| 1. |
- Aski, Sahar Nikkhou, et al.
(författare)
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Inclusion complexes of cryptophane–E with dichloromethane and chloroform : A thermodynamic and kinetic study using the 1D-EXSY NMR method
- 2008
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Ingår i: Magnetic Resonance in Chemistry. - : Wiley. - 0749-1581 .- 1097-458X. ; 46:12, s. 1135-1140
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Tidskriftsartikel (refereegranskat)abstract
- Complexation equilibria and kinetics of exchange of chloroform and dichloromethane molecules between the cavity of cryptophane-E and bulk solution were investigated using NMR methods. Using one dimensional magnetization transfer (1D-EXSY type sequence), chemical exchange rates were measured in different temperature ranges, limited by the equilibrium constant values of the complexes and the boiling points of the guest substances. From the kinetic data, activation energies were calculated using the Arrhenius equation. From the temperature dependence of the association constant data, the enthalpy and entropy of complexation were estimated and compared with values for similar complexes of other cryptophanes.
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| 2. |
- Aski, Sahar Nikkhou, et al.
(författare)
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Studies of Inclusion Complexes of Dichloromethane in Cryptophanes by Exchange Kinetics and 13C NMR in Solution and the Solid State
- 2008
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Ingår i: Journal of Physical Chemistry C. ; 112, s. 13873-13881
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Tidskriftsartikel (refereegranskat)abstract
- Cryptophanes are molecular hosts having high binding affinities for small, neutral molecules in weakly polar solvents. We have previously studied dichloromethane as a guest inside the cavity of cryptophane-E (cryptophane-333), in solution as well as in the solid state. Here, we present a solution 13C relaxation study of dichloromethane as the guest molecule complexed in the cavity of two smaller hosts: cryptophane-A (cryptophane-222) and cryptophane-223. Carbon-13 relaxation measurements were performed for both guest and host molecules. Exchange kinetics have to be explicitly taken into consideration in order to derive 13C relaxation properties of the bound guest. Rate coefficients were measured using proton 1D-exchange experiments. We have also investigated dichloromethane complexed in the cavity of cryptophane-233 in the solid state, by estimating the motionally averaged 13C-1H dipolar interactions from recoupling experiments under magic angle spinning (MAS) conditions. The measurements for the three cryptophanes provide a consistent set of results for the extent of rotational freedom of the guest inside the host cavities.
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| 3. |
- Counter, S Allen, et al.
(författare)
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Experimental Fusion of Contrast Enhanced High-Field Magnetic Resonance Imaging and High-Resolution Micro-Computed Tomography in Imaging the Mouse Inner Ear
- 2015
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Ingår i: The Open Neuroimaging Journal. - : Bentham Science Publishers Ltd.. - 1874-4400. ; 9, s. 7-12
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Imaging cochlear, vestibular, and 8th cranial nerve abnormalities remains a challenge. In this study, the membranous and osseous labyrinths of the wild type mouse inner ear were examined using volumetric data from ultra high-field magnetic resonance imaging (MRI) with gadolinium contrast at 9.4 Tesla and high-resolution micro-computed tomography (µCT) to visualize the scalae and vestibular apparatus, and to establish imaging protocols and parameters for comparative analysis of the normal and mutant mouse inner ear.METHODS: For in vivo MRI acquisition, animals were placed in a Milleped coil situated in the isocenter of a horizontal 9.4 T Varian magnet. For µCT examination, cone beam scans were performed ex vivo following MRI using the µCT component of a nanoScan PET/CT in vivo scanner.RESULTS: The fusion of Gd enhanced high field MRI and high-resolution µCT scans revealed the dynamic membranous labyrinth of the perilymphatic fluid filled scala tympani and scala vestibule of the cochlea, and semicircular canals of the vestibular apparatus, within the µCT visualized contours of the contiguous osseous labyrinth. The ex vivo µCT segmentation revealed the surface contours and structural morphology of each cochlea turn and the semicircular canals in 3 planes.CONCLUSIONS: The fusion of ultra high-field MRI and high-resolution µCT imaging techniques were complementary, and provided high-resolution dynamic and static visualization of the complex morphological features of the normal mouse inner ear structures, which may offer a valuable approach for the investigation of cochlear and vestibular abnormalities that are associated with birth defects related to genetic inner ear disorders in humans.
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| 4. |
- Counter, S. Allen, et al.
