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The Sicilian sumac (Rhus coriaria L.) is considered an excellent source of natural polyphenols whose antioxidant activity is able to affect specific technological functions. The effect of the Rhus coriaria addition on the quality of beef burgers before and after cooking was evaluated, by pH, colour, protein (-SH) and lipid oxidation, total phenol content and antioxidant activity (ABTS assay). The sumac in burgers (THs) resulted in a significant increase in all dry matter components (P < 0.05), while water content and pH value decreased. Furthermore, THs, compared with control burgers (CHs), were characterised by lower L* and peroxidation values and higher a* and b* values (p < 0.05). The Rhus added in the burgers positively influenced the total phenolic content and antioxidant activity values. Cooking reduced content of phenols, -SH groups and antioxidant activity. However, in THs the reduction of -SH, phenols and antioxidant activity was more limited than in CHs (p < 0.05). Sensory analysis showed a higher appreciation for THs by consumers for all the considered attributes. The ground meat incorporated with sumac could be a valid strategy to improve its quality and sensorial evaluation.
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The aim of the present work was to evaluate and compare in vitro the antioxidant activity of raw, cooked and cooked-digested pork, beef and chicken burgers. The cooking process influenced the antioxidant capacity of the meat by decreasing the values of ABTS, FRAP and the content of free thiols. Conversely, a positive effect was observed after in vitro gastrointestinal digestion which increased the biological activity of the meat, characterised by greater antioxidant activity. The type of meat influenced the chemical composition and biological capacity of the burgers. In fact, both before and after the cooking process, beef burgers showed higher thiol content and, consequently, a higher oxidative stability of proteins than chicken and pork burgers. In vitro gastrointestinal digestion also improved the nutraceutical quality of beef burgers, which showed higher ABTS values and thiol content than pork burgers, which showed higher FRAP values. This work aims to support the potential of meat constituents as a natural antioxidant component that is essential to counteract the oxidative stress responsible for imbalances in the human organism and several cardiovascular diseases.
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This study investigated the chemical and functional characterization of propolis collected in southern Italy, in particular in Basilicata, a region rich in ecological and vegetative biodiversity. Sixteen samples of propolis, collected within a radius of 40 km from each other in the Basilicata region, showed significant differences between the chemical and functional parameters investigated: color index (L*, a*, b*; p < 0.05) and variation in chemical composition and antioxidant activities by ABTS and FRAP assays. In general, Lucanian propolis had a low content of waxes (p < 0.05) and a high content of resin (p < 0.05) and balsams (p < 0.05). The content of the total phenolic compounds and flavonoids was highly variable, as was the biological capacity. In conclusion, Lucanian propolis showed remarkable variability, highlighting significant diversification according to the geographical position and the diversity of the flora surrounding the apiary that the bees use as a source of resin. This study, therefore, contributes to the enhancement of the quality of propolis, laying the foundations for the production and marketing of propolis not only in the food industry but also in the pharmaceutical and cosmetic industries.
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Prostaglandins (PGs) are hormone-like mediators in many physiological and pathological processes that are present in all vertebrates, in some terrestrial and aquatic invertebrates, and have also been identified in some macroalgae. They have recently been reported also in marine microalgae but their role as chemical mediators is largely unknown. Here we studied the expression pattern of the PG biosynthetic pathway during different growth phases of the centric diatom Thalassiosira rotula and assessed the release of PGs in the surrounding environment for the first time. We show that enzymes responsible for PGs formation such as cyclooxygenase, prostaglandin E synthase 2-like and prostaglandin F synthase are mainly expressed at the end of the exponential phase and that PGs are released especially during the stationary and senescent phases, suggesting a possible signaling function for these compounds. Phylogenetic analysis of the limiting enzyme, COX, indicate the presence in diatoms of more than one enzyme related to the oxidative metabolism of fatty acids belonging to the peroxidase-cyclooxygenase superfamily. These findings suggest a more complex evolution and diversity of metabolic pathways leading to the synthesis of lipid mediators in diatoms.
