Local anaesthetic techniques and pulsatile ocular blood flow.
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AIM: To compare pulsatile ocular blood flow (POBF) and intraocular pressure (IOP) between eyes of patients receiving either peribulbar (with and without balloon compression) or subconjunctival local anaesthesia (LA). METHODS: 30 eyes of 30 patients undergoing cataract surgery by phacoemulsification were investigated in a study of parallel group design. Ten patients had peribulbar LA and 10 minutes compression with a Honan's balloon (group A). A further 10 patients who received peribulbar LA alone (group B) acted as controls for the effects of balloon compression. Ten other patients were given subconjunctival LA (group C). POBF and IOP were measured using a modified Langham pneumatonometer. Three measurements were made in each eye, the first recording immediately before LA, the second 1 minute after, and the third 10 minutes after LA. RESULTS: No significant change in POBF or IOP was recorded in eyes receiving subconjunctival LA. In the peribulbar groups (A and B), there was a drop in median POBF of 252 and 138 microl/min respectively 1 minute after LA, which was statistically significant in both groups (p<0. 01). By 10 minutes, POBF tended to return to baseline levels, but remained significantly reduced in group B (p<0.05). In addition, there was a significant (p<0.05) reduction in IOP (mean drop of 4.82 mm Hg) in group A following peribulbar LA with balloon compression. CONCLUSIONS: POBF was significantly reduced after peribulbar LA but was unchanged after subconjunctival LA. Balloon compression reduced IOP and improved POBF following peribulbar LA. The findings may have clinical implications in patients with compromised ocular circulation or significant glaucomatous optic neuropathy. (+info)
Inter-relations between the phospholipids of rat pancreatic islets during glucose stimulation, and their response to medium inositol and tetracaine.
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1. Isolated rat pancreatic islets subjected to an increase in glucose concentration from 0.5 to 3 mg/ml showed an increased insulin secretion and 32P-labelling of their phospholipids, especially of phosphatidylinositol, phosphatidylethanolamine, phosphatidylglycerol, and CDP diglyceride. Neither fructose or inositol produced a similar effect. 2. The enhanced labelling of CDP diglyceride and phosphatidylglycerol was suppressed by adding inositol (0.1 mg/ml), while the phosphatidylinositol labelling was increased still further. 3. Tetracaine (0.5 mM), an antagonist of insulin secretion, inhi-ited phosphatidylinositol synthesis while phosphatidylglycerol, CDP diglyceride and phosphatidic acid formation were markedly increased. These effects on phospholipid synthesis were substantially reversed by adding inositol to the medium. Tetracaine also prevented the catabolism of phosphatidylinositol in prelabelled islets but this inhibiton was not reversed by inositol. 4. Inositol addition did not affect insulin secretion in glucose-stimulated islets nor secretion in tetracaine-treated islets. This need not exclude a possible role for heightened phosphatidylinositol cleavage in stimulated insulin secretion. (+info)
Mutation of a single residue in the S2-S3 loop of CNG channels alters the gating properties and sensitivity to inhibitors.
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We previously found that native cyclic nucleotide-gated (CNG) cation channels from amphibian rod cells are directly and reversibly inhibited by analogues of diacylglycerol (DAG), but little is known about the mechanism of this inhibition. We recently determined that, at saturating cGMP concentrations, DAG completely inhibits cloned bovine rod (Brod) CNG channels while only partially inhibiting cloned rat olfactory (Rolf) channels (Crary, J.I., D.M. Dean, W. Nguitragool, P.T. Kurshan, and A.L. Zimmerman. 2000. J. Gen. Phys. 116:755-768; in this issue). Here, we report that a point mutation at position 204 in the S2-S3 loop of Rolf and a mouse CNG channel (Molf) found in olfactory epithelium and heart, increased DAG sensitivity to that of the Brod channel. Mutation of this residue from the wild-type glycine to a glutamate (Molf G204E) or aspartate (Molf G204D) gave dramatic increases in DAG sensitivity without changing the apparent cGMP or cAMP affinities or efficacies. However, unlike the wild-type olfactory channels, these mutants demonstrated voltage-dependent gating with obvious activation and deactivation kinetics. Interestingly, the mutants were also more sensitive to inhibition by the local anesthetic, tetracaine. Replacement of the position 204 glycine with a tryptophan residue (Rolf G204W) not only gave voltage-dependent gating and an increased sensitivity to DAG and tetracaine, but also showed reduced apparent agonist affinity and cAMP efficacy. Sequence comparisons show that the glycine at position 204 in the S2-S3 loop is highly conserved, and our findings indicate that its alteration can have critical consequences for channel gating and inhibition. (+info)
Topical amethocaine gel for pain relief of heel prick blood sampling: a randomised double blind controlled trial.
