169,959 research outputs found
Rosso Fiorentino: architetto "garbatissimo e straordinario" ed "eccellentissimo e straordinario"?
No full textEffects of some antineoplastic drugs (vincristine, doxorubicin and epirubicin) on human platelet aggregation
No full textThe analysis of cellular transcriptional response at the genome level : two case studies with relevance to bacterial pathogenesis
No full textCatheter inversion during cavotricuspid isthmus catheter ablation: the new shaft visualization catheter reduces fluoroscopy use
No full textAims: Catheter ablation (CA) is the choice therapy of cavotricuspid isthmus (CTI) atrial flutter. The aim of this study was to describe our approach to improve the CTI ablation using a zero-fluoroscopy (ZF). The procedural difficulties could be related to anatomical characteristics of the CTI. Methods: One hundred eighty-eight patients that performed CA of CTI were retrospectively and consecutively evaluated between 2017 and 2019. The studied population was divided into two groups. Eighty-eight patients who were undergone CA using ablation catheter without shaft visualization catheter (NSV) were Group 1. One hundred patients were undergone CA using ablation catheter with a shaft visualization (SV); they were Group 2. The catheter was looped at the Eustachian ridge after 200 seconds of radiofrequencies (RF) without elimination of local electrogram. Results: A conduction line block of CTI was obtained in all patients of Group 2 using a ZF approach. In 16 patients of Group 1, the catheter inversion was obtained using fluoroscopy to avoid damages during its loop. In Group 2, a complete CTI block was obtained with a catheter inversion approach in ten patients without fluoroscopy, visualizing the shaft and the tip of the ablation catheter on the electroanatomic (EAM) map. In the overall population studied the use of SV had a linear correlation with the ZF approach (r =.629; P <.001). The duration of RF was lower in Group 2 than in Group 1 (Group 1: 27.8 ± 6.3 vs Group 2: 15.6 ± 7.2 minutes; P <.01). The procedure time between two groups was lower in Group 2 than in Group 1 (Group 1: 58.4 ± 22.4 vs Group 2: 42.2 ± 15.7 minutes; P <.01). No differences between two groups were documented regarding success and complications. Conclusions: The visualization of the shaft's catheter on the EAM permitted the catheter inversion safely in order to overcome some complex CTI anatomy and obtain bidirectional block. The SV reduced procedure time, RF applications and fluoroscopy exposition during CTI ablation. © 2021 The Author
Target-Selective Drug Delivery through Liposomes Labeled with Oligobranched Neurotensin Peptides.
No full textThe structure and the in vitro behavior of liposomes filled with the cytotoxic drug doxorubicin (Doxo) and functionalized on the external surface with a branched moiety containing four copies of the 8-13 neurotensin (NT) peptide is reported. The new functionalized liposomes, DOPC-NT(4) Lys(C(18) )(2) , are obtained by co-aggregation of the DOPC phospholipid with a new synthetic amphiphilic molecule, NT(4) Lys(C(18) )(2) , which contains a lysine scaffold derivatized with a lipophilic moiety and a tetrabranched hydrophilic peptide, NT8-13, a neurotensin peptide fragment well known for its ability to mimic the neurotensin peptide in receptor binding ability. Dynamic light scattering measurements indicate a value for the hydrodynamic radius (RH) of 88.3±4.4 nm. The selective internalization and cytotoxicity of DOPC-NT(4) Lys(C(18) )(2) liposomes containing Doxo, as compared to pure DOPC liposomes, were tested in HT29 human colon adenocarcinoma and TE671 human rhabdomyosarcoma cells, both of which express neurotensin receptors. Peptide-functionalized liposomes show a clear advantage in comparison to pure DOPC liposomes with regard to drug internalization in both HT29 and TE671 tumor cells: FACS analysis indicates an increase in fluorescence signal of the NT(4) -liposomes, compared to the DOPC pure analogues, in both cell lines; cytotoxicity of DOPC-NT(4) Lys(C(18) )(2) -Doxo liposomes is increased four-fold with respect to DOPC-Doxo liposomes in both HT29 and TE671 cell lines. These effects could to be ascribed to the higher rate of internalization for DOPC-NT(4) Lys(C(18) )(2) -Doxo liposomes, due to stronger binding driven by a lower dissociation constant of the NT(4) -liposomes that bind the membrane onto a specific protein, in contrast to DOPC liposomes, which approach the plasma membrane unselectively
Site-specific pegylation of an antimicrobial peptide increases resistance to Pseudomonas aeruginosa elastase
No full textM33 is a branched peptide currently under preclinical characterization for the development of a new antibacterial drug against gram-negative bacteria. Here, we report its pegylation at the C-terminus of the three-lysine-branching core and the resulting increase in stability to Pseudomonas aeruginosa elastase. This protease is a virulence factor that acts by destroying peptides of the native immune system. Peptide resistance to this protease is an important feature for M33-Peg activity against Pseudomona
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Transglutaminase-synthesized spermine derivative of substance P recognizes rat portal vein neurokinin-3 receptors.