Assuntos
Diatomáceas/crescimento & desenvolvimento , Diatomáceas/metabolismo , Prostaglandinas/metabolismo , Fenômenos Biológicos , Vias Biossintéticas , Ciclo-Oxigenase 2/metabolismo , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação Bacteriana da Expressão Gênica/genética , Metabolismo dos Lipídeos , Microalgas/metabolismo , Filogenia , Transdução de Sinais , Transcriptoma/genéticaRESUMO
Diatoms are phytoplankton eukaryotic microalgae that are widely distributed in the world's oceans and are responsible for 20-25% of total carbon fixation on the planet. Using transcriptome sequencing here we show for the first time that the ubiquitous diatom Thalassiosira rotula expresses biosynthetic pathways that potentially lead to the synthesis of interesting secondary metabolites with pharmaceutical applications such as polyketides, prostaglandins and secologanin. We also show that these pathways are differentially expressed in conditions of silica depletion in comparison with standard growth conditions.
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Vias Biossintéticas/genética , Diatomáceas/genética , Diatomáceas/metabolismo , Glucosídeos Iridoides/metabolismo , Policetídeos/metabolismo , Prostaglandinas/metabolismo , Transcriptoma , Diatomáceas/crescimento & desenvolvimentoRESUMO
Brassica phytochemicals exert a broad spectrum of health-promoting activities. The aim of this study was to investigate the possible beneficial effects of a cauliflower leaf powder (CLP)-enriched diet to prevent inflammation and oxidative stress resulting from injection of lipopolysaccharide (LPS) into rabbits. Animals (24 rabbits) were randomly divided into two groups and fed with a standard diet (SD) or a standard diet supplemented with a 100 g kg-1 diet of CLP. After 60 days, six rabbits of both groups received a LPS injection (100 µg per kg body weight). Serum samples collected after 90 min of LPS injection were assessed for their content of both inflammatory biomarkers such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and matrix-metalloproteinases (MMP-2 and MMP-9) and oxidative stress biomarkers such as thiobarbituric acid reactive substances (TBARS), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). LPS increased the levels of TNF-α, IL-6, and TBARS as well as MMP-2 and MMP-9 activities, whereas it decreased the GSH levels and SOD and CAT activities. In conclusion, preventive supplementation with CLP can protect rabbits from the inflammation and oxidative stress induced by LPS.
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Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Brassica/metabolismo , Inflamação/dietoterapia , Folhas de Planta/metabolismo , Preparações de Plantas/metabolismo , Animais , Brassica/química , Catalase/genética , Catalase/metabolismo , Glutationa/metabolismo , Humanos , Inflamação/genética , Inflamação/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos/efeitos adversos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Folhas de Planta/química , Preparações de Plantas/química , Coelhos , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The cell adhesion protein and tumour suppressor E-cadherin exhibits important functions in the prevention of gastric cancer. As a class-I carcinogen, Helicobacter pylori (H. pylori) has developed a unique strategy to interfere with E-cadherin functions. In previous studies, we have demonstrated that H. pylori secretes the protease high temperature requirement A (HtrA) which cleaves off the E-cadherin ectodomain (NTF) on epithelial cells. This opens cell-to-cell junctions, allowing bacterial transmigration across the polarised epithelium. Here, we investigated the molecular mechanism of the HtrA-E-cadherin interaction and identified E-cadherin cleavage sites for HtrA. Mass-spectrometry-based proteomics and Edman degradation revealed three signature motifs containing the [VITA]-[VITA]-x-x-D-[DN] sequence pattern, which were preferentially cleaved by HtrA. Based on these sites, we developed a substrate-derived peptide inhibitor that selectively bound and inhibited HtrA, thereby blocking transmigration of H. pylori. The discovery of HtrA-targeted signature sites might further explain why we detected a stable 90 kDa NTF fragment during H. pylori infection, but also additional E-cadherin fragments ranging from 105 kDa to 48 kDa in in vitro cleavage experiments. In conclusion, HtrA targets E-cadherin signature sites that are accessible in in vitro reactions, but might be partially masked on epithelial cells through functional homophilic E-cadherin interactions.
