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101.
Emanuela Foglia Paolo Bonfanti Giuliano Rizzardini Erminio Bonizzoni Umberto Restelli Elena Ricci Emanuele Porazzi Francesca Scolari Davide Croce 《PloS one》2013,8(2)
Objective
To estimate the lifetime cost utility of two antiretroviral regimens (once-daily atazanavir plus ritonavir [ATV+r] versus twice-daily lopinavir/ritonavir [LPV/r]) in Italian human immunodeficiency virus (HIV)-infected patients naïve to treatment.Design
With this observational retrospective study we collected the clinical data of a cohort of HIV-infected patients receiving first-line treatment with LPV/r or ATV+r.Methodology
A Markov microsimulation model including direct costs and health outcomes of first- and second-line highly active retroviral therapy was developed from a third-party (Italian National Healthcare Service) payer’s perspective. Health and monetary outcomes associated with the long-term use of ATV+r and LPV/r regimens were evaluated on the basis of eight health states, incidence of diarrhoea and hyperbilirubinemia, AIDS events, opportunistic infections, coronary heart disease events and, for the first time in an economic evaluation, chronic kidney disease (CKD) events. In order to account for possible deviations between real-life data and randomised controlled trial results, a second control arm (ATV+r 2) was created with differential transition probabilities taken from the literature.Results
The average survival was 24.061 years for patients receiving LPV/r, 24.081 and 24.084 for those receiving ATV+r 1 and 2 respectively. The mean quality-adjusted life-years (QALYs) were higher for the patients receiving LPV/r than those receiving ATV+r (13.322 vs. 13.060 and 13.261 for ATV+r 1 and 2). The cost-utility values were 15,310.56 for LPV/r, 15,902.99 and 15,524.85 for ATV+r 1 and 2.Conclusions
Using real-life data, the model produced significantly different results compared with other studies. With the innovative addition of an evaluation of CKD events, the model showed a cost-utility value advantage for twice-daily LPV/r over once-daily ATV+r, thus providing evidence for its continued use in the treatment of HIV. 相似文献102.
Ammazzalorso A Amoroso R Baraldi M Bettoni G Braghiroli D De Filippis B Duranti A Moretti M Tortorella P Tricca ML Vezzalini F 《Bioorganic & medicinal chemistry letters》2002,12(5):817-821
The chiral analogues of gemfibrozil 5-(2,5-dimethylphenoxy)-2-methylpentanoic acid and 5-(2,5-dimethylphenoxy)-2-ethylpentanoic acid were synthesized in optically active form using (S)-4-(1-methylethyl)-2-oxazolidinone as chiral auxiliary. All compounds inhibit human platelet aggregation. From these data, one can surmise that all tested compounds and gemfibrozil act at the platelet level with different mechanism than that of ASA, even if with a different potency. 相似文献
103.
Maurizio Onisto Paola Zeilante Paolo Scannapieco Donatella Pellati Monica Pozza Cristina Caenazzo Alessandro Negro Spiridione Garbisa 《Experimental cell research》1998,242(2):451
A novel 44-kDa gene product (D123) has been proposed as necessary for S-phase entry of the cell cycle: a point mutation resulted in a temperature-sensitive arrest in G1-phase. From human fibrosarcoma cDNA library, we have isolated an identical gene and studied its sequence and mRNA and protein expression. Compared withD123,three nucleotide differences within the human coding sequence, plus others, result in a change of two amino acids. A partial sequence similarity has been found with a yeast gene of unknown function. The protein has several potential phosphorylation sites, is highly hydrophilic, and may be highly structured in α-helix. The mRNA is abundantly expressed by a variety of normal and transformed cells and by all tissues examined, being most highly expressed in testis. Specific antibodies, raised against a rhD123 polypeptide, recognize a major 42- to 44-kDa molecule in crude extract of various human cell lines. Immunohistochemistry reveals that D123 protein is not homogeneously expressed: it is detected, often in granular vescicles, in the cytoplasm of some epithelial, stromal, and sperm cells and in varicosities lining nervous fibers, while it appears to be absent in nuclei, endothelial, and smooth muscle cells. The precise link between cytoplasmic occurrence of D123 and cell cycle progression still remains to be clarified. 相似文献
104.
