Biomedical subjects
Publications and source records attributed to Christian Beaulieu.
A series of 2-substituted N-benzyl benzimidazole containing molecules has been synthesized and its structure-activity relationship for the human DP receptor has been evaluated. Selective DP antagonists with nanomolar potency for the DP receptor were identified in this novel series of benzimidazoles.
PURPOSE: To determine the relevance of cerebrospinal fluid (CSF)-suppression for the measurement of diffusion anisotropy in well-localized areas of the brain, particularly the subcortical white matter (WM) within the gyri and cortical gray matter (GM), in young and elderly subjects, and to assess the changes of water diffusivity in the brain with normal aging. MATERIALS AND METHODS: Quantitative measures of anisotropy in 26 regions, including subcortical WM (i.e., in the gyri), cortical GM, major deep WM, and deep GM regions of young (21-25 years, N = 8) and elderly (61-74 years, N = 10) normal volunteers, were assessed with CSF-suppressed diffusion tensor imaging (DTI) relative to standard DTI. RESULTS: CSF-suppressed DTI demonstrated significant increases in fractional anisotropy (FA) of 3-12% in the young and 2-14% in the elderly groups with the largest changes being in the subcortical WM of the gyri. Furthermore, FA decreased by 10-19% in the subcortical WM of the gyri of the elderly subjects relative to the young, primarily due to increases in the perpendicular diffusivity, lambda(3), with age. CONCLUSION: CSF-suppressed DTI yields more accurate measures of quantitative anisotropy in cortical and subcortical brain regions. Reductions of anisotropy with aging were predominantly observed in subcortical WM of the gyri.
We used diffusion tensor imaging (DTI) to assess Wallerian degeneration of the pyramidal tract within the first 2 weeks after ischemic stroke, and correlated the extent of Wallerian degeneration with the motor deficit. Nine patients with middle cerebral artery stroke were examined 2-16 days after stroke by DTI and T2-weighted MRI. We measured fractional anisotropy (FA), averaged diffusivity (Dav), eigenvalues of the diffusion tensor and T2-weighted signal in the cerebral peduncle and compared these values between the affected and the unaffected side and between patients and six controls. FA was significantly reduced on the affected side compared to the unaffected side and compared to the control group. The largest eigenvalue was reduced, whereas the smallest eigenvalue was elevated on the affected side. There was no significant difference in T2-weighted signal and Dav. The decrease of anisotropy correlated positively with the motor deficit at the time of DTI study and 90 days after stroke. The reduction of anisotropy mirrors the disintegration of axonal structures, as it occurs in the early phase of Wallerian degeneration. DTI detects changes of water diffusion related to beginning pyramidal tract degeneration within the first 2 weeks after stroke that are not yet visible in conventional T2-weighted or orientationally averaged diffusion weighted MRI. We demonstrated for the first time a correlation of early DTI findings of pyramidal tract damage with the motor deficit. DTI can help prognosing recovery of motor function after stroke within the early subacute phase.
Clinical studies on rt-PA (recombinant tissue-type plasminogen activator) treatment of stroke showed a favorable outcome. However, there are reports of harmful effects of t-PA via the potentiation of excitotoxic injury. We used combined X-ray angiography and MRI imaging to study the balance between the beneficial effect of reperfusion and secondary detrimental effects of rt-PA. Therefore, rats (n=15) were assigned to three groups according to recanalization or lack thereof of the middle cerebral artery (MCA) and rt-PA or saline treatment in an embolic stroke model. Diffusion and perfusion MRI showed that animals had significantly improved perfusion values and final infarct size when recanalization was successful. However, final infarct volumes at 6 h post stroke onset were greater in the rt-PA group compared to controls at comparable perfusion values when the MCA did not recanalize after treatment (67.4+/-5.4 versus 47.7+/-17.9% of ipsilateral hemisphere, P=0.042). Our results demonstrate that the combination of angiography and MR-imaging is useful to further evaluate rt-PA treatment of thromboembolic stroke.
PURPOSE: To demonstrate the feasibility of obtaining high-quality magnetic resonance (MR) images of the human cervical spinal cord in vivo at a magnetic field strength of 3 T and to optimize the signal contrast between gray matter, white matter, and cerebrospinal fluid (CSF) on 2D gradient recalled echo (GRE) images of the cervical spinal cord. MATERIALS AND METHODS: Using a custom-built, anatomically molded radio frequency (RF) surface coil, the repetition time and flip angle of a 2D GRE sequence were systematically varied in five volunteers to assess tissue contrast in the cervical spinal cord. RESULTS: The 2D GRE parameters for an optimal balance between gray-white matter and CSF-white matter contrast at 3 T were determined to be a time-to-repetition (TR) of 2000 msec and a flip angle of 45 degrees, with the constant short time-to-echo (TE) of 12 msec used in this study. Excellent tissue contrast and visualization of the internal anatomy of the spinal cord was demonstrated reproducibly in eight subjects using these optimal parameters. CONCLUSION: This study demonstrates that imaging the cervical spinal cord and delineating internal spinal cord structures such as gray and white matter is feasible at 3 T.
We have developed a highly convergent and stereoselective synthesis of BILA 2157 BS, a potent and orally active renin inhibitor. The synthesis proceeds in 15 distinct chemical steps (with several integrated, multistep operations) from aminodiol 4. The key step in the synthesis involves the use of an enantiospecific, enzyme-catalyzed hydrolysis of a substituted succinate diester to provide a homochiral succinic acid derivative in 98% enantiomeric excess (>/=2.5 kg scale). Recycling of the unwanted enantiomer is accomplished through base-catalyzed racemization, leading to an efficient deracemization of the starting racemic diester. The entire sequence proceeds without chromatographic purifications and delivers the product with >97% homogeneity. In addition, compared to the previously reported syntheses of BILA 2157 BS, this approach avoids the use of expensive chiral auxiliaries and cryogenics and, thus, should be amenable to the preparation of large quantities of this peptidomimetic inhibitor.
Anisotropic water diffusion in neural fibres such as nerve, white matter in spinal cord, or white matter in brain forms the basis for the utilization of diffusion tensor imaging (DTI) to track fibre pathways. The fact that water diffusion is sensitive to the underlying tissue microstructure provides a unique method of assessing the orientation and integrity of these neural fibres, which may be useful in assessing a number of neurological disorders. The purpose of this review is to characterize the relationship of nuclear magnetic resonance measurements of water diffusion and its anisotropy (i.e. directional dependence) with the underlying microstructure of neural fibres. The emphasis of the review will be on model neurological systems both in vitro and in vivo. A systematic discussion of the possible sources of anisotropy and their evaluation will be presented followed by an overview of various studies of restricted diffusion and compartmentation as they relate to anisotropy. Pertinent pathological models, developmental studies and theoretical analyses provide further insight into the basis of anisotropic diffusion and its potential utility in the nervous system.