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Proteínas de Bactérias/metabolismo , Caderinas/metabolismo , Helicobacter pylori/enzimologia , Serina Proteases/metabolismo , Motivos de Aminoácidos , Antígenos CD , Proteínas de Bactérias/antagonistas & inibidores , Caderinas/química , Caderinas/genética , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Humanos , Dados de Sequência Molecular , Peptídeos/análise , Peptídeos/síntese química , Peptídeos/metabolismo , Ligação Proteica , Proteólise , Proteômica , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Serina Proteases/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Especificidade por Substrato , Ressonância de Plasmônio de SuperfícieRESUMO
Sustained identification of innovative chemical entities is key for the success of chemical biology and drug discovery. We report the fragment-based, computer-assisted deâ novo design of a small molecule inhibiting Helicobacter pylori HtrA protease. Molecular binding of the designed compound to HtrA was confirmed through biophysical methods, supporting its functional activity in vitro. Hit expansion led to the identification of the currently best-in-class HtrA inhibitor. The results obtained reinforce the validity of ligand-based deâ novo design and binding-kinetics-guided optimization for the efficient discovery of pioneering lead structures and prototyping drug-like chemical probes with tailored bioactivity.
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Proteínas de Bactérias/antagonistas & inibidores , Desenho de Fármacos , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Peptídeo Hidrolases/química , Inibidores de Proteases/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Desenho Assistido por Computador , Descoberta de Drogas , Infecções por Helicobacter/microbiologia , Helicobacter pylori/enzimologia , Humanos , Ligantes , Relação Estrutura-AtividadeRESUMO
Natural products have long been a source of useful biological activity for the development of new drugs. Their macromolecular targets are, however, largely unknown, which hampers rational drug design and optimization. Here we present the development and experimental validation of a computational method for the discovery of such targets. The technique does not require three-dimensional target models and may be applied to structurally complex natural products. The algorithm dissects the natural products into fragments and infers potential pharmacological targets by comparing the fragments to synthetic reference drugs with known targets. We demonstrate that this approach results in confident predictions. In a prospective validation, we show that fragments of the potent antitumour agent archazolid A, a macrolide from the myxobacterium Archangium gephyra, contain relevant information regarding its polypharmacology. Biochemical and biophysical evaluation confirmed the predictions. The results obtained corroborate the practical applicability of the computational approach to natural product 'de-orphaning'.
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Produtos Biológicos/química , Descoberta de Drogas/métodos , Substâncias Macromoleculares/química , Ácido Araquidônico/química , Desenho de Fármacos , Macrolídeos/química , Estrutura Molecular , Receptores Citoplasmáticos e Nucleares/fisiologia , Tiazóis/química , ATPases Vacuolares Próton-Translocadoras/antagonistas & inibidoresRESUMO
BACKGROUND: Prioritizing building blocks for combinatorial medicinal chemistry represents an optimization task. We present the application of an artificial ant colony algorithm to combinatorial molecular design (Molecular Ant Algorithm [MAntA]). RESULTS: In a retrospective evaluation, the ant algorithm performed favorably compared with other stochastic optimization methods. Application of MAntA to peptide design resulted in new octapeptides exhibiting substantial binding to mouse MHC-I (H-2K(b)). In a second study, MAntA generated a new functional factor Xa inhibitor by Ugi-type three-component reaction. CONCLUSION: This proof-of-concept study validates artificial ant systems as innovative computational tools for efficient building block prioritization in combinatorial chemistry. Focused activity-enriched compound collections are obtained without the need for exhaustive product enumeration.