Urmila Saha Asma Yasmeen Khan Sutanwi Bhuiya Suman Das Gaetano Fiorillo Paolo Lombardi 《Journal of biomolecular structure & dynamics》2019,37(6):1375-1389
Study on bioactive molecules, capable of stabilizing G-Quadruplex structures is considered to be a potential strategy for anticancer drug development. Berberrubine (BER) and two of its analogs bearing alkyl phenyl and biphenyl substitutions at 13-position were studied for targeting human telomeric G-quadruplex DNA sequence. The structures of berberrubine and analogs were optimized by density functional theory (DFT) calculations. Time-dependent DFT (B3LYP) calculations were used to establish and understand the nature of the electronic transitions observed in UV–vis spectra of the alkaloid. The interaction of berberrubine and its analogs with human telomeric G-quadruplex DNA sequence 5′-(GGGTTAGGGTTAGGGTTAGGG)-3′ was investigated by biophysical techniques and molecular docking study. Both the analogs were found to exhibit higher binding affinity than natural precursor berberrrubine. 13-phenylpropyl analog (BER1) showed highest affinity [(1.45 ± 0.03) × 105 M?1], while the affinity of the 13-diphenyl analog (BER2) was lower at (1.03 ± 0.05) × 105 M?1, and that of BER was (0.98 ± 0.03) × 105 M?1. Comparative fluorescence quenching studies gave evidence for a stronger stacking interaction of the analog compared to berberrubine. The thiazole orange displacement assay has clearly established that the analogs were more effective in displacing the end stacked dye in comparison to berberrubine. Molecular docking study showed that each alkaloid ligand binds primarily at the G rich regions of hTelo G4 DNA which makes them G specific binder towards hTelo G4 DNA. Isothermal titration calorimetry studies of quadruplex–berberrubine analog interaction revealed an exothermic binding that was favored by both enthalpy and entropy changes in BER in contrast to the analogs where the binding was majorly enthalpy dominated. A 1:1 binding stoichiometry was revealed in all the systems. This study establishes the potentiality of berberrubine analogs as a promising natural product based compounds as G-quadruplex-specific ligands. 相似文献
105.
Sanna D Lai T Francalacci P Curini-Galletti M Casu M 《Genetics and molecular biology》2009,32(4):864-867
Monocelis lineata consists of a complex of sibling species, widespread in the Mediterranean and Atlantic Ocean. Previous genetic analysis placed in evidence at least four sibling species. Nevertheless, this research was not conclusive enough to fully resolve the complex or to infer the phylogeny/phylogeography of the group. We designed specific primers aiming at obtaining partial sequences of the mtDNA gene Cytochrome c Oxidase subunit I (COI) of M. lineata, and have identified 25 different haplotypes in 32 analyzed individuals. The dendrogram generated by Neighbor-Joining analysis confirmed the differentiation between Atlantic and Mediterranean siblings, as well as the occurrence of at least two Mediterranean sibling species. Thus validated, the method here presented appears as a valuable tool in population genetics and biodiversity surveys on the Monocelis lineata complex. 相似文献
106.
Global conservation priorities for marine turtles 总被引:2,自引:0,他引:2
Wallace BP DiMatteo AD Bolten AB Chaloupka MY Hutchinson BJ Abreu-Grobois FA Mortimer JA Seminoff JA Amorocho D Bjorndal KA Bourjea J Bowen BW Briseño Dueñas R Casale P Choudhury BC Costa A Dutton PH Fallabrino A Finkbeiner EM Girard A Girondot M Hamann M Hurley BJ López-Mendilaharsu M Marcovaldi MA Musick JA Nel R Pilcher NJ Troëng S Witherington B Mast RB 《PloS one》2011,6(9):e24510
Where conservation resources are limited and conservation targets are diverse, robust yet flexible priority-setting frameworks are vital. Priority-setting is especially important for geographically widespread species with distinct populations subject to multiple threats that operate on different spatial and temporal scales. Marine turtles are widely distributed and exhibit intra-specific variations in population sizes and trends, as well as reproduction and morphology. However, current global extinction risk assessment frameworks do not assess conservation status of spatially and biologically distinct marine turtle Regional Management Units (RMUs), and thus do not capture variations in population trends, impacts of threats, or necessary conservation actions across individual populations. To address this issue, we developed a new assessment framework that allowed us to evaluate, compare and organize marine turtle RMUs according to status and threats criteria. Because conservation priorities can vary widely (i.e. from avoiding imminent extinction to maintaining long-term monitoring efforts) we developed a “conservation priorities portfolio” system using categories of paired risk and threats scores for all RMUs (n = 58). We performed these assessments and rankings globally, by species, by ocean basin, and by recognized geopolitical bodies to identify patterns in risk, threats, and data gaps at different scales. This process resulted in characterization of risk and threats to all marine turtle RMUs, including identification of the world''s 11 most endangered marine turtle RMUs based on highest risk and threats scores. This system also highlighted important gaps in available information that is crucial for accurate conservation assessments. Overall, this priority-setting framework can provide guidance for research and conservation priorities at multiple relevant scales, and should serve as a model for conservation status assessments and priority-setting for widespread, long-lived taxa. 相似文献
107.
