Twenty-six years of HIV science: an overview of anti-HIV drugs metabolism

From the identification of HIV as the agent causing AIDS, to the development of effective antiretroviral drugs, the scientific achievements in HIV research over the past twenty-six years have been formidable. Currently, there are twenty-five anti-HIV compounds which have been formally approved for clinical use in the treatment of AIDS. These compounds fall into six categories: nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), cell entry inhibitors or fusion inhibitors (FIs), co-receptor inhibitors (CRIs), and integrase inhibitors (INIs). Metabolism by the host organism is one of the most important determinants of the pharmacokinetic profile of a drug. Formation of active or toxic metabolites will also have an impact on the pharmacological and toxicological outcomes. Therefore, it is widely recognized that metabolism studies of a new chemical entity need to be addressed early in the drug discovery process. This paper describes an overview of the metabolism of currently available anti-HIV drugs.Da identificação do HIV como o agente causador da AIDS, ao desenvolvimento de fármacos antirretrovirais eficazes, os avanços científicos na pesquisa sobre o HIV nos últimos vinte e seis anos foram marcantes. Atualmente, existem vinte e cinco fármacos anti-HIV formalmente aprovados pelo FDA para utilização clínica no tratamento da AIDS. Estes compostos são divididos em seis classes: inibidores nucleosídeos de transcriptase reversa (INTR), inibidores nucleotídeos de transcriptase reversa (INtTR), inibidores não-nucleosídeos de transcriptase reversa (INNTR), inibidores de protease (IP), inibidores da entrada celular ou inibidores de fusão (IF), inibidores de co-receptores (ICR) e inibidores de integrase (INI). O metabolismo consiste em um dos maiores determinantes do perfil farmacocinético de um fármaco. A formação de metabólitos ativos ou tóxicos terá impacto nas respostas farmacológicas ou toxicológicas do fármaco. Portanto, é amplamente reconhecido que estudos do metabolismo de uma nova entidade química devem ser realizados durante as fases iniciais do processo de desenvolvimento de fármacos. Este artigo descreve uma abordagem do metabolismo dos fármacos anti-HIV atualmente disponíveis na terapêutica

Nuclear Futures Analysis and Scenario Building

This LDRD project created and used advanced analysis capabilities to postulate scenarios and identify issues, externalities, and technologies associated with future ''things nuclear''. ''Things nuclear'' include areas pertaining to nuclear weapons, nuclear materials, and nuclear energy, examined in the context of future domestic and international environments. Analysis tools development included adaptation and expansion of energy, environmental, and economics (E3) models to incorporate a robust description of the nuclear fuel cycle (both current and future technology pathways), creation of a beginning proliferation risk model (coupled to the (E3) model), and extension of traditional first strike stability models to conditions expected to exist in the future (smaller force sizes, multipolar engagement environments, inclusion of actual and latent nuclear weapons (capability)). Accomplishments include scenario development for regional and global nuclear energy, the creation of a beginning nuclear architecture designed to improve the proliferation resistance and environmental performance of the nuclear fuel cycle, and numerous results for future nuclear weapons scenarios

Reaction Channel selection techniques and γ\gamma-γ\gamma fast-timing spectroscopy using the ν\nu-Ball Spectrometer

International audienceThe reaction of a pulsed 18O beam on a self-supporting and gold-backed isotopically-enriched 164Dy target of thickness 6.3 mg/cm2 at separate primary beam energies of 71, 76 and 80 MeV was studied at the accelerator at the ALTO facility of the IPN Orsay. The γ rays produced were detected using the newly-constructed ν-Ball spectrometer which comprised of HPGe and LaBr3(Ce) detectors. This conference paper describes the methodology and effectiveness of multiplicity/sum-energy gating, for channel selection between fusion evaporation events and lower multiplicity/energy events from inelastic nuclear scattering and Coulomb excitation of the target, and from two-neutron transfer reactions to 166Dy

Half-life measurements in 164,166Dy^{164,166}\mathrm{Dy} using γ-γ{\gamma}\text{-}{\gamma} fast-timing spectroscopy with the ν{\nu}-Ball spectrometer