(författare)
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Ultra-high-field (9.4 T) MRI Analysis of Contrast Agent Transport Across the Blood-Perilymph Barrier and Intrastrial Fluid-Blood Barrier in the Mouse Inner Ear
- 2017
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Ingår i: Otology and Neurotology. - 1531-7129 .- 1537-4505. ; 38:7, s. 1052-1059
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Tidskriftsartikel (refereegranskat)abstract
- Hypothesis: Effective paramagnetic contrast agent for the penetration of the perilymphatic spaces of the scala tympani, scala vestibuli, and scala media of the mouse inner ear can be determined using intravenous injection of various gadolinium (Gd) complexes and ultra-high-field magnetic resonance imaging (MRI) at 9.4 Tesla.Background: A number of contrast agents have been explored in experimental high-field MRI to determine the most effective Gd complex for ideal signal-to-noise ratio and maximal visualization of the in vivo mammalian inner ear in analyzing the temporal and spatial parameters involved in drug penetration of the blood-perilymph barrier and intrastrial fluid-blood barrier in the mouse model using MRI.Methods: Gadoteric acid (Dotarem), Gadobutrol (Gadovist), Gadodiamide (Omniscan), Gadopent acid (Magnevist), and Mangafodipir (Teslascan) were administered intravenously using the tail vein of 60 Balb/C mice. High-resolution T1 images of drug penetration were acquired with a horizontal 9.4 T Agilent magnet after intravenously injection. Signal intensity was used as a metric of temporal and spatial parameters of drug delivery and penetration of the perilymphatic and endolymphatic spaces.Results: ANOVA analysis of the area under the curve of intensity enhancement in perilymph revealed a significant difference (p < 0.05) in the scalae uptake using different contrast agents (F (3,25) = 3.54, p = 0.029). The Gadoteric acid complex Dotarem was found to be the most effective Gd compound in terms of rapid, morphological enhancement for analysis of the temporal, and spatial distribution in the perilymphatic space of the inner ear.Conclusion: Gadoteric acid (Dotarem) demonstrated efficacy as a contrast agent for enhanced visualization of the perilymphatic spaces of the inner ear labyrinthine in the mouse, including the scala tympani and scala vestibuli of the cochlea, and the semicircular canals of the vestibular apparatus. These findings may inform the clinical application of Gd compounds in patients with inner ear fluid disorders and vertigo.
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| 5. |
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| 6. |
- Kowalewski, Jozef, et al.
(författare)
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Quinuclidine complex with α-cyclodextrin: a diffusion and 13C NMR relaxation study
- 2008
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Ingår i: Magnetic Resonance in Chemistry. ; 46, s. 261-267
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Tidskriftsartikel (refereegranskat)abstract
- The stability of an inclusion complex of quinuclidine with α-cyclodextrin in solution was investigated by NMR measurements of the translational diffusion coefficient. A 1:1 stoichiometry model yielded an association constant of 35 ± 3 M-1. The guest molecules exchange rapidly between the host cavity and the bulk solution. The reorientational dynamics of the guest and host molecules was studied using carbon-13 NMR relaxation at two magnetic fields. The relaxation of the host nuclei showed very little dependence on the guest–host concentration ratio, while the 13C spins in quinuclidine were sensitive to the solution composition. Using mole-fraction data, it was possible to extract the relaxation parameters for the bound and free form of quinuclidine. Relaxation rates of the guest molecule, free in solution, were best described by an axially symmetric model, while the data of the complex species were analysed using the Lipari–Szabo method. Applying the axially symmetric model to the complexed quinuclidine indicated that the anisotropy of its reorientation in the bound form was increased.
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| 7. |
- Nikkhou Aski, Sahar, 1976-
(författare)
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NMR Studies of Inclusion Compounds
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis presents the application of some of the NMR methods in studying host-guest complexes, mainly in solution. The general focus of the work is on investigating the reorientational dynamics of some small molecules that are bound inside cavities of larger moieties. In the current work, these moieties belong to two groups: cryptophanes and cyclodextrins. Depending on the structure of the cavities, properties of the guest molecules and the formed complexes vary. Chloroform and dichloromethane are in slow exchange between the cage-like cavity of the cryptophanes and the solvent, on the chemical shift time scale, whereas adamantanecarboxylic acid, quinuclidine and 1,7-heptanediol in complex with cyclodextrins are examples of fast exchange. Kinetics and thermodynamics of complexation are studied by measuring exchange rates and translational self-diffusion coefficients by means of 1-dimenssional exchange spectroscopy and pulsed-field gradient (PFG) NMR methods, respectively. The association constants, calculated using the above information give estimates of the thermodynamic stability of the complexes. Carbon-13 spin relaxation data were obtained using conventional relaxation experiments, such as inversion recovery and dynamic NOE, and in some cases HSQC-type (Hetereonuclear Single Quantum Correlation Spectroscopy) experiments. Motional parameters for the free and bound guest, and the host molecules were extracted using different motional models, such as Lipari-Szabo, axially symmetric rigid body, and Clore models. Comparing the overall correlation times and the order parameters of the free and bound guest with the overall correlation time of the host molecule one can estimate the degree of the motional restriction, brought by the complexation, and the coupling between the motion of the bound guest and the reorientation of the host molecule. In one case, the guest motions were also investigated inside the cavities of a solid host material.
