[The Role of Testosterone in The Improvement of Sexual Desire in Postmenopausal Women: An Evidence-Based Clinical Review]. / O Papel da Testosterona na Melhoria do Desejo Sexual da Mulher Pós-Menopáusica: Uma Revisão Baseada na Evidência.

INTRODUCTION: Female sexual dysfunction is a common problem, affecting more than 1/3 of women during their lives. The aim of this review is to review the evidence for the effectiveness of testosterone in sexual dysfunction in postmenopausal women, particularly in the improvement of sexual desire. MATERIAL AND METHODS: The authors searched in international databases National Guidelines Clearinghouse, Guidelines Finder, Cochrane Library and MEDLINE/PubMed, for guidelines, systematic reviews, meta-analysis and randomized controlled trials, published between January 2005 and February 2017, using the MeSH terms 'testosterone', 'androgens', 'libido', 'sexual dysfunctions' and 'menopause'. RESULTS: From a pool of 506 articles, 11 were selected: three guidelines, one systematic review with meta-analysis and seven randomized controlled trials. The selected articles showed testosterone's efficacy on global sexual function and improvement of sexual desire in postmenopausal women, when both are used in monotherapy or in association with other hormones. No study showed changes in hepatic enzymes or serious adverse effects. DISCUSSION: The small sample size and short follow-up used in the included studies limits the ability to assess testosterone's long-term benefits and effects. CONCLUSION: At short-term, testosterone seems to improve sexual function in postmenopausal women, particularly sexual desire. Nevertheless, more studies with larger sample size and longer follow-up are needed to understand its long-term safety and effectiveness.

Introdução: A disfunção sexual feminina é um problema comum que atinge mais de 1/3 das mulheres em alguma fase da vida. O objetivo deste trabalho é rever a evidência existente acerca da eficácia da testosterona na disfunção sexual, em particular na melhoria do desejo, em mulheres pós-menopáusicas.Material e Métodos: Pesquisa nas bases de dados National Guidelines Clearinghouse, Guidelines Finder, The Cochrane Library e MEDLINE/PubMed, de normas de orientação clínica, revisões sistemáticas, meta-análises e ensaios clínicos aleatorizados e controlados, publicados entre janeiro de 2005 e fevereiro de 2017, utilizando os termos MeSH 'testosterone', 'androgens', 'libido', 'sexualdysfunctions' e 'menopause'.Resultados: Foram incluídos 11 artigos de uma pesquisa inicial de 506: três normas de orientação clínica, uma revisão sistemática com meta-análise e sete ensaios clínicos aleatorizados e controlados. Os artigos selecionados mostraram eficácia da terapêutica com testosterona, em monoterapia ou em associação com outras hormonas, na melhoria global da função sexual e na melhoria do desejo sexual em mulheres na pós-menopausa. Nenhum dos estudos evidenciou alterações das enzimas hepáticas ou efeitos adversos graves.Discussão: Os estudos incluídos tinham amostras de pequenas dimensões e período de follow-up curto, o que impossibilitou a avaliação dos efeitos a longo prazo do tratamento com testosterona.Conclusão: A terapêutica com testosterona tem benefício, a curto prazo, na melhoria das queixas de disfunção sexual em mulheres pós-menopáusicas, em particular na melhoria do desejo. Contudo, são necessários estudos com amostras de maior dimensão e período de follow-up mais longo, de modo a avaliar a sua efetividade e segurança a longo prazo.

Cross-protection to new drifted influenza A(H3) viruses and prevalence of protective antibodies to seasonal influenza, during 2014 in Portugal.

