7 research outputs found
CTL Escape Mediated by Proteasomal Destruction of an HIV-1 Cryptic Epitope
Cytotoxic CD8+ T cells (CTLs) play a critical role in controlling viral
infections. HIV-infected individuals develop CTL responses against epitopes
derived from viral proteins, but also against cryptic epitopes encoded by viral
alternative reading frames (ARF). We studied here the mechanisms of HIV-1 escape
from CTLs targeting one such cryptic epitope, Q9VF, encoded by an
HIVgag ARF and presented by HLA-B*07. Using PBMCs of
HIV-infected patients, we first cloned and sequenced proviral DNA encoding for
Q9VF. We identified several polymorphisms with a minority of proviruses encoding
at position 5 an aspartic acid (Q9VF/5D) and a majority encoding an asparagine
(Q9VF/5N). We compared the prevalence of each variant in PBMCs of
HLA-B*07+ and HLA-B*07- patients. Proviruses encoding Q9VF/5D were
significantly less represented in HLA-B*07+ than in HLA-B*07-
patients, suggesting that Q9FV/5D encoding viruses might be under selective
pressure in HLA-B*07+ individuals. We thus analyzed ex
vivo CTL responses directed against Q9VF/5D and Q9VF/5N. Around
16% of HLA-B*07+ patients exhibited CTL responses targeting Q9VF
epitopes. The frequency and the magnitude of CTL responses induced with Q9VF/5D
or Q9VF/5N peptides were almost equal indicating a possible cross-reactivity of
the same CTLs on the two peptides. We then dissected the cellular mechanisms
involved in the presentation of Q9VF variants. As expected, cells infected with
HIV strains encoding for Q9VF/5D were recognized by Q9VF/5D-specific CTLs. In
contrast, Q9VF/5N-encoding strains were neither recognized by Q9VF/5N- nor by
Q9VF/5D-specific CTLs. Using in vitro proteasomal digestions
and MS/MS analysis, we demonstrate that the 5N variation introduces a strong
proteasomal cleavage site within the epitope, leading to a dramatic reduction of
Q9VF epitope production. Our results strongly suggest that HIV-1 escapes CTL
surveillance by introducing mutations leading to HIV ARF-epitope destruction by
proteasomes
Dissolution Enhancement and Characterization of Nimodipine Solid Dispersions with Poloxamer 407 or PEG 6000
The solid dispersion approach is an alternative to increase drug solubility. Many carriers have been studied, but there is few information about poloxamer 407 (P407). Consequently, the objective of this study was to evaluate P407 as a carrier for nimodipine solid dispersions and to compare its solubility and dissolution rates with those from polyethylene glycol (PEG 6000). The solid dispersions were prepared by the hot melting and solvent methods and they were characterized by FTIR, DSC, solubility, and dissolution tests. The results indicated a three-fold increase in solid dispersions solubility in the presence with P407 than those prepared with PEG
<b>Desenvolvimento e Teste Preliminar da Estabilidade de formulações cosméticas acrescidas de extrato comercial de <i>Trichilia catigua</i> Adr. Juss (e) <i>Ptychopetalum olacoides</i> Bentham</b>
<p class="MsoNormal" style="margin: 0cm 0cm 0pt; line-height: normal; text-align: justify; mso-layout-grid-align: none;"> O presente estudo apresenta etapas de desenvolvimento de emulsões cosméticas, contendo 5% do extrato comercial de <i>Trichilia catigua</i> Adr. Juss (e) <i>Ptychopetalum olacoides</i> Bentham. Desenvolveramse 14 formulações-teste e avaliou-se a obtenção de emulsões macroscopicamente estáveis, com valores de viscosidade aparente variados, pH compatÃvel com o da pele e caracterÃsticas organolépticas adequadas, por meio dos Testes de Estabilidade Preliminar e Acelerada. Estas formulações foram divididas em dois grupos: um com emulsões fluidas e outro com emulsões mais viscosas. Após análise, oito formulações-teste foram consideradas aptas para serem submetidas ao Teste de Estabilidade Preliminar. Após os ensaios, cinco formulações-teste foram selecionadas para o Teste de Estabilidade Acelerada. Os ensaios foram conduzidos em condições de armazenamento, de luminosidade e de temperatura extremas. Ao final do estudo, duas formulações-teste foram consideradas aprovadas por apresentarem os perfis mais estáveis durante o estudo, sendo ambas, emulsões fluidas constituÃdas de ceras auto-emulsionantes e 0,3% p/p de um polÃmero natural, e uma delas adicionada também de 2,0% lecitina de soja. Palavras-chave: estabilidade de emulsões cosméticas; desenvolvimento de emulsões; <i>Trichilia catigua</i> Adr. Juss (e) <i>Ptychopetalum olacoides</i> Bentham</p>
