2,795 research outputs found
Effects of specific allergen immunotherapy on biological markers and clinical parameters in asthmatic children: a controlled-real life study
No full textAbstract Background Allergen-specific immunotherapy (AIT) is the only treatment able to change the natural course of allergic diseases. We aimed at investigating the clinical efficacy of SLITOR (Serbian registered vaccine for sublingual allergen specific immunotherapy). Methods 7–18 years old children with allergic asthma and rhinitis were enrolled and addressed to the active (AIT plus pharmacological treatment) or control (standard pharmacological treatment only) group. Clinical and medications scores, lung function and exhaled FeNO were measured at baseline and at every follow-up. Results There was a significant improvement in both nasal and asthma symptom scores as well as in medication score in SLIT group. SLIT showed an important influence on lung function and airway inflammation. Conclusions Our data showed that SLITOR was effective not only in terms of patient reported outcomes but an improvement of pulmonary function and decrease of lower airway inflammation were also observed
Ideal und/oder Funktion? Zur Wertungsmatrix moralischen Fortschritts am Beispiel der neueren Ideologiekritik
No full textKlement K. Ideal und/oder Funktion? Zur Wertungsmatrix moralischen Fortschritts am Beispiel der neueren Ideologiekritik. In: Reder M, Cojocaru M-D, Filipovic A, Finkelde D, Wallacher J, eds. Jahrbuch Praktische Philosophie in globaler Perspektive. Schwerpunkt Moralischer Fortschritt. Praktische Philosophie in globaler Perspektive. Vol 3. Freiburg / München: Karl Alber; 2019: 73-102
Theoretical and experimental study on theophylline release from stearic acid cylindrical delivery systems
No full textThe purpose of this study is to evaluate the possibility of developing a cylindrical sustained-release dosage form for theophylline directly by means of a ram extrusion process. In particular, the formulations contained: stearic acid as a low melting binder, monohydrate lactose and polyethylene glycol 6000 as hydrophilic fillers. The influence of type and percentage of the components was studied considering different parameters such as the time required for 50% of the drug release (t50%)and the drug diffusion coefficient in the delivery system. The choice of the different formulations to be tested is carried out employing an axial design with constraint domains. The limits of each component were fixed on the basis of preliminary trials. The analysis of the t50% values revealed that the release kinetics is mainly affected by stearic acid and theophylline content, whilst lactose effect is almost negligible. A substantial correspondence between the experimental results and the analysis of the drug release kinetics performed by means of an ad hoc developed mathematical model was found. The proposed mathematical model allows to conclude that wherever the release mechanism is initially ruled by dissolution, then diffusion plays the most important role
Technologies of gender: Soviet literature and film in the 1920s and 1930s
No full textMy dissertation, “Technologies of Gender: Soviet Literature and Film in the 1920s and 1930s,” examines the vital role technology and machines – both actual and imagined – play in defining the ‘new Soviet man’ and ‘new Soviet woman’ in early Soviet culture. As I argue in my dissertation, the period of the 1920s and 1930s witnesses a radical change in the perception of physicality brought about by new technology. My project elucidates how the rise of technology and technological discourse in Soviet culture remakes the body and reconfigures traditional gender roles, producing a Soviet cyborg (in Donna Haraway’s terms), first male, then female.
In the twenties, in order to combat mortality and render the body perfect, male authors engage in writing about sophisticated technologies based on experimental scientific and medical research (as in Pilnyak’s 1928 A Matter of Death and Platonov’s 1927 The Ethereal Tract). These technocratic utopian imaginings introduce the cyborg that has overcome all mortal constraints, including biological procreation (Platonov). While in the predominantly male avant-garde culture women’s role and access to technology are reduced, I show that in socialist realist texts and films of the 1930s, the reverse takes place: women instead of men now have a privileged relationship to machines. Women artists and workers contest the hyper-masculinist culture and through female cyborgism remap their bodies and consciousness to create their own feminist politics (Shaginian’s 1931 novel The Hydroelectric Plant, Shub’s 1932 film K.Sh.E., and Pasha Angelina’s all-female tractor brigade). The official culture of the thirties refashions itself in the feminine idiom to demonstrate that the never-ending advancement under Stalin exceeds the revolutionary achievements of the 1920s. This obsession leads to the creation of the Soviet heroine of labor, the female cyborg embodied in the image of the woman at the tractor wheel riding into the bright future, the ultimate symbol of transformed Stalinist technocratic society (as in Eisenstein’s General Line (1929), Pyriev’s Tractor Drivers (1939), and Alexandrov’s Bright Path (1940). The project considers both well-known and lesser-known writers/texts and films. At stake is a new way of looking at both literature and cinema of the 1920s-1930s from the point of view of gender technologies and technologies of gender.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2021-08-01The student, Marina Filipovic, accepted the attached license on 2019-07-02 at 14:00.The student, Marina Filipovic, submitted this Dissertation for approval on 2019-07-02 at 14:20.This Dissertation was approved for publication on 2019-07-02 at 17:03.DSpace SAF Submission Ingestion Package generated from Vireo submission #14131 on 2019-11-26 at 13:04:20Made available in DSpace on 2019-11-26T20:49:19Z (GMT). No. of bitstreams: 2
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Structural, biological and computational study of oxamide derivative|СТРУКТУРНА, БИОЛОШКА И РАЧУНСКА ИПИТИВАЊА ДЕРИВАТА ОКСАМИДА