No full textThe effects of the transglutaminase-synthesized polyamine derivatives of Substance P (SP) have been further characterized by their ability to contract in vitro the rat portal vein strip (RPV), a pharmacological preparation particularly rich in NK-3 receptors. The effects of selective agonists of NK-1, NK-2 and NK-3 receptors [Sar9,Met(O(2))11]SP, beta-Ala8 NKA(4-10), and senktide respectively, were also evaluated by measuring RPV concentration-response curves. Peptide [GR-82334 (NK-1) and MEN-10,376 (NK-2)] and nonpeptide [WIN 51,708 (NK-1) and SR 142801 (NK-3)] NK receptor antagonists were used to confirm the participation of the different NK receptors to contractile response. Our results demonstrated that the spermine derivative of SP (Spm-SP), previously shown to be unable to recognize NK-1 and NK-2 receptors in some bioassays, contracts RPV (EC50 = 588 nM) better than the native neuropeptide (EC50 = 1120 nM). A pretreatment with thiorphan, an inhibitor of neutral endopeptidases, significantly reduced such a difference. While this inhibitor shifts the SP concentration-response curves to the left (EC50 = 720 nM) the action of Spm-SP and [Sar9,Met(O(2))11]SP were completely thiorphan-resistant. In the absence of thiorphan we found the following rank order of potency: senktide > > beta-Ala8 NKA(4-10) > [Sar9,Met(O(2))11]SP = Spm-SP > SP. Among the mentioned NK receptor antagonists, only the selective NK-3 receptor antagonist, SR 142801, shifted to the right Spm-SP and [Sar9,Met(O(2))11]SP concentration-response curve, showing pKB values of 5.84 and 5.88, respectively. Therefore, the reported results suggest that the introduction of a Spm moiety into the SP alters the parent peptide molecule by increasing its affinity for NK-3 receptors and/or by preventing its degradation by some proteolytic enzymes
Transglutaminase-synthesized spermine derivative of substance P recognizes rat portal vein neurokinin-3 receptors
No full textDesign and in vitro evaluation of branched peptide conjugates:turning nonspecific cytotoxic drugs into tumor-selective agents
No full textThe use of peptide receptors as targets for tumor-selective therapies was envisaged years ago with the findings that receptors for different endogenous regulatory peptides are overexpressed in several primary and metastatic human tumors, and can be used as tumor antigens. Branched peptides can retain or even increase, through multivalent binding, the biological activity of a peptide and are very resistant to proteolysis, thus having a markedly higher in vivo activity compared with the corresponding monomeric peptides. Oligo-branched peptides, containing the human regulatory peptide neurotensin (NT) sequence, have been used as tumor-specific targeting agents. These peptides are able to selectively and specifically deliver effector units, for cell imaging or killing, to tumor cells that overexpress NT receptors. Results obtained with branched NT conjugated to different functional units for tumor imaging and therapy indicate that branched peptides are promising novel multifunctional targeting molecules. This study is focused on the role of the releasing pattern of drug-conjugated branched NT peptides. We present results obtained with oligo-branched neurotensin peptides conjugated to 6-mercaptopurin (6-MP), combretastain A-4 (CA4) and monastrol (MON). Drugs were conjugated to oligo-branched neurotensin through different linkers, and the mode-of-release, together with cytotoxicity, was studied in different human cancer cell lines. The results show that branched peptides are very promising pharmacodelivery options. Among our drug-armed branched peptides, NT4-CA4 was identified as a candidate for further development and evaluation in preclinical pharmacokinetic and pharmacodynamic studies. This peptide-drug exhibits significant activity against pancreas and prostate human cancer cells. Consequently, this derivative is of considerable interest due to the high mortality rates of pancreas neuroendocrine tumors and the high incidence of prostate cancer
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