FIRST-DERIVATIVE SPECTROPHOTOMETRIC DETERMINATION OF PYRIDOXINE HYDROCHLORIDE IN PHARMACEUTICAL PREPARATIONS
Prognostic Stratification of Stage IIIA pN2 Non-small Cell Lung Cancer by Hierarchical Clustering Analysis of Tissue Microarray Immunostaining Data An Alpe Adria Thoracic Oncology Multidisciplinary Group Study (ATOM 014)
Prognostic stratification of stage IIIA pN2 non-small cell lung cancer by hierarchical clustering analysis of tissue microarray immunostaining data: an Alpe Adria Thoracic Oncology Multidisciplinary Group study (ATOM 014)
Physical and physicochemical stability evaluation of cosmetic formulations containing soybean extract fermented by Bifidobacterium animalis
Peel off facial masks, based on polyvinyl alcohol (PVA), are formulations that, after application and drying, form an occlusive film over the face. After removing, they provide cleanness, tensor and moisturizing effects, removing dead cells, residues and other materials deposited on the stratum corneous. The soybean extract fermented by Bifidobacterium animalis has sugars, amino acids, peptides, proteins and free isoflavonoids in high concentrations, when compared to the unfermented extract, providing benefits to the cosmetic formulations like anti-aging effect, moisture, tensor action and emollience. The cosmetic bases of peel off facial masks, added with 5.0% w/w of fermented soybean extract, were submitted to Preliminary and Accelerated Stability Studies. Eight (8) preparations were evaluated in several conditions of temperature (-10.0, 5.0, 22.0 and 45.0 ºC) and time (maximum of 15 days), comparing the results with the initial condition (48 h after preparation). The variables observed were: organoleptic characteristics, pH and appearing viscosity value and film drying time. The preparation containing 17.0% w/w of PVA and 0.5% w/w of guar gum was selected between the eight preparations initially prepared, because it presented the best performance in the stability test, being recommended storage at low temperatures (5.0 ºC).<br>As máscaras faciais peel off a base de álcool polivinÃlico (PVA) são formulações que, após a aplicação e secagem, formam um filme oclusivo sobre a face e, após sua remoção, conferem limpeza, ação tensora e hidratação à pele, retirando células mortas do estrato córneo, resÃduos e outros materiais depositados. O extrato de soja fermentado por Bifidobacterium animalis possui açúcares, aminoácidos, peptÃdeos, e alto teor de isoflavonas na forma livre, quando comparado ao leite não fermentado, propiciando benefÃcios à s formulações cosméticas, como ação antienvelhecimento, hidratação, efeito tensor e emoliência. As bases cosméticas de máscaras faciais peel off, acrescidas de extrato de soja fermentado 5,0% p/p, foram submetidas aos ensaios de Estabilidade Preliminar e Acelerada, avaliando-se 8 preparações em diversas condições de temperatura (-10,0; 5,0; 22,0 e 45,0 ºC) e tempo (máximo de 15 dias), em relação à condição inicial (48 h após o preparo). As variáveis observadas envolveram: caracterÃsticas organolépticas, valor de pH, viscosidade aparente e tempo de secagem do filme. A preparação contendo 17,0% p/p de PVA e 0,5% p/p de goma guar foi a selecionada dentre as oito preparações elaboradas inicialmente, por ter apresentado melhor desempenho no teste de estabilidade, sendo recomendado o armazenamento em temperatura reduzida (5,0 ºC)