38 research outputs found

    A comparative study of the hydrogen-bonding patterns and prototropism in solid 2-thiocytosine (potential antileukemic agent) and cytosine, as studied by 1H-14N NQDR and QTAIM/ DFT

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    A potential antileukemic and anticancer agent, 2-thiocytosine (2-TC), has been studied experimentally in the solid state by 1H-14N NMR-NQR double resonance (NQDR) and theoretically by the quantum theory of atoms in molecules (QTAIM)/density functional theory (DFT). Eighteen resonance frequencies on 14N were detected at 180 K and assigned to particular nitrogen sites (−NH2, –N=, and –NH–) in 2-thiocytosine. Factors such as the nonequivalence of molecules (connected to the duplication of sites) and possible prototropic tautomerism (capable of modifying the type of site due to proton transfer) were taken into account during frequency assignment. The result of replacing oxygen with sulfur, which leads to changes in the intermolecular interaction pattern and molecular aggregation, is discussed. This study demonstrates the advantages of combining NQDR and DFT to extract detailed information on the H-bonding properties of crystals with complex H-bonding networks. Solid-state properties were found to have a profound impact on the stabilities and reactivities of both compounds

    Gene Transcription Changes in Asthmatic Chronic Rhinosinusitis with Nasal Polyps and Comparison to Those in Atopic Dermatitis

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    Asthmatic chronic rhinosinusitis with nasal polyps (aCRSwNP) is a common disruptive eosinophilic disease without effective medical treatment. Therefore, we sought to identify gene expression changes, particularly those occurring early, in aCRSwNP. To highlight expression changes associated with eosinophilic epithelial inflammation, we further compared the changes in aCRSwNP with those in a second eosinophilic epithelial disease, atopic dermatitis (AD), which is also closely related to asthma.Genome-wide mRNA levels measured by exon array in both nasosinus inflamed mucosa and adjacent polyp from 11 aCRSwNP patients were compared to those in nasosinus tissue from 17 normal or rhinitis subjects without polyps. Differential expression of selected genes was confirmed by qRT-PCR or immunoassay, and transcription changes common to AD were identified. Comparison of aCRSwNP inflamed mucosa and polyp to normal/rhinitis tissue identified 447 differentially transcribed genes at > or = 2 fold-change and adjusted p-value < 0.05. These included increased transcription of chemokines localized to chromosome 17q11.2 (CCL13, CCL2, CCL8, and CCL11) that favor eosinophil and monocyte chemotaxis and chemokines (CCL18, CCL22, and CXCL13) that alternatively-activated monocyte-derived cells have been shown to produce. Additional transcription changes likely associated with Th2-like eosinophilic inflammation were prominent and included increased IL1RL1 (IL33 receptor) and EMR1&3 and decreased CRISP2&3. A down-regulated PDGFB-centric network involving several smooth muscle-associated genes was also implicated. Genes at 17q11.2, genes associated with alternative activation or smooth muscle, and the IL1RL1 gene were also differentially transcribed in AD.Our data implicate several genes or gene sets in aCRSwNP and eosinophilic epithelial inflammation, some that likely act in the earlier stages of inflammation. The identified gene expression changes provide additional diagnostic and therapeutic targets for aCRSwNP and other eosinophilic epithelial diseases