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Algoritmos , Técnicas de Química Combinatória/métodos , Desenho de Fármacos , Peptídeos/química , Peptídeos/farmacologia , Sequência de Aminoácidos , Animais , Inibidores do Fator Xa , Antígenos H-2/metabolismo , Humanos , Camundongos , Dados de Sequência MolecularRESUMO
Helicobacter pylori is associated with inflammatory diseases and can cause gastric cancer and mucosa-associated lymphoma. One of the bacterium's key proteins is high temperature requirement A (HpHtrA) protein, an extracellular serine protease that cleaves E-cadherin of gastric epithelial cells, which leads to loss of cell-cell adhesion. Inhibition of HpHtrA may constitute an intervention strategy against H. pylori infection. Guided by the computational prediction of hypothetical ligand binding sites on the surface of HpHtrA, we performed residue mutation experiments that confirmed the functional relevance of an allosteric region. We virtually screened for potential ligands addressing this surface cleft located between the catalytic and PDZ1 domains. Our receptor-based computational method represents protein surface pockets in terms of graph frameworks and retrieves small molecules that satisfy the constraints given by the pocket framework. A new chemical entity was identified that blocked E-cadherin cleavage in vitro by direct binding to HpHtrA, and efficiently blocked pathogen transmigration across the gastric epithelial barrier. A preliminary crystal structure of HpHtrA confirms the validity of a comparative "homology" model of the enzyme, which we used for the computational study. The results of this study demonstrate that addressing orphan protein surface cavities of target macromolecules can lead to new bioactive ligands.
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Designed peptides that bind to major histocompatibility protein I (MHC-I) allomorphs bear the promise of representing epitopes that stimulate a desired immune response. A rigorous bioinformatical exploration of sequence patterns hidden in peptides that bind to the mouse MHC-I allomorph H-2K(b) is presented. We exemplify and validate these motif findings by systematically dissecting the epitope SIINFEKL and analyzing the resulting fragments for their binding potential to H-2K(b) in a thermal denaturation assay. The results demonstrate that only fragments exclusively retaining the carboxy- or amino-terminus of the reference peptide exhibit significant binding potential, with the N-terminal pentapeptide SIINF as shortest ligand. This study demonstrates that sophisticated machine-learning algorithms excel at extracting fine-grained patterns from peptide sequence data and predicting MHC-I binding peptides, thereby considerably extending existing linear prediction models and providing a fresh view on the computer-based molecular design of future synthetic vaccines. The server for prediction is available at http://modlab-cadd.ethz.ch (SLiDER tool, MHC-I version 2012).
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Antígenos de Histocompatibilidade Classe I/metabolismo , Peptídeos/metabolismo , Animais , Inteligência Artificial , Biologia Computacional , Camundongos , Ligação ProteicaRESUMO
We present the development and application of a new machine-learning approach to exhaustively and reliably identify major histocompatibility complex class I (MHC-I) ligands among all 20(8) octapeptides and in genome-derived proteomes of Mus musculus , influenza A H3N8, and vesicular stomatitis virus (VSV). Focusing on murine H-2K(b), we identified potent octapeptides exhibiting direct MHC-I binding and stabilization on the surface of TAP-deficient RMA-S cells. Computationally identified VSV-derived peptides induced CD8(+) T-cell proliferation after VSV-infection of mice. The study demonstrates that high-level machine-learning models provide a unique access to rationally designed peptides and a promising approach toward "reverse vaccinology".
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Genes MHC Classe I , Antígenos H-2/imunologia , Vírus da Influenza A Subtipo H3N8/imunologia , Oligopeptídeos/imunologia , Proteoma/imunologia , Vesiculovirus/imunologia , Sequência de Aminoácidos , Animais , Inteligência Artificial , Ligantes , Camundongos , Oligopeptídeos/química , Infecções por Orthomyxoviridae/virologia , Infecções por Rhabdoviridae/virologiaRESUMO
Computer algorithms help in the identification and optimization of peptides with desired structure and function. We provide an overview of the current focus of our research group in this field, highlighting innovative methods for peptide representation and de novo peptide generation. Our evolutionary molecular design cycle contains structure-activity relationship modeling by machine-learning methods, virtual peptide generation, activity prediction, peptide syntheses, as well as biophysical and biochemical activity determination. Such interplay between computer-assisted peptide generation and scoring with real laboratory experiments enables rapid feedback throughout the design cycle so that adaptive optimization can take place. Selected practical applications are reviewed including the design of new immunomodulatory MHC-I binding peptides and antimicrobial peptides.
