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31.
Clinical trials use placebos with the assumption that they are inert, thus all placebos are considered to be equal. Here we show that this assumption is wrong and that different placebo procedures are associated to different therapeutic rituals which, in turn, trigger different mechanisms and produce different therapeutic outcomes. We studied high altitude, or hypobaric hypoxia, headache, in which two different placebos were administered. The first was placebo oxygen inhaled through a mask, whereas the second was placebo aspirin swallowed with a pill. Both placebos were given after a conditioning procedure, whereby either real oxygen or real aspirin was administered for three consecutive sessions to reduce headache pain. We found that after real oxygen conditioning, placebo oxygen induced pain relief along with a reduction in ventilation, blood alkalosis and salivary prostaglandin (PG)E2, yet without any increase in blood oxygen saturation (SO2). By contrast, after real aspirin conditioning, placebo aspirin induced pain relief through the inhibition of all the products of cyclooxygenase, that is, PGD2, PGE2, PGF2, PGI2, thromboxane (TX)A2, without affecting ventilation and blood alkalosis. Therefore, two different placebos, associated to two different therapeutic rituals, used two different pathways to reduce headache pain. The analgesic effect following placebo oxygen was superior to placebo aspirin. These findings show that different placebos may use different mechanisms to reduce high altitude headache, depending on the therapeutic ritual and the route of administration. In clinical trials, placebos and outcome measures should be selected very carefully in order not to incur in wrong interpretations. 相似文献
32.
Jacopo Burrello Sara Bolis Carolina Balbi Alessio Burrello Elena Provasi Elena Caporali Lorenzo Grazioli Gauthier Andrea Peirone Fabrizio D'Ascenzo Silvia Monticone Lucio Barile Giuseppe Vassalli 《Journal of cellular and molecular medicine》2020,24(17):9945-9957
The current standard biomarker for myocardial infarction (MI) is high‐sensitive troponin. Although powerful in clinical setting, search for new markers is warranted as early diagnosis of MI is associated with improved outcomes. Extracellular vesicles (EVs) attracted considerable interest as new blood biomarkers. A training cohort used for diagnostic modelling included 30 patients with STEMI, 38 with stable angina (SA) and 30 matched‐controls. Extracellular vesicle concentration was assessed by nanoparticle tracking analysis. Extracellular vesicle surface‐epitopes were measured by flow cytometry. Diagnostic models were developed using machine learning algorithms and validated on an independent cohort of 80 patients. Serum EV concentration from STEMI patients was increased as compared to controls and SA. EV levels of CD62P, CD42a, CD41b, CD31 and CD40 increased in STEMI, and to a lesser extent in SA patients. An aggregate marker including EV concentration and CD62P/CD42a levels achieved non‐inferiority to troponin, discriminating STEMI from controls (AUC = 0.969). A random forest model based on EV biomarkers discriminated the two groups with 100% accuracy. EV markers and RF model confirmed high diagnostic performance at validation. In conclusion, patients with acute MI or SA exhibit characteristic EV biomarker profiles. EV biomarkers hold great potential as early markers for the management of patients with MI. 相似文献
33.
Wen Yongdiao Liu Shaobin Zhang Haifeng Xu Yan Yu Qiming Wang Lingling Frezza Fabrizio 《Plasmonics (Norwell, Mass.)》2020,15(4):1141-1149
Plasmonics - Herein, an integrated multifunctional design for simultaneous perfect absorption and polarization conversion is proposed that worked in the Ku band: the proposed structure consisted of... 相似文献
34.
Fabrizio Gianni Vesna Ma
i Fabrizio Bartolini Alexis Pey Mathieu Laurent Luisa Mangialajo 《Restoration Ecology》2020,28(4):750-756
The role of herbivorous fish in threatening marine forests of temperate seas has been generally overlooked. Only recently, the scientific community has highlighted that high fish herbivory can lead to regime shifts from canopy‐forming algae to less complex turf communities. Here, we present an innovative herbivorous fish deterrent device (DeFish), which can be used for conservation and restoration of marine forests. Compared to most traditional fish exclusion systems, such as cages, the DeFish system does not need regular cleaning and maintenance, making it more cost‐efficient. Resistance of DeFish was tested by installing prototypes at different depths in the French Riviera and in Montenegro: more than 60% of the devices endured several years without maintenance, even if most of them were slightly damaged in the exposed site in Montenegro. The efficacy of DeFish in limiting fish herbivory was tested by an exclusion experiment on Cystoseira amentacea in the French Riviera. In a few months, the number of fish bite marks on the seaweed was decreased, causing a consequent increase in algal length. The device here presented has been conceived for Mediterranean canopy‐forming algae, but the same concept can be applied to other species vulnerable to fish herbivory, such as kelps or seagrasses. In particular, the DeFish design could be improved using more robust and biodegradable materials. Innovative engineering systems, such as DeFish, are expected to become useful tools in the conservation and restoration of marine forests, to complement other practices including active reforestation, herbivore regulation, and regular monitoring of their status. 相似文献
35.
