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1.
Metabolism ; 124: 154888, 2021 11.
Article in English | MEDLINE | ID: mdl-34509494

ABSTRACT

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.


Subject(s)
Apolipoprotein A-I/metabolism , Cyclooxygenase 2/metabolism , HIV Infections/complications , Metabolic Syndrome/complications , Peptides/pharmacology , Animals , HIV Infections/metabolism , Metabolic Syndrome/metabolism , Mice
2.
Eur J Clin Microbiol Infect Dis ; 36(2): 361-371, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27848039

ABSTRACT

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.


Subject(s)
Antiviral Agents/pharmacology , Drug Resistance, Viral , Influenza A Virus, H1N1 Subtype/drug effects , Influenza A Virus, H3N2 Subtype/drug effects , Influenza, Human/virology , Aged , Female , Genotype , Greece , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Humans , Immunocompromised Host , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza A Virus, H3N2 Subtype/genetics , Influenza A Virus, H3N2 Subtype/isolation & purification , Inhibitory Concentration 50 , Male , Microbial Sensitivity Tests , Middle Aged , Mutation, Missense , Neuraminidase/genetics , Oseltamivir/pharmacology , Viral Proteins/genetics , Zanamivir/pharmacology
3.
Epidemiol Infect ; 143(14): 2950-8, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25648399

ABSTRACT

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.


Subject(s)
Influenza, Human/epidemiology , Influenza, Human/virology , Orthomyxoviridae/classification , Orthomyxoviridae/isolation & purification , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Child , Child, Preschool , Europe/epidemiology , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Young Adult
4.
Euro Surveill ; 19(16): 20782, 2014 Apr 24.
Article in English | MEDLINE | ID: mdl-24786258

ABSTRACT

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.


Subject(s)
Coronavirus Infections/diagnosis , Coronavirus/isolation & purification , Pneumonia, Viral/virology , Respiratory Tract Infections/diagnosis , Travel , Aged , Contact Tracing , Coronavirus/genetics , Coronavirus Infections/genetics , Coronavirus Infections/virology , Diarrhea , Fever/etiology , Greece , Humans , Male , Respiratory Tract Infections/virology , Reverse Transcriptase Polymerase Chain Reaction , Saudi Arabia , Syndrome , Treatment Outcome
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