S D Gilbert | PubMed Health

PubMed2005

Riboswitches: natural SELEXion.

Advances in our knowledge of the structure and chemistry of RNA have been harnessed in the process known as SELEX to develop artificial RNA-based molecules that can act as enzymes and ligand binders performing a wide variety of functions. The discovery of riboswitches, natural RNA aptamers involved in genetic regulation, offers a basis of comparison between the artificial selection and the natural selection of structured RNAs for small-molecule recognition. The guanine riboswitch structural determination allows us to draw conclusions regarding the apparent increased complexity of the riboswitch aptamers compared to their in-vitro-selected cousins.

Aptamers, Nucleotide↗

PubMed2001

Antihyperalgesic activity of epibatidine in the formalin model of facial pain.

A growing body of evidence supports a nicotinic cholinergic approach to pain management, as neuronal nicotinic receptor agonists have shown efficacy across animal models of both inflammatory and neuropathic pain. However, most of these investigations have focused on the spinal system, and there is to date no report of nicotinic receptor-mediated antinociception in any pain model involving the trigeminal field of innervation. Thus, the purpose of the present studies was to evaluate whether the neuronal nicotinic receptor agonist epibatidine possesses antihyperalgesic activity in the formalin model of facial pain. Adult, male, Sprague--Dawley rats received a 50-microl, subcutaneous injection of 5% formalin into one vibrissal pad and the consequent, facial grooming behavior was monitored. Consistent with previous investigations using the formalin model, animals exhibited two periods of nocifensive grooming: (1) an acute phase that began immediately, peaked at 3 min and almost completely abated by 6 min, and (2) a tonic phase that began between 6 and 9 min, peaked at 21 min and slowly diminished over the ensuing 24 min. The subcutaneous administration of epibatidine (1--5 microg/kg) 5 min prior to the formalin injection led to a significant, dose-dependent reduction of both the acute and tonic phases of hyperalgesia. Separate groups of animals receiving epibatidine either 15, 30 or 60 min prior to the formalin injection exhibited a progressively diminishing antihyperalgesic response that was no longer significant in either phase by 30 min. Finally, pretreatment with the selective neuronal nicotinic receptor antagonist mecamylamine completely abolished the antihyperalgesic effect of epibatidine in both phases. Taken together, these studies demonstrate that in both the acute and tonic phases of the formalin model of facial pain, epibatidine produces a neuronal nicotinic receptor-mediated antihyperalgesia that is both dose- and time-dependent. These results support the rationale for exploring the clinical efficacy of nicotinic agonists as analgesics to treat certain types of trigeminal pain in humans.

Analgesics, Non-Narcotic↗

PubMed2001

Coronal leakage following three obturation techniques.

AIM: To compare coronal bacterial and India ink leakage in three different obturation techniques with the smear layer having been removed. METHODOLOGY: Seventy extracted single-rooted teeth were instrumented to an apical preparation size 7 Profile Series 29 (Tulsa Dental Products, Tulsa, OK, USA). The smear layer was removed and 20 teeth were randomly obturated with lateral compaction, 20 teeth with vertical compaction, and 20 teeth with Thermafil (Tulsa Dental Products, Tulsa OK, USA). Ten teeth were used for positive (five teeth) and negative (five teeth) controls. Teeth were stored for 90 days in 100% humidity, then subjected coronally to Proteus vulgaris for 21 days to assess bacterial leakage. Following bacterial challenge, India ink was placed coronally for a further 21 days, then scored according to depth of dye leakage. RESULTS: Vertical compaction leaked significantly less than lateral compaction during bacterial challenge. However, when dye was used there were no significant differences. CONCLUSIONS: Bacterial leakage and dye leakage demonstrated considerable variability. The use of a dye following bacterial testing may highlight the failure of experimental devices and vertical root fractures, thus avoiding false positive results found with bacterial testing alone.

Carbon↗