Giovanni Piccinini Mariangela Iannello Guglielmo Puccio Federico Plazzi Justin C Havird Fabrizio Ghiselli 《Molecular biology and evolution》2021,38(6):2597
In Metazoa, four out of five complexes involved in oxidative phosphorylation (OXPHOS) are formed by subunits encoded by both the mitochondrial (mtDNA) and nuclear (nuDNA) genomes, leading to the expectation of mitonuclear coevolution. Previous studies have supported coadaptation of mitochondria-encoded (mtOXPHOS) and nuclear-encoded OXPHOS (nuOXPHOS) subunits, often specifically interpreted with regard to the “nuclear compensation hypothesis,” a specific form of mitonuclear coevolution where nuclear genes compensate for deleterious mitochondrial mutations due to less efficient mitochondrial selection. In this study, we analyzed patterns of sequence evolution of 79 OXPHOS subunits in 31 bivalve species, a taxon showing extraordinary mtDNA variability and including species with “doubly uniparental” mtDNA inheritance. Our data showed strong and clear signals of mitonuclear coevolution. NuOXPHOS subunits had concordant topologies with mtOXPHOS subunits, contrary to previous phylogenies based on nuclear genes lacking mt interactions. Evolutionary rates between mt and nuOXPHOS subunits were also highly correlated compared with non-OXPHO-interacting nuclear genes. Nuclear subunits of chimeric OXPHOS complexes (I, III, IV, and V) also had higher dN/dS ratios than Complex II, which is formed exclusively by nuDNA-encoded subunits. However, we did not find evidence of nuclear compensation: mitochondria-encoded subunits showed similar dN/dS ratios compared with nuclear-encoded subunits, contrary to most previously studied bilaterian animals. Moreover, no site-specific signals of compensatory positive selection were detected in nuOXPHOS genes. Our analyses extend the evidence for mitonuclear coevolution to a new taxonomic group, but we propose a reconsideration of the nuclear compensation hypothesis. 相似文献
36.
Paul R. J. Ames Tommaso Bucci Mira Merashli Marta Amaral Alessia Arcaro Fabrizio Gentile 《Free radical research》2013,47(10):1063-1082
AbstractSystemic sclerosis (SSc) is a multisystem autoimmune disease: characterised from the clinical side by progressive vasculopathy and fibrosis of the skin and different organs and from the biochemical side by fibroblast deregulation with excessive production of collagen and increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4). The latter contributes to an overproduction of reactive oxygen species that through an autocrine loop maintains NOX4 in a state of activation. Reactive oxygen and nitrogen species are implicated in the origin and perpetuation of several clinical manifestations of SSc having vascular damage in common; attempts to dampen oxidative and nitrative stress through different agents with antioxidant properties have not translated into a sustained clinical benefit. Objective of this narrative review is to describe the origin and clinical implications of oxidative and nitrative stress in SSc, with particular focus on the central role of NOX4 and its interactions, to re-evaluate the antioxidant approaches so far used to limit disease progression, to appraise the complexity of antioxidant treatment and to touch on novel pathways elements of which may represent specific treatment targets in the not so distant future. 相似文献
37.
Giuseppe Battistoni Fabrizio Cappucci Nicola Bertolino Maria Grazia Brambilla Hae Song Mainardi Alberto Torresin 《Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)》2013,29(6):656-661
The purpose of this work is to investigate the capability of the FLUKA Monte Carlo (MC) code to simulate the Elekta Leksell Gamma Knife Perfexion (LGK-PFX) and reproduce the Treatment Planning System (TPS) Leksell GammaPlan version 8.2 (LGP) dose calculations for the case of a water equivalent phantom target. Thanks to the collaboration with Elekta Instruments AB, the collimation system geometry, the source positions and all the involved material have been simulated in detail. The relative linear dose distribution along the three coordinate axes, for each collimator size, and the Relative Output Factors (ROF) have been investigated. The simulation has been validated comparing simulated linear dose profiles with measurements performed with EBT radiochromic films. The acceptance criterion between experimental data and FLUKA results is based on the gamma index (GI) method. The FLUKA MC calculation for the ROF provided the values of 0.920 for the 8 mm collimators and 0.800 for the 4 mm collimators. These values are in good agreement with the Elekta reference data of 0.924 and 0.805 respectively. The percentage difference between calculated and reference values for the ROF is under 1% and within the FLUKA uncertainty. Also the simulated relative dose profiles show a good agreement with the LGP calculation expressed by means of the gamma index method. This established accuracy proves that FLUKA is a suitable and powerful tool in order to reproduce successfully the LGP calculations for the homogeneous media. 相似文献
38.