No full textA dicarboxylato-diamide-type compound 2,2'-[(1,2-dioxoethane-1,2--diyl)diimino]dibenzoicacid (H(4)obbz) (1) was synthesized and characterized. The crystal structure of K(2)H(2)obbz center dot 2H(2)O (2) was determined by X-ray diffract-tion analysis. The cytotoxic activities of the compounds were tested against four different cancer cell lines MCF-7, A549, HT-29, HeLa and a human nor-mal cell line MRC-5. The results indicate reasonable dose-dependent cytotox-icity of the ligands that show selectivity against the tested carcinoma and healthy cell lines. Flow cytometric analysis and fluorescence microscopy showed that the most active compound, H(4)obbz, induced apoptosis and G0/G1 cell cycle arrest, indicating blockage of DNA synthesis as a possible mechanism that trig-gers apoptosis. Docking and molecular dynamics simulations gave similar res-ponses regarding interactions (binding) between their ligands and chaperon Grp78. The MMGBSA determined Delta G binding energies were in the range from -104 to -140 kJ mol(-1)
Selenotriapine – An isostere of the most studied thiosemicarbazone with pronounced pro-apoptotic activity, low toxicity and ability to challenge phenotype reprogramming of 3-D mammary adenocarcinoma tumors
No full textTriapine, the most studied α-N-heterocyclic thiosemicarbazone, revealed potent activity against advanced leukemia, but was ineffective against a variety of solid tumors. Moreover, methemoglobinemia, which is a side effect of triapine administration, may limits all clinical application. To enhance anticancer activity and reduce side effects, we applied an isosteric replacement of sulfur to selenium atom was performed by synthesis and characterization of selenium triapine analog, 3-aminopyridine-2-carboxaldehyde selenosemicarbazone (selenotriapine). Compared to triapine, selenotriapine revealed superior pro-apoptotic activity with activation of intrinsic apoptotic pathway in both human monocytic leukemia (THP-1) and mammary adenocarcinoma (MCF-7) cell lines. For MCF-7 2-D cultures, selenotriapine induced notable increase in mitochondrial superoxide radical generation and dissipation of mitochondrial transmembrane potential. A significant delay in growth of MCF-7 spheroids (3-D culture) was accompanied by phenotypic stem cell reprogramming (Oct-4 expression). Additionally, selenotriapine demonstrated a very low toxicity profile as compared to triapine, confirmed over alleviated extent of methemoglobin formation and higher IC50 value in brine shrimp cytotoxicity assay
Small Molecule Inhibitors of Protein-Protein Interactions
No full textProtein-protein interactions (PPIs) constitute a rising class of targets for the next generation of therapeutic intervention. Though they play a fundamental role in many biological processes and almost all pathological conditions including cancer, diabetes, and autoimmune diseases, , PPIs remain underrepresented in drug discovery. Small molecules are the ideal candidates for PPI inhibitors due to low production cost and better absorption, distribution, metabolism, and excretion (ADME) properties compared to biological agents. Discovering small molecule inhibitors of PPIs has proven to be difficult because of the relatively large contact areas between proteins. Herein are described novel approaches to the chemical synthesis as well as a screening tool which will facilitate the discovery of small molecule inhibitors of PPIs.
Currently, molecules derived from multicomponent reactions (MCRs) are rarely distributed in general screening libraries. The exceptions are special scaffolds, e.g. dihydropyrimidines, whose class includes the blockbuster Ca antagonist, Nifedipine. Interestingly, however, MCR molecules have been frequently described as inhibitors of PPIs. Examples include p53/mdm21,2, Bcl23, HIV-1/gp414, CCR55 and oxytocin antagonists6. These findings support the notion that MCR molecules are especially suitable for mimicking peptides. We have developed a virtual library of scaffolds derived from a diverse set of MCRs which are easily chemically accessible.
In addition, our lab has set forth to discover novel MCRs to add to our virtual library. One such scaffold described in this dissertation is derived from the Ugi-4-component-5-cenetered reaction. A novel amidation of this classic scaffold adds a true four-component reaction to our MCR database. The scope and limitations of this reaction are described in detail allowing for an accurate representation of compounds with a high probability of being synthesized. Various cyclizations of this scaffold are also explored and described in detail.
A receptor-based drug discovery approach can be applied when an accurate three-dimensional (3D) structure of a specific PPI complex is available. A novel, complementary and transformative docking approach for the rational design of small molecule inhibitors was developed for our virtual library based on the “anchor” concept. Applying our method, we efficiently discovered several new scaffolds of inhibitors of the p53/MDM2 interaction with lower micromolar affinity binding to MDM2, which can serve as starting point for medicinal chemistry optimization.
In summary, the methods and tools described in this dissertation are important contributions to the fields of medicinal chemistry and structure-based drug discovery because they combine structural insights and ligand design to expedite the discovery of novel small molecule inhibitors of PPIs
CABLE-SUSPENDED CPR-D TYPE PARALLEL ROBOT
No full textThis paper deals with the analysis and synthesis of a newly selected Cable-suspended Parallel Robot configuration, named CPR-D system. The camera carrier workspace has the shape of a parallelepiped. The CPR-D system has a unique Jacobian matrix that maps the relationship between internal and external coordinates. This geometric relationship is a key solution for the definition of the system kinematic and dynamic models. Because of the CPR-D system complexity, the Lagrange principle of virtual work has been adapted. Two significant Examples have been used for the CPR-D system analysis and validation
Preparation and in vitro/in vivo characterisation of a melt pelletised paracetamol/stearic acid sustained delivery system
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