Biomedical subjects

Paul F Smith

Publications and source records attributed to Paul F Smith.

57 records · Page 4Linked to original sources

PubMed2002

Application of real-time quantitative polymerase chain reaction to quantification of glutamate receptor gene expression in the vestibular brainstem and cerebellum.

Reverse transcription-polymerase chain reaction (RT-PCR) is a powerful tool to detect specific gene expression from a small amount of tissue, which is superior to the traditional RNA assays such as Northern blotting and in situ hybridization (ISH) in terms of sensitivity. However, conventional RT-PCR is not suitable for quantification due to its exponential nature. Recently, a real-time quantitative PCR method has been developed to overcome the weak points of RT-PCR, e.g. quantification. Here we describe the use of real-time quantitative PCR using a fluorescent TaqMan probe, to study the regional differences in expression of glutamate receptor subunit/subtype genes (NR1, NR2A, GluR2, KA2, mGluR1, mGluR7) in the central vestibular system including the vestibular nucleus complex, inferior olive and cerebellar flocculus. We found that real-time quantitative PCR yielded similar results to other techniques such as ISH but offered several advantages in terms of relative speed and ability to detect low levels of gene expression. We suggest that real-time quantitative PCR is a useful method to study gene expression for other neurotransmitter receptors in the vestibular brainstem and cerebellum, and is also expected to be more accurate to assess the changes in gene expression following any treatment.

Animals↗

PubMed2002

The contribution of the intrinsic excitability of vestibular nucleus neurons to recovery from vestibular damage.

Damage to the peripheral vestibular system results in a syndrome of ocular motor and postural abnormalities that partially and gradually abate over time in a process known as 'vestibular compensation'. The first, rapid, phase of compensation has been associated with a recovery of spontaneous resting activity in the ipsilateral vestibular nucleus complex (VNC), as a consequence of neuronal and synaptic plasticity. Increasing evidence suggests that normal VNC neurons in labyrinthine-intact animals, as well as ipsilateral VNC neurons following unilateral vestibular deafferentation (UVD), rely to some extent on intrinsic pacemaker activity provided by voltage-dependent conductances for their resting activity. Modification of this intrinsic pacemaker activity may underlie the recovery of resting activity that occurs in ipsilateral VNC neurons following UVD. This review summarizes and critically evaluates the 'intrinsic mechanism hypothesis', identifying discrepancies amongst the current evidence and suggesting experiments that may test it further.

Action Potentials↗

PubMed2002

Cannabinoids in the treatment of pain and spasticity in multiple sclerosis.

There is a large amount of evidence to support the view that the psychoactive ingredient in cannabis, delta9-tetrahydrocannabinol (delta9-THC), and cannabinoids in general, can reduce muscle spasticity and pain under some circumstances. Cannabinoid (CB1) receptors in the CNS appear to mediate both of these effects and endogenous cannabinoids may fulfil these functions to some extent under normal circumstances. However, in the context of multiple sclerosis (MS), it is still questionable whether cannabinoids are superior to existing, conventional medicationsfor the treatment of spasticity and pain. In the case of spasticity, there are too few controlled clinical trials to draw any reliable conclusion at this stage. In the case of pain, most of the available trials suggest that cannabinoids are not superior to existing treatments; however, few trials have examined chronic pain syndromes that are relevant to MS. Whether or not cannabinoids do have therapeutic potential in the treatment of MS, a further issue will be whether synthetic cannabinoids should be used in preference to cannabis itself. Smoking cannabis is associated with significant risks of lung cancer and other respiratory dysfunction. Furthermore, delta9-THC, as a broad-spectrum cannabinoid receptor agonist, will activate both CB1 and CB2 receptors. Synthetic cannabinoids, which target specific cannabinoid receptor subtypes in specific parts of the CNS, are likely to be of more therapeutic use than delta9-THC itself. If rapid absorption is necessary, such synthetic drugs could be delivered via aerosol formulations.

Analgesics, Non-Narcotic↗