Claudiu T. Supuran Andrea Scozzafava Marc A. Ilies Fabrizio Briganti 《Journal of enzyme inhibition and medicinal chemistry》2013,28(4):381-401
A new approach is proposed for the selective in vivo inhibition of membrane-bound versus cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isozymes with a class of positively-charged, membrane-impermeant sulfonamides. Aromatic/heterocyclic sulfonamides acting as strong (but unselective) inhibitors of this zinc enzyme were derivatized by the attachment of trisub-stituted-pyridinium-ethylcarboxy moieties (obtained from 2, 4, 6–trisubstituted-pyrylium salts and β-alanine) to the amino, imino, hydrazino or hydroxyl groups present in their molecules. Efficient in vitro inhibition (in the nanomolar range) was observed with some of the new derivatives against three investigated CA isozymes, i.e., hCA I, hCA II (cytosolic forms) and bCA IV (membrane-bound isozyme; h = human; b = bovine isozyme). Due to their salt-like character, the new type of inhibitors reported here, unlike the classical, clinically used compounds (such as acetazolamide, methazolamide, ethoxzolamide), are unable to penetrate biological membranes, as shown by CJ vivo and in vivo perfusion experiments in rats. The level of bicarbonate excreted into the urine of the experimental animals perfused with solutions of the new and classical inhibitors suggest that: (i) when using the new type of positively-charged sulfonamides. only the membrane-bound enzyme (CA IV) was inhibited. whereas the cytosolic isozymes (CA I and II) were not affected, (ii) in the experiments in which the classical compounds (acetazolamide, bcn-zolamíde. etc.) were used. unselective inhibition of all CA isozymes (I. II and IV) occurred. 相似文献
39.
A potentiated cooperation of carbonic anhydrase IX and histone deacetylase inhibitors against cancer
Jessica Ruzzolini Elena Andreucci Silvia Peppicelli Francesca Bianchini Fabrizio Carta 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):391-397
Abstract The emergence of tumour recurrence and resistance limits the survival rate for most tumour-bearing patients. Only, combination therapies targeting pathways involved in the induction and in the maintenance of cancer growth and progression might potentially result in an enhanced therapeutic efficacy. Herein, we provided a prospective combination treatment that includes suberoylanilide hydroxamic acid (SAHA), a well-known inhibitor of histone deacetylases (HDACs), and SLC-0111, a novel inhibitor of carbonic anhydrase (CA) IX. We proved that HDAC inhibition with SAHA in combination with SLC-0111 affects cell viability and colony forming capability to greater extent than either treatment alone of breast, colorectal and melanoma cancer cells. At the molecular level, this therapeutic regimen resulted in a synergistically increase of histone H4 and p53 acetylation in all tested cell lines. Overall, our findings showed that SAHA and SLC-0111 can be regarded as very attractive combination providing a potential therapeutic strategy against different cancer models. 相似文献
40.
Paolo Vineis Fabrizio Veglia Sisko Anttila Simone Benhamou Margie L. Clapper Vita Dolzan 《Biomarkers》2013,18(3):298-305
Gene–environment interactions have been extensively studied in lung cancer. It is likely that several genetic polymorphisms cooperate in increasing the individual risk. Therefore, the study of gene–gene interactions might be important to identify high-susceptibility subgroups. GSEC is an initiative aimed at collecting available data sets on metabolic polymorphisms and the risks of cancer at several sites and performing pooled analyses of the original data. Authors of published papers have provided original data sets. The present paper refers to gene–gene interactions in lung cancer and considers three polymorphisms in three metabolic genes: CYP1A1, GSTM1 and GSTT1. The present analyses compare the gene–gene interactions of the CYP1A1*2A, GSTM1 and GSTT1 polymorphisms from studies on lung cancer conducted in Europe and the USA between 1991 and 2000. Only Caucasians have been included. The data set includes 1466 cases and 1488 controls. The only clear-cut association was found with CYP1A1*2A. This association remained unchanged after stratification by polymorphisms in other genes (with an odds ratio [OR] of approximately 2.5), except when interaction with GSTM1 was considered. When the OR for CYP1A1*2A was stratified according to the GSTM1 genotype, the OR was increased only among the subjects who had the null (homozygous deletion) GSTM1 genotype (OR=2.8, 95% CI=0.9–8.4). The odds ratio for the interactive term (CYP1A1*2A by GSTM1) in logistic regression was 2.7 (95% CI=0.5–15.3). An association between lung cancer and the homozygous CYP1A1*2A genotype is confirmed. An apparent and biologically plausible interaction is suggested between this genotype and GSTM1. 相似文献