International audienceWe report on the measurement of lifetimes of excited states in the near-mid-shell nuclei Dy164,166 using the gamma-ray coincidence fast-timing method. The nuclei of interest were populated using reactions between an O18 beam and a gold-backed isotopically enriched Dy164 target of thickness 6.3mg/cm2 at primary beam energies of 71, 76, and 80 MeV from the IPN-Orsay laboratory, France. Excited states were populated in Dy164, Dy166, and W178,179 following Coulomb excitation, inelastic nuclear scattering, two-neutron transfer, and fusion-evaporation reaction channels respectively. Gamma rays from excited states were measured using the ν-Ball high-purity germanium (HPGe)-LaBr3 hybrid γ-ray spectrometer with the excited state lifetimes extracted using the fast-timing coincidence method using HPGe-gated LaBr3-LaBr3 triple coincident events. The lifetime of the first Iπ=2+ excited state in Dy166 was used to determine the transition quadrupole deformation of this neutron-rich nucleus for the first time. The experimental methodology was validated by showing consistency with previously determined excited state lifetimes in Dy164. The half-lives of the yrast 2+ states in Dy164 and Dy166 were 2.35(6) and 2.3(2) ns, respectively, corresponding to transition quadrupole moment values of Q0=7.58(9) and 7.5(4) eb, respectively. The lifetime of the yrast 2+ state in Dy166 is consistent with a quenching of nuclear quadrupole deformation at β≈0.35 as the N=104 mid-shell is approached

First lifetime investigations of N>82N>82 iodine isotopes: The quest for collectivity

We report on spectroscopic information and lifetime measurements in the neutron-rich I135,137,139 isotopes. This is the first lifetime data on iodine isotopes beyond N=82. Excited states were populated in fast neutron-induced fission of U238 at the ALTO facility of IJCLab with the LICORNE neutron source and detected using the hybrid ν-ball spectrometer. The level schemes of the I135,137,139 isotopes are revised in terms of excited states with up to maximum spin-parity of (33/2+), populated for the first time in fast neutron-induced fission. We provide first results on the lifetimes of the (9/21+) and (13/21+) states in I137 and I139, and the (17/21+) state in I137. In addition, we give upper lifetime limits for the (11/21+) states in I135−139, the (15/21+) state in I137, the (17/21+) state in I139, and reexamine the (29/21+) state in I137. The isomeric data in I135 are reinvestigated, such as the previously known (15/21+) and (23/21−) isomers with T1/2 of 1.64(14) and 4.6(7) ns, respectively, as obtained in this work. The new spectroscopic information is compared to that from spontaneous or thermal-neutron induced fission and discussed in the context of large scale shell-model (LSSM) calculations for the region beyond Sn132, indicating the behavior of collectivity for the three valence-proton iodine chain with N=82,84,86

Spectroscopy and lifetime measurements in 134,136,138^{134,136,138}Te isotopes and implications for the nuclear structure beyond N=82N=82

We report on spectroscopic information and lifetime measurements of even-even neutron-rich Te isotopes. Excited states were populated in fast-neutron induced fission of U238 at the ALTO facility of IJCLab with the LICORNE neutron source and detected using the hybrid ν-ball spectrometer. We provide first results on lifetimes of the 61+ state in Te136 and the (61+), (41+), and (21+) states in Te138 and discuss the results in the context of large-scale shell-model calculations. The level schemes of Te136 and Te138 are revised in terms of lifetimes of their 21+,41+ states and updated information on the (42+) state in Te136 is presented. In addition, previously reported data on spectroscopy and lifetimes in Te134 are reexamined. This work provides new insights into the evolution of collectivity for Te isotopes with N=82,84,86

The DESPEC setup for GSI and FAIR

International audienceThe DEcay SPECtroscopy (DESPEC) setup for nuclear structure investigations was developed and commissioned at GSI, Germany in preparation for a full campaign of experiments at the FRS and Super-FRS. In this paper, we report on the first employment of the setup in the hybrid configuration with the AIDA implanter coupled to the FATIMA LaBr3(Ce) fast-timing array, and high-purity germanium detectors. Initial results are shown from the first experiments carried out with the setup. An overview of the setup and function is discussed, including technical advancements along the path