Efficacy of fewer than three doses of an HPV-16/18 AS04-adjuvanted vaccine: combined analysis of data from the Costa Rica Vaccine and PATRICIA Trials.

BACKGROUND: There is some evidence to suggest that one or two doses of the HPV vaccine provides similar protection to the three-dose regimen. The main aim of the study was to ascertain HPV-16/18 vaccine efficacy in both full and naive cohorts and to explore protection conferred against non-vaccine HPV types, by number of doses received. METHODS: Summary data from the Costa Rica Vaccine Trial (CVT; NCT00128661) and ~the PATRICIA trial (NCT001226810), two phase 3, double-blind, randomised controlled clinical trials of the HPV-16/18 AS04-adjuvanted vaccine in young women, were combined in a post-hoc analysis (GlaxoSmithKline [GSK] e-track number 202142) to investigate the efficacy of fewer than three doses of the HPV-16/18 vaccine after 4 years of follow-up. Women were randomly assigned to receive three doses of the HPV-16/18 vaccine or to a control vaccine; yet, some received fewer doses. After exclusion of women with less than 12 months of follow-up or those who were HPV-16/18 DNA-positive at enrolment (for the HPV-16/18 endpoint), we calculated vaccine efficacy against one-time detection of incident HPV infections after three, two, and one dose(s). The primary study endpoint was one-time detection of first incident HPV-16/18 infections accumulated during the follow-up phase. FINDINGS: We assessed vaccine efficacy against incident HPV-16/18 infection in the modified total vaccinated cohort (22 327 received three doses, 1185 two doses, 543 one dose). Vaccine efficacy against incident HPV-16/18 infections for three doses was 77·0% (95% CI 74·7-79·1), two doses was 76·0% (62·0-85·3), and one dose was 85·7% (70·7-93·7). Vaccine efficacy against incident HPV-31/33/45 infections for three doses was 59·7% (56·0-63·0), two doses was 37·7% (12·4-55·9), and one dose was 36·6% (-5·4 to 62·2). Vaccine efficacy against incident HPV-16/18 infection for two-dose women who received their second dose at 1 month was 75·3% (54·2-87·5) and 82·6% (42·3-96·1) for those who received the second dose at 6 months (CVT data only). Vaccine efficacy against HPV-31/33/45 for two-dose women who received their second dose at 6 months (68·1%, 27·0-87·0; CVT data only), but not those receiving it at one month (10·1%, -42·0 to 43·3), was similar to the three-dose group. INTERPRETATION: 4 years after vaccination of women aged 15-25 years, one and two doses of the HPV-16/18 vaccine seem to protect against cervical HPV-16/18 infections, similar to the protection provided by the three-dose schedule. Two doses separated by 6 months additionally provided some cross-protection. These data argue for a direct assessment of one-dose efficacy of the HPV-16/18 vaccine. FUNDING: US National Cancer Institute, National Institutes of Health Office of Research on Women's Health, and Ministry of Health of Costa Rica (CVT); GlaxoSmithKline Biologicals SA (PATRICIA).

Haemonchus contortus protease inhibition by n-alkyl ferulates from Maprounea guianensis.

This report describes the inhibition of the proteolytic activity of Haemonchus contortus lysate by a mixture of n-alkyl ferulates isolated from Maprounea guianensis. These compounds were evaluated in vitro for the ability to inhibit the H. contortus proteases using SDS-PAGE copolymerized with gelatine (zymography) and by assaying the hemoglobinolytic activity of these enzymes in solution. The ferulates abrogated the proteolysis compared to E-64, suggesting the activity is the result of a cysteine protease.

Box-Behnken design: an alternative for the optimization of analytical methods.

The present paper describes fundamentals, advantages and limitations of the Box-Behnken design (BBD) for the optimization of analytical methods. It establishes also a comparison between this design and composite central, three-level full factorial and Doehlert designs. A detailed study on factors and responses involved during the optimization of analytical systems is also presented. Functions developed for calculation of multiple responses are discussed, including the desirability function, which was proposed by Derringer and Suich in 1980. Concept and evaluation of robustness of analytical methods are also discussed. Finally, descriptions of applications of this technique for optimization of analytical methods are presented.

Atividade antibacteriana em alguns extratos de vegetais do semi-árido brasileiro

Espécies nativas ou endêmicas do semi-árido brasileiro foram investigadas com o intuito de se descobrir novas drogas antimicrobianas. Os ensaios foram realizados contra cepas padrões de Staphylococcus aureus e Escherichia coli através do método de difusão em disco. Dos 137 extratos de vegetais avaliados, sete apresentaram atividade significativa contra o Staphylococcus aureus. Os extratos ativos foram preparados a partir de espécies pertencentes às famílias Leguminosae e Rutaceae e serão futuramente fracionados com o intuito de se chegar às moléculas ativas.

Species native or endemic of the Brazilian semi-arid were investigated with the intention of discovering new antibacterial drugs. The rehearsals were accomplished against standard strains of Staphylococcus aureus and Escherichia coli through the diffusion method in disk. Of the 137 extracts of appraised vegetables, seven presented significant activity against the Staphylococcus aureus. The active extracts were prepared starting from species belonging to the Leguminosae and Rutaceae families and they will be fractional hereafter with the intention of arriving to the active molecules.

Atividade antioxidante de substâncias presentes em Dioclea violacea e Erythroxylum nummularia

This work describes the evaluation of the antioxidant activity in the system b-carotene / linoleic acid and radical scavenging effects of the substances 2',4'-dihydroxychalcone, 2',3,4,4'-tetrahydroxychalcone (butein), 4-methoxy-2',3,4'-trihydroxychalcone, 7-hydroxyflavanone, 3',4',7-trihydroxyflavanone (butin), 7,4'-dihydroxyflavanone (liquiritigenin), 6-methoxy-7- hydroxydihydroflavonol and lasiodiplodin isolated of the extract CHCl3 of the stem of Dioclea violacea and 3',4',5,7-tetrahydroxyflavanol (quercetin), 4',7- dimethoxy-3',5-dihydroxyflavanol and epicatechin isolated of the Erythroxylum nummularia leaves. These compounds were evaluated and compared with the antioxidant standards n-propyl gallate, BHT and á α-tocoferol.

Biflavonoids from Ouratea multiflora.

A new flavone dimer, 3-hydroxy-4',5,7-trimethoxyflavone-(6-->8")-3"-hydroxy-3"',4"', 5",7"-tetramethoxyflavone, together with amenthoflavone, have been isolated from the leaves of Ouratea multiflora. Its structure was established by spectroscopic methods, including two-dimensional NMR spectroscopy.

Constituents of Caesalpinia pyramidalis.

Two new glycosyl phenylpropenoid acids, 4-O-beta-glucopyranosyloxy-(Z)-7-hydroxycinnamic acid (1) and 4-O-beta-glucopyranosyloxy-(Z)-8-hydroxycinnamic acid (2), besides lupeol and aghatisflavone, were isolated from the leaves of Caesalpinia pyramidalis.

A-type proanthocyanidin antioxidant from Dioclea lasiophylla.

The A-type proanthocyanidin, epigallocatechin-(2beta-->7,4beta-->8)-epicatechin, together with the known epicatechin, luteolin 3'beta-D-glucopyranoside, chrysoeriol 7beta-D-glucopyranoside and 2-methylpentan-2,4-diol, were isolated from leaves of Dioclea lasiophilla. The structures were established on the basis of their spectral data. Antioxidant activities of isolates were measured using the autooxidation of beta-carotene in a linolenic acid suspension method.