, aumento da expressão dos transportadores renais de sódio e hipertensão arterial da prole

Introduction: Tenofovir disoproxil fumarato (TDF) is a nucleotide reverse transcriptase inhibitor that has been used in pregnants for treatment of maternal HIV infection and for prevention of vertical transmission. Currently, there are no published studies providing data regarding the occurrence of renal abnormalities in fetuses exposed to TDF-containing regimens. Objective: To evaluate the occurrence of systemic and renal abnormalities in offspring of Wistar rats exposed to TDF during pregnancy. Methods: Female Wistar rats received a standard diet, with or without addition of TDF (100 mg/Kg diet), one week before mating and during pregnancy. Offspring from the…

Advisors/Committee Members: Seguro, Antonio Carlos.

Subjects/Keywords: Acquired immunodeficiency syndrome; Drug-related side effects and adverse reactions; Efeitos colaterais e reações adversas relacionados a medicamentos; Gestação; Glomerular filtration rate/drug effects; Hepatite B; Hepatitis B; Hipertensão; HIV; HIV; Hypertension; Inibidores de transcriptase reversa/efeitos adversos; Pregnancy; Ratos Wistar; Reverse transcriptase inhibitors/adverse effects; Síndrome de imunodeficiência adquirida; Taxa de filtração Glomerular/efeitos de drogas; Tenofovir; Tenofovir; Wistar rats

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APA (6^th Edition):

Gois, P. H. F. (2014). Administração de tenofovir em ratas Wistar durante a gestação: efeitos na prole. (Doctoral Dissertation). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/5/5148/tde-13012015-123617/ ;

Chicago Manual of Style (16^th Edition):

Gois, Pedro Henrique França. “Administração de tenofovir em ratas Wistar durante a gestação: efeitos na prole.” 2014. Doctoral Dissertation, University of São Paulo. Accessed March 08, 2021. http://www.teses.usp.br/teses/disponiveis/5/5148/tde-13012015-123617/ ;.

MLA Handbook (7^th Edition):

Gois, Pedro Henrique França. “Administração de tenofovir em ratas Wistar durante a gestação: efeitos na prole.” 2014. Web. 08 Mar 2021.

Vancouver:

Gois PHF. Administração de tenofovir em ratas Wistar durante a gestação: efeitos na prole. [Internet] [Doctoral dissertation]. University of São Paulo; 2014. [cited 2021 Mar 08]. Available from: http://www.teses.usp.br/teses/disponiveis/5/5148/tde-13012015-123617/ ;.

Council of Science Editors:

Gois PHF. Administração de tenofovir em ratas Wistar durante a gestação: efeitos na prole. [Doctoral Dissertation]. University of São Paulo; 2014. Available from: http://www.teses.usp.br/teses/disponiveis/5/5148/tde-13012015-123617/ ;

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