RESUMO
We studied the presence of primary resistance to raltegravir (RAL), natural polymorphisms, and selection pressure on HIV-1 integrase. We found a high frequency of integrase polymorphisms related to the resistance to RAL and sequence stability. Further studies are needed to determine the importance of these polymorphisms to RAL resistance.
Assuntos
Fármacos Anti-HIV/farmacologia , Terapia Antirretroviral de Alta Atividade/métodos , Farmacorresistência Viral , Infecções por HIV/transmissão , HIV-1/efeitos dos fármacos , Pirrolidinonas/farmacologia , Seleção Genética , Sequência de Aminoácidos , Brasil/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Integrase de HIV/genética , HIV-1/isolamento & purificação , Humanos , Masculino , Dados de Sequência Molecular , Filogenia , Polimorfismo Genético , Raltegravir Potássico , Homologia de Sequência de Aminoácidos , Falha de TratamentoRESUMO
To experience sexual violence and abuse is to experience silence. This commentary explores some of the ways in which psychiatry reinforces the silencing of sexual violence survivors. We argue that current psychiatric responses to sexual violence typically constitute iatrogenic harm including through: a failure to provide services that meet survivors' needs, a failure to believe or validate disclosures; experiences of medicalisation and diagnoses which can delegitimise people's own knowledge and meaning; 'power over' relational approaches which can prevent compassionate responses and result in staff having to develop their own coping strategies; and poorly addressed and reported experiences of sexual violence within psychiatric settings. We argue that these multiple forms of silencing have arisen in part because of biomedical dominance, a lack of support and training in sexual violence for staff, inconsistent access to structured, reflective supervision, and the difficulties of facing the horror of sexual violence and abuse. We then describe community-based and grassroots responses, and consider the potential of trauma-informed approaches. Whilst this paper has a UK focus, some aspects will resonate globally, particularly given that Western psychiatry is increasingly being exported around the globe.
Assuntos
Serviços de Saúde Mental , Estupro/psicologia , Delitos Sexuais/psicologia , Pesquisa sobre Serviços de Saúde , HumanosAssuntos
Neoplasias dos Ductos Biliares/diagnóstico por imagem , Ductos Biliares Extra-Hepáticos/diagnóstico por imagem , Colangiocarcinoma/diagnóstico por imagem , Endossonografia/métodos , Situs Inversus/diagnóstico por imagem , Idoso , Neoplasias dos Ductos Biliares/complicações , Colangiocarcinoma/complicações , Diagnóstico Diferencial , Humanos , Masculino , Situs Inversus/complicaçõesRESUMO
The platinum mixed-phosphine complexes (SP-4,2)-[PtCl(8-MTT)(PPh3)(PTA)] (2) and cis-[Pt(8-MTT)2(PPh3)(PTA)] (3) (MTTH2 = 8-(methylthio)theophylline, PTA = 1,3,5-triaza-7-phosphaadamantane) have been prepared from the precursor cis-[PtCl2(PPh3)(PTA)] (1), which has been fully characterized by X-ray diffraction determination. Antiproliferative activity tests indicated that the presence of one lipophilic PPh3 and one hydrophilic PTA makes 1-3 more active than the analogues bearing two PPh3 or two PTA. The reactivity of cis-[PtCl2(PPh3)2], cis-[PtCl2(PTA)2], and cis-[PtCl2(PPh3)(PTA)] with the bis(thiopurines) bis(S-8-thiotheophylline)methane (MBTTH2), 1,2-bis(S-8-thiotheophylline)ethane (EBTTH2), and 1,3-bis(S-8-thiotheophylline)propane (PBTTH2) has also been investigated. New binuclear complexes have been prepared and identified by spectroscopic techniques and their antiproliferative activities on T2 and SKOV3 cell lines evaluated.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Ácidos Fosfínicos/química , Ácidos Fosfínicos/farmacologia , Compostos de Platina/síntese química , Compostos de Platina/farmacologia , Teofilina/análogos & derivados , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indicadores e Reagentes , Ligantes , Metais/química , Modelos Moleculares , Purinas/química , Teofilina/síntese química , Teofilina/farmacologiaRESUMO
Complexes [Pt(mu-N,S-8-TT)(PPh(3))(2)](2) (1), [Pt(mu-S,N-8-TT)(PTA)(2)](2) (2), [Pt(8-TTH)(terpy)]BF(4) (3), cis-[PtCl(8-MTT)(PPh(3))(2)] (4), cis-[Pt(8-MTT)(2)(PPh(3))(2)] (5), cis-[Pt(8-MTT)(8-TTH)(PPh(3))(2)] (6), cis-[PtCl(8-MTT)(PTA)(2)] (7), cis-[Pt(8-MTT)(2)(PTA)(2)] (8), and trans-[Pt(8-MTT)(2)(py)(2)] (9) (8-TTH(2) = 8-thiotheophylline; 8-MTTH = 8-(methylthio)theophylline; PTA = 1,3,5-triaza-7-phosphaadamantane) are presented and studied by IR and multinuclear ((1)H, (31)P[(1)H]) NMR spectroscopy. The solid-state structure of 4 and 9 has been authenticated by X-ray crystallography. Growth inhibition of the cancer cells T2 and SKOV3 induced by the above new thiopurine platinum complexes has been investigated. The activity shown by complexes 4 and 9 was comparable with cisplatin on T2. Remarkably, 4 and 9 displayed also a valuable activity on cisplatin-resistant SKOV3 cancer cells.