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1.
Metabolism ; 124: 154888, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34509494

RESUMO

OBJECTIVE: We investigated whether apolipoprotein A-I (apoA-I) mimetic peptides 4F and 6F can be a novel therapeutic strategy to reduce blood and gut bioactive lipids, proinflammatory effects of endotoxin (LPS) and aberrant activation of cyclooxygenase 2 (COX-2) as instigators of increased risk for cardiometabolic disease in chronic treated HIV. METHODS: We used two humanized murine models of chronic treated HIV infection (n = 109 mice) and gut explants from HIV infected (n = 10) persons to determine whether Tg6F and 4F attenuate in vivo and ex vivo increased blood and gut bioactive lipids (measured by mass spectrometry) and intestinal protein levels of COX-2 (measured by immunoassays) in chronic treated HIV. RESULTS: In these models of HIV, when compared to HIV-1 infected mice on antiretroviral therapy (ART) alone, oral Tg6F in combination with ART attenuated increases in plasma and gut bioactive lipids (and particularly COX lipids) and intestinal COX-2. 4F and Tg6F also reduced ex vivo production of COX-2 protein and associated secretion of bioactive lipids in gut explants from HIV-1 infected persons treated with LPS. CONCLUSION: ApoA-I mimetics favorably impact the proinflammatory effects of LPS, COX-2 and production of bioactive lipids that collectively drive gut and systemic inflammation in chronic treated HIV. Given prior experimental evidence that the proinflammatory effects of LPS, COX-2 and gut dysfunction contribute to cardiometabolic syndrome in chronic HIV, apoA-I mimetic peptides may be a novel therapy to treat cardiometabolic syndrome in chronic HIV.


Assuntos
Apolipoproteína A-I/metabolismo , Ciclo-Oxigenase 2/metabolismo , Infecções por HIV/complicações , Síndrome Metabólica/complicações , Peptídeos/farmacologia , Animais , Infecções por HIV/metabolismo , Síndrome Metabólica/metabolismo , Camundongos
2.
Eur J Clin Microbiol Infect Dis ; 36(2): 361-371, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27848039

RESUMO

There was an increase in severe and fatal influenza cases in Greece during the 2011-2015 post-pandemic period. To investigate causality, we determined neuraminidase (NA) inhibitor susceptibility and resistance-conferring NA and hemagglutinin (HA) mutations in circulating influenza type A viruses during the pandemic (2009-2010) and post-pandemic periods in Greece. One hundred thirty-four influenza A(H1N1)pdm09 and 95 influenza A(H3N2) viruses submitted to the National Influenza Reference Laboratory of Southern Greece were tested for susceptibility to oseltamivir and zanamivir. Antiviral resistance was assessed by neuraminidase sequence analysis, as well as the fluorescence-based 50 % inhibitory concentration (IC50) method. Five influenza A(H1N1)pdm09 viruses (2.2 %) showed significantly reduced inhibition by oseltamivir (average IC50 300.60nM vs. 1.19nM) by Gaussian kernel density plot analysis. These viruses were isolated from immunocompromised patients and harbored the H275Y oseltamivir resistance-conferring NA substitution. All A(H1N1)pdm09 viruses were zanamivir-susceptible, and all A(H3N2) viruses were susceptible to both drugs. Oseltamivir-resistant viruses did not form a distinct cluster by phylogenetic analysis. Permissive mutations were detected in immunogenic and non immunogenic NA regions of both oseltamivir- resistant and susceptible viruses in the post-pandemic seasons. Several amino acid substitutions in the HA1 domain of the HA gene of post-pandemic viruses were identified. This study indicated low resistance to NAIs among tested influenza viruses. Antiviral resistance emerged only in immunocompromised patients under long-term oseltamivir treatment. Sequential sample testing in this vulnerable group of patients is recommended to characterise resistance or reinfection and viral evolution.


Assuntos
Antivirais/farmacologia , Farmacorresistência Viral , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Influenza Humana/virologia , Idoso , Feminino , Genótipo , Grécia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Humanos , Hospedeiro Imunocomprometido , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Concentração Inibidora 50 , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Neuraminidase/genética , Oseltamivir/farmacologia , Proteínas Virais/genética , Zanamivir/farmacologia
3.
Epidemiol Infect ; 143(14): 2950-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25648399

RESUMO

The epidemiology of seasonal influenza is influenced by age. During the influenza season, the European Influenza Surveillance Network (EISN) reports weekly virological and syndromic surveillance data [mostly influenza-like illness (ILI)] based on national networks of sentinel primary-care providers. Aggregated numbers by age group are available for ILI, but not linked to the virological data. At the end of the influenza season 2012/2013, all EISN laboratories were invited to submit a subset of their virological data for this season, including information on age. The analysis by age group suggests that the overall distribution of circulating (sub)types may mask substantial differences between age groups. Thus, in cases aged 5-14 years, 75% tested positive for influenza B virus whereas all other age groups had an even distribution of influenza A and B viruses. This means that the intepretation of syndromic surveillance data without age group-specific virological data may be misleading. Surveillance at the European level would benefit from the reporting of age-specific influenza data.


Assuntos
Influenza Humana/epidemiologia , Influenza Humana/virologia , Orthomyxoviridae/classificação , Orthomyxoviridae/isolamento & purificação , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Europa (Continente)/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Euro Surveill ; 19(16): 20782, 2014 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-24786258

RESUMO

On 18 April 2014, a case of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection was laboratory confirmed in Athens, Greece in a patient returning from Jeddah, Saudi Arabia. Main symptoms upon initial presentation were protracted fever and diarrhoea, during hospitalisation he developed bilateral pneumonia and his condition worsened. During 14 days prior to onset of illness, he had extensive contact with the healthcare environment in Jeddah. Contact tracing revealed 73 contacts, no secondary cases had occurred by 22 April.


Assuntos
Infecções por Coronavirus/diagnóstico , Coronavirus/isolamento & purificação , Pneumonia Viral/virologia , Infecções Respiratórias/diagnóstico , Viagem , Idoso , Busca de Comunicante , Coronavirus/genética , Infecções por Coronavirus/genética , Infecções por Coronavirus/virologia , Diarreia , Febre/etiologia , Grécia , Humanos , Masculino , Infecções Respiratórias/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Arábia Saudita , Síndrome , Resultado do Tratamento
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