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BACKGROUND: Heel prick blood sampling is a commonly performed and painful procedure in the newborn infant. Use of a topical local anaesthetic does not relieve this pain. A 4% w/w amethocaine gel (Ametop) reduces the pain of venepuncture in the newborn but has not been tried with heel pricks. AIM: To investigate the effect of topical amethocaine gel on the pain of heel prick in the newborn infant. DESIGN: Randomised, double blind, placebo controlled trial. SUBJECTS: Sixty newborn infants, gestation 28-42 weeks (median 36), postnatal age 1-16 days (median 5) undergoing routine heel prick blood sampling. METHODS: A 1.5 g portion of 4% w/w amethocaine gel or placebo was applied to the skin under occlusion for one hour, then wiped away. Heel prick blood sampling with a spring loaded lance was performed five minutes later. The procedure was videotaped and pain assessed at one second intervals using an adaptation of the neonatal facial coding system (NFCS). No or minimal pain was defined as a cumulative score of less than 5 (out of 15) in the three seconds after firing of the lance and as lack of a cry in the first five seconds. RESULTS: In terms of a low NFCS core and lack of cry (p = 0.12) 20 of 30 (67%) in the amethocaine group and 13 of 29 (45%) in the placebo group had no or minimal pain in response to the heel prick. The median cumulative NFCS score over the three seconds after firing the lance was 3 (interquartile range 0-6) in the amethocaine group compared with 5 (interquartile range 1-10) in the placebo group (p = 0.07). These differences are not significant. CONCLUSIONS: Topical amethocaine gel does not have a clinically important effect on the pain of heel prick blood sampling and its use for this purpose cannot therefore be recommended. Alternative approaches to the relief of pain from this procedure should be explored. (+info)
Charge movements in intact amphibian skeletal muscle fibres in the presence of cardiac glycosides.
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1. Intramembrane charge movements were examined in intact voltage-clamped amphibian muscle fibres following treatment with cardiac glycosides in the hypertonic gluconate-containing solutions hitherto reported to emphasise the features of q(gamma) at the expense of q(beta) charge. 2. The application of chlormadinone acetate (CMA) at concentrations known selectively to block Na(+)-K(+)-ATPase conserved the steady-state voltage dependence of intramembrane charge, contributions from delayed (q(gamma)) charging transients, and their inactivation characteristics brought about by shifts in holding potential. 3. The addition of either ouabain (125, 250 or 500 nM) or digoxin (5 nM) at concentrations previously reported additionally to influence excitation-contraction coupling similarly conserved the steady-state charge-voltage relationships, Q(V), in fully polarised fibres to give values of maximum charge, Q(max), transition voltage, V*, and steepness factor, k, that were consistent with a persistent q component as reported on earlier occasions (Q(max) approximately = 25-27 nC F-1, V* approximately = -45 to -50 mV, k approximately = 7-9 mV). 4. In both cases shifts in holding potential from -90 to -50 mV produced a partial inactivation that separated steeply and more gradually voltage-dependent charge components in agreement with previous characterisations. 5. However, charge movements that were observed in the presence of either digoxin or ouabain were monotonic decays in which delayed (q(gamma)) transients could not be distinguished from the early charging records. These features persisted despite the further addition of chlormadinone acetate over a 10-fold concentration range (5-50 microM) known to displace ouabain from the Na(+)-K(+)-ATPase. 6. Ouabain (500 nM) restored the steady-state charge movement that was previously abolished by the addition of 2.0 mM tetracaine in common with previous results of using ryanodine receptor (RyR)-specific agents. 7. Perchlorate (8.0 mM) restored the delayed 'on' relaxations and increased the prominence of the 'off' decays produced by q(gamma) charge following treatment with cardiac glycosides. This was accompanied by a negative (approximately 10-15 mV) shift in the steady-state charge-voltage relationship but an otherwise conserved maximum charge, Q(max), and steepness factor, k, in parallel with previously reported effects of perchlorate following treatments with RyR-specific agents. 8. The features of cardiac glycoside action thus parallel those of other agents that act on RyR-Ca(2+) release channels yet influence the kinetics but spare the steady-state properties of intramembrane charge. (+info)
Local anesthetic-induced microscopic and mesoscopic effects in micelles. A fluorescence, spin label and SAXS study. Single angle X-ray scattering.