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Peptídeos/química , Algoritmos , Evolução Química , Relação Estrutura-AtividadeRESUMO
Honey is a sweet and healthy food produced by honeybees (Apis mellifera L.) from flower nectars. Using bidimensional zymography, we have detected the, until now unrevealed, proteolytic activities present in row honey samples. The resulting zymograms were specific for each type of the four unifloral honey under study, and enzymes were identified as serine proteases by the use of specific inhibitors. Further, using bidimensional electrophoresis, we have shown that honey proteases are able to degrade the major Royal Jelly proteins and in particular MRPJ-1, the protein that promotes queen differentiation in honeybees. Our findings open new perspectives for the better understanding of honeybee development, social behaviour and role in honey production. The now discovered honey proteases may influence honey properties and quality, and bidimensional zymograms might be useful to distinguish between different honey types, establish their age and floral origin, and allow honey certification.
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Abelhas/enzimologia , Mel , Peptídeo Hidrolases/isolamento & purificação , Serina Proteases , Animais , Cromatografia Líquida de Alta Pressão , Humanos , Peptídeo Hidrolases/metabolismo , Serina Proteases/classificação , Serina Proteases/isolamento & purificação , Inibidores de Serina Proteinase/farmacologiaRESUMO
Phenylketonuria (PKU) is caused by inherited phenylalanine-hydroxylase (PAH) deficiency and, in many genotypes, it is associated with protein misfolding. The natural cofactor of PAH, tetrahydrobiopterin (BH(4)), can act as a pharmacological chaperone (PC) that rescues enzyme function. However, BH(4) shows limited efficacy in some PKU genotypes and its chemical synthesis is very costly. Taking an integrated drug discovery approach which has not been applied to this target before, we identified alternative PCs for the treatment of PKU. Shape-focused virtual screening of the National Cancer Institute's chemical library identified 84 candidate molecules with potential to bind to the active site of PAH. An in vitro evaluation of these yielded six compounds that restored the enzymatic activity of the unstable PAHV106A variant and increased its stability in cell-based assays against proteolytic degradation. During a 3-day treatment study, two compounds (benzylhydantoin and 6-amino-5-(benzylamino)-uracil) substantially improved the in vivo Phe oxidation and blood Phe concentrations of PKU mice (Pah(enu1)). Notably, benzylhydantoin was twice as effective as tetrahydrobiopterin. In conclusion, we identified two PCs with high in vivo efficacy that may be further developed into a more effective drug treatment of PKU.
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Hidantoínas/metabolismo , Fenilalanina Hidroxilase/metabolismo , Fenilcetonúrias/tratamento farmacológico , Uracila/análogos & derivados , Animais , Sítios de Ligação , Biopterinas/análogos & derivados , Biopterinas/metabolismo , Domínio Catalítico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Descoberta de Drogas , Avaliação Pré-Clínica de Medicamentos , Estabilidade Enzimática , Humanos , Hidantoínas/química , Hidantoínas/farmacologia , Hidantoínas/toxicidade , Camundongos , Oxirredução , Fenilalanina/metabolismo , Fenilalanina Hidroxilase/química , Fenilalanina Hidroxilase/deficiência , Fenilalanina Hidroxilase/genética , Fenilcetonúrias/metabolismo , Dobramento de Proteína , Bibliotecas de Moléculas Pequenas , Uracila/química , Uracila/metabolismo , Uracila/farmacologia , Uracila/toxicidadeRESUMO
Modulation of protein-protein interactions (PPI) has emerged as a new concept in rational drug design. Here, we present a computational protocol for identifying potential PPI inhibitors. Relevant regions of interfaces (epitopes) are predicted for three-dimensional protein models and serve as queries for virtual compound screening. We present a computational screening protocol that incorporates two different pharmacophore models. One model is based on the mathematical concept of autocorrelation vectors and the other utilizes fuzzy labeled graphs. In a proof-of-concept study, we were able to identify serine protease inhibitors using a predicted trypsin epitope as query. Our virtual screening framework may be suited for rapid identification of PPI inhibitors and suggesting bioactive tool compounds.