    Eozinofilna upala u alergijskom rinitisu i nosnoj polipozi

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    On histopathological examination, nasal polyps and nasal mucosa in allergic rhinitis show different forms of pseudostratified respiratory epithelium, whereas the dominant characteristic of lamina propria is an eosinophilic infiltration. The aim of this study was to compare interleukin (IL)-5 and eosinophilic cationic protein (ECP) levels in the nasal fluid of 42 patients: 12 with allergic rhinitis and nasal septal deviation, 17 non-atopic patients with nasal polyposis, and 13 atopic nasal polyp patients were enrolled in this cross-sectional study. Nasal secretion samples were collected a few days before surgery. The levels of IL-5 were measured using fl ow cytometry and the ECP using a commercial ELISA kit. In addition, we counted eosinophils in hematoxylin-and-eosin-stained sections of all nasal polyp and all nasal mucosa samples taken from the inferior nasal turbinates during septoplasty. A significantly higher concentration of IL-5 was found in the nasal fluid of atopic patients with nasal polyposis than in non-atopic nasal polyp patients (p=0.025) and patients with allergic rhinitis (p=0.05). ECP was higher in atopic nasal polyp patients than in patients with allergic rhinitis (p<0.0001) and than in non-atopic nasal polyp patients (p<0.0001). Polyp eosinophils were higher in atopic’ than in non-atopic patients (p<0.0001) and higher than in the mucosa of patients with allergic rhinitis (p<0.0001). These however had signifi cantly more mucosal eosinophils than was found in the polyps of non-atopic patients’ (p=0.025). ECP levels in nasal fl uid and eosinophil counts in tissue specimens correlated well in all three groups of patients. Our study has shown that atopic nasal polyp patients have a higher level of eosinophilic inflammation than non-atopic patients with nasal polyps and patients with allergic rhinitis.Na histopatoloơkim pregledima nosni polipi, kao i nosna sluznica u alergijskom rinitisu pokazuju različite oblike pseudoslojevitog respiracijskog epitela, dok je osnovna karakteristika lamine proprije infiltracija eozinofilima. Cilj ove studije bio je usporediti koncentracije interleukina 5 (IL-5) i eozinofilnoga kationskog proteina (ECP) u nosnome sekretu pacijenata s alergijskim rinitisom, neatopičnih i atopičnih pacijenata s nosnom polipozom, kao i usporediti broj eozinofi la u tkivu nosnih polipa/nosne sluznice ovih pacijenata. Četrdeset dvoje (n=42) pacijenata, 12-ero s alergijskim rinitisom i devijacijom nosnog septuma, 17-ero neatopičnih pacijenata s nosnom polipozom i 13-ero atopičnih pacijenata s nosnom polipozom bilo je uključeno u ovu presječnu studiju. Uzorci nosnog sekreta bili su skupljeni iz nosnih ơupljina svih ispitanika nekoliko dana prije kirurơkog liječenja. Koncentracije IL-5 mjerene su metodom protočne citometrije, dok su koncentracije ECP mjerene komercijalnim ELISA-kitom. Eozinofi li su brojeni u svim uzorcima tkiva nosnih polipa, kao i u svim uzorcima tkiva sluznice uzetih s donje nosne ơkoljke tijekom septoplastike. Značajno viơe koncentracije IL-5 izmjerene su u nosnom sekretu atopičnih pacijenata s nosnom polipozom u usporedbi s neatopičnim pacijentima s nosnom polipozom (p=0,025) i pacijentima s alergijskim rinitisom (p=0,05). Naơi su rezultati pokazali viơe koncentracije ECP u atopičnih pacijenata s nosnom polipozom nego u pacijenata s alergijskim rinitisom (p<0,0001) i u usporedbi s nealergičnim pacijentima s nosnom polipozom (p<0,0001). Veći broj eozinofi la izbrojen je u tkivu polipa atopičnih pacijenata nego u tkivu polipa neatopičnih pacijenata (p<0,0001), kao i u sluznici pacijenata s alergijskim rinitisom (p<0,0001). U nosnoj sluznici pacijenata s alergijskim rinitisom naơli smo značajno veći broj eozinofila nego u polipima neatopičnih pacijenata s nosnim polipima (p=0,025). Konačno, naơli smo pozitivnu korelaciju između nivoa ECP u nosnom sekretu i broja eozinofila u uzorcima tkiva u sve tri skupine ispitanika. Zaključili smo da atopični pacijenti s nosnom polipozom imaju viơi stupanj eozinofilne upale u usporedbi s neatopičnim pacijentima s nosnim polipima i s pacijentima s alergijskim rinitisom

    International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

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    Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

    MATRIX ISOLATION STUDIES OF NUCLEIC ACID CONSTITUENTS. I. INFRARED SPECTRA OF URACIL MONOMERS

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    Author Institution: Institute of Physics, Polish Academy of Sciences; Department of Chemistry, University of FloridaResults of infrared studies of uracil and its N1,N3N_{1},N_{3}-dideuterated homologue isolated in argon and nitrogen matrices are presented and discussed in terms of normal modes predicted by quantum mechanical calculations .The effects on the spectrum of N-deuteration and of the interaction between the isolated molecule and the matrix are discussed. The quantum mechanical calculations are used to make a resonably reliable first assignment absorption bands to all the normal modes for the matrix-isolated uracil molecule. The wave numbers and relative intensities for the absorption bands for the isolated molecule are related to those reported previously for uracil in the solid phase or in polar solution but differ significantly from them
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