Reproducibility of tract‐specific magnetization transfer and diffusion tensor imaging in the cervical spinal cord at 3 tesla

Damage to specific white matter tracts within the spinal cord can often result in the particular neurological syndromes that characterize myelopathies such as traumatic spinal cord injury. Noninvasive visualization of these tracts with imaging techniques that are sensitive to microstructural integrity is an important clinical goal. Diffusion tensor imaging (DTI)‐ and magnetization transfer (MT)‐derived quantities have shown promise in assessing tissue health in the central nervous system. In this paper, we demonstrate that DTI of the cervical spinal cord can reliably discriminate sensory (dorsal) and motor (lateral) columns. From data derived from nine healthy volunteers, two raters quantified column‐specific parallel (λ_||) and perpendicular (λ_?) diffusivity, fractional anisotropy (FA), mean diffusivity (MD), and MT‐weighted signal intensity relative to cerebrospinal fluid (MTCSF) over two time‐points separated by more than 1 week. Cross‐sectional means and standard deviations of these measures in the lateral and dorsal columns were as follows: λ_||: 2.13 ± 0.14 and 2.14 ± 0.11 μm²/ms; λ_?: 0.67 ± 0.16 and 0.61 ± 0.09 μm²/ms; MD: 1.15 ± 0.15 and 1.12 ± 0.08 μm²/ms; FA: 0.68 ± 0.06 and 0.68 ± 0.05; MTCSF: 0.52 ± 0.05 and 0.50 ± 0.05. We examined the variability and interrater and test‐retest reliability for each metric. These column‐specific MR measurements are expected to enhance understanding of the intimate structure‐function relationship in the cervical spinal cord and may be useful for the assessment of disease progression. Copyright © 2009 John Wiley & Sons, Ltd.     

Analgesic activity and opiate receptor affinity of new derivatives of N-butylpiperidine

The three newly synthesized derivatives of N-butylpiperidine 1-butyl-4-phenyl-4-isonicotinoylaminoethylpiperidine (BG 25), 1-buty-isonicotinoylpiperidine (BG 26) and N-(1-butyl-4-phenyl-4-piperidinoyl) tetrahydropapaverine (BG 9) were evaluated for analgesic activity and opiate receptor affinity. All the three compounds showed analgesic activity both in hot-plate and flinch-squeak-jump test in mice, BG 9 being the most potent. The affinity of the compounds to opiate receptor was moderate (in comparison with pentazocine): the affinity of BG 9 was much greater than that of BG 25 and BG 26. The compounds showed a pronounced inhibitory action in stimulated guinea-pig ileum preparation; this was reversible by naloxone. As evaluated on pA basis, all three investigated compounds showed moderate antagonistic activity. Also in this respect BG 9 was more active than the other two compounds. Cholinolytic and strong spasmolytic properties were observed in isolated rat ileum preparation for BG 9 only.     

Novel 4-aryl-pyrido[1,2-c]pyrimidines with dual SSRI and 5-HT(1A) activity. part 3

A number of 4-aryl-5,6,7,8-tetrahydropyrido[1,2-c]pyrimidine with 3-(1,2,3,6-tetrahydro-pyridin-4-yl)-1H-indole or 2-methyl-3-(1,2,3,6-tetrahydro-pyridin-4-yl)-1H-indole residues were synthesized for further investigation of SAR in a group of pyrido[1,2-c]pyrimidine derivatives with dual 5-HT_1A/SERT activity. Compounds 8a-8p were found to be potent ligands for both 5-HT_1A and SERT with K_i ranging from 28,3 to 642 nM and 42,4 nM-1,8 μM, respectively. Moreover compounds 8a, 8b, 8c, 8d, 8e and 8g were found to be selective agonists, while 8i as an antagonist of 5-HT_1A presynaptic receptors in the inducible hypothermia test in mice.     

The role of the nurse in an ambulatory stroke and cognition clinic

In this paper we described our approach to the development of the role of a nurse within a stroke and cognition ambulatory clinic at Baycrest. In developing this approach we integrated Baycrest's commitment to clients and family-focused care, our focus on interdisciplinary collaborative practice, the position of the post-rehabilitation clinic in the continuum of care, the clinical experience of the nurse and director, and the relevant scholarly literature. The role of the nurses in the stroke and cognition clinic includes assessment, interdisciplinary care planning, client/family support, and knowledge transfer.     

Synthesis and conformation analysis of 3-substituted derivatives of 1H,3H-pyrido[2,3-d] pyrimidin-4-one of expected depressive nervous system. Part III

Four series of new 1-aryl (heteroaryl) piperazinylacetyl derivatives of 1H,3H-pyrido[2,3-d] pyrimidin-4-one VIIa-o were synthesised. Substrates for the synthesis of VIa-d were obtained from the respective 3H-pyrido[2.3-d]pyrimidines IVa-d in the reaction with NaBH4. Compounds VIa-d were prepared by chloroacetylation. The obtained 1-chloroacetyl derivatives in the reaction with respective aryl (heteroaryl) piperazine formed 1-aminoacetyl derivatives of 2-phenyl-1 H.3H-pyrido[2.3-d]pyrimidin-4-one compounds VII1a-n. The structure ol compounds was analysed by 1H, 13C NMR spectroscopy.     

Novel 4-aryl-pyrido[1,2-c]pyrimidines with dual SSRI and 5-HT1A activity: Part 2

Derivatives of 4-aryl-5,6,7,8-tetrahydro-pyrido[1,2-c]pyrimidine were synthesized. These compounds contain the 3-(4-piperidyl)-1H-indole residue or its 5-methoxy or 2-methyl derivative. In vitro binding tests were performed to determine the affinity of the compounds for the 5-HT_1A receptor and serotonin transporter (SERT) proteins in the rat brain cortex. In vivo studies, particularly the inducible hypothermia test and forced swimming test, were conducted to determine agonistic/antagonistic activity with pre- and postsynaptic 5-HT_1A receptors. Molecular modeling techniques were used to determine the binding modes of the selected compounds at the 5-HT_1A receptor and SERT. The SAR analysis showed that the presence of the 3-(4-piperidyl)-1H-indole group or its 5-methoxy derivative, as well as a para substitution with –OCH₃ or –F in the aryl ring of 4-aryl-5,6,7,8-tetrahydro-pyrido[1,2-c]pyrimidine, results in an increased affinity for both the 5-HT_1A receptors and SERT. In contrast, the presence of the 2-methyl-3-(4-piperidyl)-1H-indole group resulted in a considerable decrease in binding affinity.