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Epitopos/química , Mimetismo Molecular , Proteínas/química , Modelos Moleculares , SoftwareRESUMO
BACKGROUND: Ecologic and in vitro studies suggest that exposures to plants or soil may influence risk of Kaposi sarcoma (KS). METHODS: In a population-based study of Sicily, we analyzed data on contact with 20 plants and residential exposure to 17 soils reported by 122 classic KS cases and 840 sex- and age-matched controls. With 88 KS-associated herpesvirus (KSHV) seropositive controls as the referent group, novel correlates of KS risk were sought, along with factors distinguishing seronegatives, in multinomial logistic regression models that included matching variables and known KS cofactors - smoking, cortisone use, and diabetes history. All plants were summed for cumulative exposure. Factor and cluster analyses were used to obtain scores and groups, respectively. Individual plants and soils in three levels of exposure with Ptrend ≤ 0.15 were retained in a backward elimination regression model. RESULTS: Adjusted for known cofactors, KS was not related to cumulative exposures to 20 plants [per quartile adjusted odds ratio (ORadj) 0.96, 95% confidence interval (CI) 0.73 - 1.25, Ptrend = 0.87], nor was it related to any factor scores or cluster of plants (P = 0.11 to 0.81). In the elimination regression model, KS risk was associated with five plants (Ptrend = 0.02 to 0.10) and with residential exposure to six soils (Ptrend = 0.01 to 0.13), including three soils (eutric regosol, chromic/pellic vertisol) used to cultivate durum wheat. None of the KS-associated plants and only one soil was also associated with KSHV serostatus. Diabetes was associated with KSHV seronegativity (ORadj 4.69, 95% CI 1.97 - 11.17), but the plant and soil associations had little effect on previous findings that KS risk was elevated for diabetics (ORadj 7.47, 95% CI 3.04 - 18.35) and lower for current and former smokers (ORadj 0.26 and 0.47, respectively, Ptrend = 0.05). CONCLUSIONS: KS risk was associated with exposure to a few plants and soils, but these may merely be due to chance. Study of the effects of durum wheat, which was previously associated with cKS, may be warranted.
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The transmission of drug-resistant HIV-1 strains might compromise the efficacy of current first-line antiretroviral (ARV) regimens. Between 2004 and 2008, HIV-1 reverse transcriptase (RT) and protease (PR) genes of 108 ARV-naive Sicilian patients were amplified and sequenced to describe the prevalence of ARV resistance mutations among HAART-naive HIV-1-infected individuals. The frequency of transmitted drug resistance mutations (DRAMs) was determined by using genotypic interpretation algorithms. The proportion of HAART-naive HIV-1-infected patients in Sicily increased from 18.4% to 23.5% during 2004-2008. Among naive patients, the overall prevalence of DRAMs was 15.7% [17/108; 95% CI: 9.4-24.0]. DRAMs to nonnucleoside reverse transcriptase inhibitors (nNRTI) were detected most frequently [11/108 (10.2%)], of which K103N was the most prevalent (4.6%), whereas the prevalence of DRAMs was lowest for protease inhibitors (PI) [3/108 (2.8%)]. Drug resistance substitutions associated with two or three drug classes were rarely observed. The prevalence of HIV-1 DRAMs in Sicily was relatively higher than that observed in Italy and other European geographic areas and much higher than in resource-limited countries. However, the possible clinical role played by DRAMs in HAART-naive HIV-1-infected individuals will require further assessment.
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Terapia Antirretroviral de Alta Atividade , Farmacorresistência Viral/genética , Infecções por HIV/transmissão , HIV-1/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Inibidores da Protease de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação , Prevalência , Estudos Retrospectivos , Inibidores da Transcriptase Reversa/uso terapêutico , Sicília/epidemiologia , Adulto JovemRESUMO
The seroprevalence of Human Herpes Virus 8 (HHV8) and its transmission pattern were assessed testing serum samples of 120 internationally adopted children (aged 1-15 years) coming from Eastern Europe. Determinations of IgG antibodies against both latent and lytic HHV-8 antigens were performed by indirect immunofluorescence assay. Antibodies were detected only for lytic antigen of the virus in 12.5% of children with a seroprevalence significatively higher (19.6%) in young children (age 1-6). No correlation was observed between HHV8 seropositivity and serological markers for hepatitis A, B and C viruses and Human Immunodeficiency virus. In conclusion, our findings suggest that HHV8 infection is widespread in some populations from the East Europe, and that person to person contacts among children could be considered the predominant mode of HHV8 transmission in younger age.