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| 8. |
- Pierre, Pernilla Videhult, et al.
(författare)
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High-Dose Furosemide Enhances the Magnetic Resonance Signal of Systemic Gadolinium in the Mammalian Cochlea
- 2020
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Ingår i: Otology and Neurotology. - : LIPPINCOTT WILLIAMS & WILKINS. - 1531-7129 .- 1537-4505. ; 41:4, s. 545-553
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Tidskriftsartikel (refereegranskat)abstract
- Hypothesis:Furosemide alters the permeability of the intrastrial fluid-blood barrier.Background:The cochlear sensory cells are protected by the blood-perilymph and intrastrial fluid-blood barriers, which hinder substances, including gadolinium-based contrast agents (GdCAs), to enter the endolymphatic space. High-dose furosemide causes transient shift of hearing thresholds and morphological changes in stria vascularis. Furosemide is also known to enhance drug-induced ototoxicity.Methods:Furosemide (400mg/kg b.w.) was injected i.v. in Balb/C mice (n=20). Twenty minutes later, the GdCA gadobutrol, gadopentetic acid, or gadoteric acid was injected i.v. The distribution of GdCA to the perilymphatic and endolymphatic spaces was studied with MRI (9.4T) for 250minutes.Results:The perilymphatic and endolymphatic spaces were signal-enhanced in all animals. Gadopentetic acid and gadoteric acid yielded similar signal enhancement in all three scalae, while gadobutrol yielded significantly higher enhancement in scala tympani than scala media (p=0.043) and scala vestibuli (p=0.043). The signal enhancement reached a plateau but did not decrease during the time of observation.Conclusion:Treatment with a high dose of furosemide before injection of a GdCA resulted in enhancement of the MRI signal in the endolymphatic space as well as the perilymphatic space, which supports our hypothesis that furosemide alters the permeability of the intrastrial fluid-blood barrier.
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| 9. |
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| 10. |
- Videhult Pierre, Pernilla, et al.
(författare)
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Middle Ear Administration of a Particulate Chitosan Gel in an in vivo Model of Cisplatin Ototoxicity
- 2019
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Middle ear (intratympanic, IT) administration is a promising therapeutic method as it offers the possibility of achieving high inner ear drug concentrations with low systemic levels, thus minimizing the risk of systemic side effects and drug-drug interactions. Premature elimination through the Eustachian tube may be reduced by stabilizing drug solutions with a hydrogel, but this raises the secondary issue of conductive hearing loss.Aim: This study aimed to investigate the properties of a chitosan-based particulate hydrogel formulation when used as a drug carrier for IT administration in an in vivo model of ototoxicity.Materials and Methods: Two particulate chitosan-based IT delivery systems, Thio-25 and Thio-40, were investigated in albino guinea pigs (n = 94). Both contained the hearing protecting drug candidate sodium thiosulfate with different concentrations of chitosan gel particles (25% vs. 40%). The safety of the two systems was explored in vivo. The most promising system was then tested in guinea pigs subjected to a single intravenous injection with the anticancer drug cisplatin (8 mg/kg b.w.), which has ototoxic side effects. Hearing status was evaluated with acoustically evoked frequency-specific auditory brainstem response (ABR) and hair cell counting. Finally, in vivo magnetic resonance imaging was used to study the distribution and elimination of the chitosan-based system from the middle ear cavity in comparison to a hyaluronan-based system.Results: Both chitosan-based IT delivery systems caused ABR threshold elevations (p < 0.05) that remained after 10 days (p < 0.05) without evidence of hair cell loss, although the elevation induced by Thio-25 was significantly lower than for Thio-40 (p < 0.05). Thio-25 significantly reduced cisplatin-induced ABR threshold elevations (p < 0.05) and outer hair cell loss (p < 0.05). IT injection of the chitosan- and hyaluronan-based systems filled up most of the middle ear space. There were no significant differences between the systems in terms of distribution and elimination.Conclusion: Particulate chitosan is a promising drug carrier for IT administration. Future studies should assess whether the physical properties of this technique allow for a smaller injection volume that would reduce conductive hearing loss.
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