INTRODUCTION: Immune profile for influenza viruses is highly changeable over time. Serological studies can assess the prevalence of influenza, estimate the risk of infection, highlight asymptomatic infection rate and can also provide data on vaccine coverage. The aims of the study were to evaluate pre-existing cross-protection against influenza A(H3) drift viruses and to assess influenza immunity in the Portuguese population. MATERIALS AND METHODS: We developed a cross-sectional study based on a convenience sample of 626 sera collected during June 2014, covering all age groups, both gender and all administrative health regions of Portugal. Sera antibody titers for seasonal and new A(H3) drift influenza virus were evaluated by hemagglutination inhibition assay (HI). Seroprevalence to each seasonal influenza vaccine strain virus and to the new A(H3) drift circulating strain was estimated by age group, gender and region and compared with seasonal influenza-like illness (ILI) incidence rates before and after the study period. RESULTS: Our findings suggest that seroprevalences of influenza A(H3) (39.9%; 95% CI: 36.2-43.8) and A(H1)pdm09 (29.7%; 95% CI: 26.3-33.4) antibodies were higher than for influenza B, in line with high ILI incidence rates for A(H3) followed by A(H1)pdm09, during 2013/2014 season. Low pre-existing cross-protection against new A(H3) drift viruses were observed in A(H3) seropositive individuals (46%). Both against influenza A(H1)pdm09 and A(H3) seroprotection was highest in younger than 14-years old. Protective antibodies against influenza B were highest in those older than 65years old, especially for B/Yamagata lineage, 33.3% (95% CI: 25.7-41.9). Women showed a high seroprevalence to influenza, although without statistical significance, when compared to men. A significant decreasing trend in seroprotection from north to south regions of Portugal mainland was observed. CONCLUSIONS: Our results emphasize that low seroprotection increases the risk of influenza infection in the following winter season. Seroepidemiological studies can inform policy makers on the need for vaccination and additional preventive measures.

Effect of freezing rates and excipients on the infectivity of a live viral vaccine during lyophilization.

Lyophilization is the most popular method for achieving improved stability of labile biopharmaceuticals, but a significant fraction of product activity can be lost during processing due to stresses that occur in both the freezing and the drying stages. The effect of the freezing rate on the recovery of herpes simplex virus 2 (HSV-2) infectivity in the presence of varying concentrations of cryoprotectant excipients is reported here. The freezing conditions investigated were shelf cooling (223 K), quenching into slush nitrogen (SN2), and plunging into melting propane cooled in liquid nitrogen (LN2). The corresponding freezing rates were measured, and the ice crystal sizes formed within the samples were determined using scanning electron microscopy (SEM). The viral activity assay demonstrated the highest viral titer recovery for nitrogen cooling in the presence of low (0.25% w/v sucrose) excipient concentration. The loss of viral titer in the sample cooled by melting propane was consistently the highest among those results from the alternative cooling methods. However, this loss could be minimized by lyophilization at lower temperature and higher vacuum conditions. We suggest that this is due to a higher ratio of ice recrystallization for the sample cooled by melting propane during warming to the temperature at which freeze-drying was carried out, as smaller ice crystals readily enlarge during warming. Under the same freezing condition, a higher viral titer recovery was obtained with a formulation containing a higher concentration of sugar excipients. The reason was thought to be twofold. First, sugars stabilize membranes and proteins by hydrogen bonding to the polar residues of the biomolecules, working as a water substitute. Second, the concentrated sugar solution lowers the nucleation temperature of the water inside the virus membrane and prevents large ice crystal formation within both the virus and the external medium.

Purification of a functional gene therapy vector derived from Moloney murine leukaemia virus using membrane filtration and ceramic hydroxyapatite chromatography.

The ability of membrane ultra- and diafiltration and two chromatography media, Matrex Cellufine Sulfate (Millipore) and Macro-Prep ceramic hydroxyapatite (Bio-Rad), to adsorb, elute, and purify gene therapy vectors based on Moloney murine leukaemia virus (MoMuLV) carrying the 4070A amphotropic envelope protein was studied. Membrane ultra- and diafiltration provided virus concentration up to 160-fold with an average recovery of infectious viruses of 77 +/- 14%. In batch experiments, Macro-Prep ceramic hydroxyapatite (type 2, particle size 40 microm) proved superior to Matrex Cellufine Sulfate for MoMuLV vector particle adsorption. Furthermore, functional vector particles could be eluted using phosphate buffer pH 6.8 (highest titres from >or=300 mM phosphate) from the Macro-Prep adsorbent, with higher specific titres (cfu/mg protein) than the starting material. Similar results were obtained when this ceramic hydroxyapatite was packed into a column and used in a liquid chromatography system. Recovery of transduction-competent virus was between 18 and 31% for column experiments and 32 and 46% for batch experiments.