Modulation of sensory neuron potassium conductances by anandamide indicates roles for metabolites.

BACKGROUND AND PURPOSE: The endogenous cannabinoid anandamide (AEA) acts at cannabinoid (CB(1)) and vanilloid (TRPV(1)) receptors. AEA also shows antinociceptive properties; although the underlying mechanism for this is not fully understood, both CB(1) and TRPV(1) may be involved. Voltage-activated Ca(2+) channels in rat-cultured dorsal root ganglion (DRG) neurons are modulated by AEA. However, AEA in different populations of neurons enhanced or attenuated KCl-evoked Ca(2+) influx; these effects were linked with soma size. The aim of this study was to determine how AEA or its metabolites might produce these variable responses. EXPERIMENTAL APPROACH: The whole cell patch-clamp technique and fura-2 Ca(2+) imaging were used to characterize the actions of AEA on action potential firing and voltage-activated K(+) currents and to determine whether AEA metabolism plays any role in its effects on cultured DRG neurons. KEY RESULTS: AEA attenuated multiple action potential firing evoked by 300 ms depolarizing current commands in a subpopulation of DRG neurons. Application of 1 microM AEA attenuated voltage-activated K(+) currents and the recovery of KCl-evoked Ca(2+) transients. The insensitivity of these responses to the CB(1) receptor antagonist rimonabant (100 nM) and preincubation of DRG neurons with pertussis toxin suggested that these actions are not CB(1) receptor-mediated. Preincubating DRG neurons with the fatty acid amide hydrolase (FAAH) inhibitor phenylmethylsulphonyl fluoride (PMSF) attenuated the inhibitory actions of AEA on K(+) currents and Ca(2+) influx. CONCLUSION AND IMPLICATIONS: These data suggest that the products of AEA metabolism by FAAH contribute to the attenuation of K(+) conductances and altered excitability of cultured sensory neurons.

Control of intraocular pressure after deep sclerectomy.

AIM: To study the long-term outcome of deep sclerectomy in patients with open angle glaucoma. METHODS: Prospective consecutive series of 43 eyes (38 patients) with medically uncontrolled open-angle glaucoma undergoing deep sclerectomy. All patients underwent clinical assessment before and after surgery at day 7 and at months 1, 3, 6, 12, 18, 24, 36. Surgical success was considered if the patient's intraocular pressure (IOP) < 22 mmHg and the IOP was lowered by more than 20% without the use of any medication. Kaplan-Meier survival curves were used to evaluate the success rate. RESULTS: The mean follow-up time was 28.1 +/- 8.2 months. Mean IOP decreased significantly from a preoperative value of 24.6 +/- 5.5 mmHg to a postoperative value of 18.5 +/- 4.6 mmHg at 36 months (P < 0.001). Microperforation of TDM occurred in three cases (7.0%) and ciliary body prolapse in one case (2.3%) but did not prevent completion of the operation. Postoperatively, hyphaema was detected in one case and shallow anterior chamber in another case and both were treated conservatively. Bleb encapsulation with elevation of IOP occurred in two cases (4.7%) and was treated with 5-fluorouracil subconjunctival injection. Goniopuncture with neodymium : YAG laser was performed in two cases (4.7%). There were no other late complications with the exception of failure of the operation. On the life-table analysis the success rate at 12, 24, and 30 months were 61.4, 36.6, and 18.9%, respectively. CONCLUSION: Deep sclerectomy reduced the IOP temporarily while minimising the risk of postoperative complications commonly encountered with standard trabeculectomy. However, after long-term follow-up surgery failed to maintain a low IOP.

Ultrasound biomicroscopy in deep sclerectomy.

PURPOSE: To evaluate by ultrasound biomicroscopy (UBM) the anatomical characteristics and the intraocular pressure (IOP) lowering mechanisms of deep sclerectomy after long-term follow-up. METHODS: In all, 22 eyes of 21 consecutive patients who had deep sclerectomy were examined by UBM. Several UBM variables were prospectively evaluated, including the presence and maximum length and height of the intrascleral space, the minimum thickness of residual trabeculo-Descemet membrane (TDM), the presence and type of subconjunctival filtering bleb, and the presence of other possible drainage sites, for example suprachoroidal. Surgical success was considered to be achieved when the IOP was <22 mmHg and the IOP was lowered by more than 20% without the use of any medication. The possible association between UBM variables and the surgical outcome was determined. RESULTS: The mean time between surgery and the UBM examination was 12.0+/-5.3 months. The mean IOP decreased significantly from a preoperative value of 23.7+/-4.0 to 16.0+/-3.9 mmHg at the time of UBM (P<0.01). There was a poor correlation between the level of IOP at the time of UBM and the length of intrascleral space (r2=0.0016), the height of the intrascleral space (r2=0.136), or the thickness of remaining TDM (r2=0.0009). The presence and type of filtering bleb were not associated with the success. CONCLUSIONS: In patients undergoing deep sclerectomy, UBM examination after long-term follow-up showed the presence of an intrascleral space and a filtering bleb in most patients. The surgical outcome was not associated with the UBM variables of the surgical area.