Biomedical subjects

Mark A Connell

Publications and source records attributed to Mark A Connell.

4 recordsLinked to original sources

PubMed2006

Biexponential fitting of diffusion-ordered NMR data: practicalities and limitations.

High resolution diffusion-ordered NMR spectroscopy (HR-DOSY) generally uses monoexponential fitting of the diffusional attenuation of pulsed-field gradient stimulated echo spectra and can, thus, only give proper separation of signals in the diffusion domain where the individual peaks are well-resolved in the spectral domain. In principle, it should be possible to resolve the decays of coincident spectral peaks by multiexponential fitting, but the well-known fundamental difficulties in such a separation are exacerbated by instrumental distortions of the signal decay. The limitations imposed on biexponential fitting by finite signal-to-noise ratio and by the distortion of the theoretical form of the signal attenuation as a result of pulsed-field gradient nonuniformity are explored, and the improvement in DOSY spectra produced using biexponential fitting afforded by compensating for the latter are illustrated.

1-Propanol↗

PubMed2005

The effects of a selective dopamine D2 receptor agonist on behavioral and pathological outcome in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated squirrel monkeys.

In this study, we investigated antiparkinsonian activity of the novel, highly selective dopamine D(2) receptor agonist sumanirole compared with two clinically effective dopaminergic therapies in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of Parkinson's disease. Squirrel monkeys were rendered parkinsonian by chronic administration of MPTP and subsequently dosed with vehicle, L-DOPA plus carbidopa (L-DOPA), ropinirole, or sumanirole over a duration of 8 weeks. Antiparkinsonian effects measured with a parkinsonian primate rating scale (PPRS) showed that sumanirole elicited improved functional outcome compared with vehicle. The dopamine D2/D3 agonist ropinirole improved behavioral outcome similar to sumanirole, whereas L-DOPA treatment yielded the most significant symptomatic improvement. The relative rank of therapies that elicited normalization of PPRS was L-DOPA > sumanirole; ropinirole did not normalize PPRS in any of the treated monkeys. Dyskinesias were present with L-DOPA treatment but were not observed in sumanirole-, ropinirole-, or placebo-treated primates. Pathologically, all MPTP-treated animals displayed neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta and reactive astrocytosis. Neurons immunoreactive with antibodies to the nuclear transcription factor DeltaFosB were most significantly increased in the striatum of L-DOPA-treated monkeys. These results suggest that sumanirole can exert antiparkinsonian effects similar to L-DOPA without the behavioral and morphological consequences of the latter.

Animals↗

PubMed2005

Expression of GAD65 and GAD67 immunoreactivity in MPTP-treated monkeys with or without L-DOPA administration.

This study investigated the consequences of levodopa treatment on the expression of the 65- and 67-kDa isoforms of glutamate decarboxylase (GAD65 and GAD67) immunoreactivity in the basal ganglia and cortex of monkeys rendered Parkinsonian by systemic MPTP administration. All MPTP-treated monkeys showed Parkinsonian impairment and selective loss of tyrosine hydroxylase (TH) with sparing of GAD immunoreactive (-ir) fibers and terminals in basal ganglia. The distribution of GAD65- and GAD67-ir in the cortex, caudate, and putamen was not significantly different in MPTP vs. naïve monkeys nor as a function of L-DOPA treatment. In comparison, the expression of GAD67- but not GAD65-ir was augmented in the globus pallidus in MPTP-treated monkeys. Quantification revealed significant increases in number of GAD67-ir neurons in the external and internal segments of the globus pallidus while no significant difference in the number of GAD65-ir neurons was observed. L-DOPA treatment did not significantly change the number of GAD65- or GAD67-ir pallidal neurons following MPTP. These results support and extend the findings that transcriptional elevation of GAD67 occurs in the globus pallidus and demonstrate that GAD65 and GAD67 are differentially altered following lesion. The finding of elevated GAD67 expression in the pallidum is consistent with alterations in inhibitory neurocircuitry playing a key role in the pathophysiology of motor disturbances in Parkinson's disease.

Animals↗

PubMed2004

NMR measurements of diffusion in concentrated samples: avoiding problems with radiation damping.

Pulsed field gradient spin echo NMR is generally the method of choice for diffusion measurements on liquid samples. With modern high field instruments, however, severe problems can arise when it is applied to samples with very high proton concentrations because of the presence of radiation damping. The problems may be greatly reduced by a suitable choice of experimental parameters, in particular the use of modified stimulated echo pulse sequences with a reduced flip angle for the first pulse.

Journal Article↗