Federico Fogolari Haritha Haridas Alessandra Corazza Paolo Viglino Davide Corà Michele Caselle Gennaro Esposito Luigi E Xodo 《BMC structural biology》2009,9(1):64-20
Background
Independent surveys of human gene promoter regions have demonstrated an overrepresentation of G3X n1G3X n2G3X n3G3 motifs which are known to be capable of forming intrastrand quadruple helix structures. In spite of the widely recognized importance of G-quadruplex structures in gene regulation and growing interest around this unusual DNA structure, there are at present only few such structures available in the Nucleic Acid Database. In the present work we generate by molecular modeling feasible G-quadruplex structures which may be useful for interpretation of experimental data. 相似文献108.
Structural and functional link between the mitochondrial network and the endoplasmic reticulum 总被引:1,自引:0,他引:1
Carlotta Giorgi Diego De Stefani Angela Bononi Rosario Rizzuto Paolo Pinton 《The international journal of biochemistry & cell biology》2009,41(10):1817-1827
Mitochondrial and endoplasmic reticulum (ER) networks are fundamental for the maintenance of cellular homeostasis and for determination of cell fate under stress conditions. Recent structural and functional studies revealed the interaction of these networks. These zones of close contact between ER and mitochondria called MAM (mitochondria associated membranes) support communication between the two organelles including bioenergetics and cell survival. The existence of macromolecular complexes in these contact sites has also been revealed. In this contribution, we will review: (i) the ER and mitochondria structure and their dynamics, (ii) the basic principles of ER mitochondrial Ca2+ transport, (iii) the physiological/pathological role of this cross-talk. 相似文献
109.
110.
Ascenzi P Bocedi A Visca P Altruda F Tolosano E Beringhelli T Fasano M 《IUBMB life》2005,57(11):749-759
Release of hemoglobin into plasma is a physiological phenomenon associated with intravascular hemolysis. In plasma, stable haptoglobin-hemoglobin complexes are formed and these are subsequently delivered to the reticulo-endothelial system by CD163 receptor-mediated endocytosis. Heme arising from the degradation of hemoglobin, myoglobin, and of enzymes with heme prosthetic groups could be delivered in plasma. Albumin, haptoglobin, hemopexin, and high and low density lipoproteins cooperate to trap the plasma heme, thereby ensuring its complete clearance. Then hemopexin releases the heme into hepatic parenchymal cells only after internalization of the hemopexin-heme complex by CD91 receptor-mediated endocytosis. Moreover, alpha1-microglobulin contributes to heme degradation by a still unknown mechanism, with the concomitant formation of heterogeneous yellow-brown kynurenine-derived chromophores which are very tightly bound to amino acid residues close to the rim of the lipocalin pocket. During hemoglobin synthesis, the erythroid alpha-chain hemoglobin-stabilizing protein specifically binds free alpha-hemoglobin subunits limiting the free protein toxicity. Although highly toxic because capable of catalyzing free radical formation, heme is also a major and readily available source of iron for pathogenic organisms. Gram-negative bacteria pick up the heme-bound iron through the secretion of a hemophore that takes up either free heme or heme bound to heme-proteins and transports it to a specific receptor, which, in turn, releases the heme and hence iron into the bacterium. Here, hemoglobin and heme trapping mechanisms are summarized. 相似文献