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The interaction of the local anesthetic tetracaine (TTC) with anionic sodium lauryl sulfate (SLS) and zwitterionic 3-(N-hexadecyl-N,N-dimethylammonio)propanesulfonate (HPS) micelles was investigated by fluorescence, spin labeling EPR and small angle X-ray scattering (SAXS). Fluorescence pH titrations allowed the choice of adequate pHs for the EPR and SAXS experiments, where either charged or uncharged TTC would be present. The data also indicated that the anesthetic is located in a less polar environment than its charged counterpart in both micellar systems. EPR spectra evidenced that both anesthetic forms increased molecular organization within the SLS micelle, the cationic form exerting a more pronounced effect. The SAXS data showed that protonated TTC causes an increase in the SLS polar shell thickness, hydration number, and aggregation number, whereas the micellar features are not altered upon incorporation of the uncharged drug. The combined results suggest that the electrostatic interaction between charged TTC and SLS, and the intercalation of the drug in the micellar polar region induce a change in molecular packing with a decrease in the mean cross-sectional area, not observed when the neutral drug sinks more deeply into the micellar hydrophobic domain. In the case of HPS micelles, the EPR spectral changes were small for the charged anesthetic and the SAXS data did not evidence any change in micellar structure, suggesting that this species protrudes more into the aqueous phase due to the lack of electrostatic attractive forces in this system. (+info)
A randomised, double-blind, placebo-controlled, comparative study of topical skin analgesics and the anxiety and discomfort associated with venous cannulation.
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OBJECTIVES: To compare the effect of topical skin anaesthetic agents on the discomfort and anxiety associated with venous cannulation. DESIGN: Randomised, double-blind, placebo-controlled, within subject, volunteer trial. METHODS: 20 healthy volunteers underwent venous cannulation on three separate occasions having received topical skin application of either 4% amethocaine gel (Ametop), 5% eutectic mixture of lidocaine and prilocaine (EMLA) or E45 cream (placebo). Visual analogue and verbal rating scales were used to assess pain and anxiety associated with the venous cannulation, and anticipated anxiety for future cannulation, under each drug condition. RESULTS: Subjects were aged 22-53 years (mean 32.8 years). The mean visual analogue scores (VAS) for discomfort were found to be significantly lower (p< 0.001) with Ametop (VAS = 18mm) and EMLA (VAS = 29mm) compared with the control (VAS = 38mm). There was a positive correlation (R2 = 72%, p<0.001) between discomfort and the predicted anxiety if cannulation was to be repeated with the same cream. With the placebo a positive correlation (R2 = 19.8%, p = 0.05) was found between the level of anxiety before cannulation and the level of discomfort recorded. CONCLUSIONS: Ametop and EMLA topical anaesthetic agents produce effective skin analgesia for venous cannulation. The use of topical analgesia can reduce perceived anxiety about future cannulation procedures. This has application in the management of anxious patients undergoing intravenous sedation, suggesting that topical analgesia prior to venous cannulation may significantly aid anxiolysis. (+info)
Interactions between 3-(Trifluoromethyl)-3-(m-[(125)I]iodophenyl)diazirine and tetracaine, phencyclidine, or histrionicotoxin in the Torpedo series nicotinic acetylcholine receptor ion channel.
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3-(Trifluoromethyl)-3-(m-[(125)I]iodophenyl)diazirine ([(125)I]TID) and [(3)H]tetracaine, an aromatic amine, are noncompetitive antagonists (NCAs) of the Torpedo species nicotinic acetylcholine receptor (nAChR), which have been shown by photoaffinity labeling to bind to a common site in the ion channel in the closed state. Although tetracaine and TID bind to the same site, the amine NCAs phencyclidine (PCP) and histrionicotoxin (HTX), which are also believed to bind within the ion channel, interact competitively with tetracaine but allosterically with TID. To better characterize drug interactions within the nAChR ion channel in the closed state, we identified the amino acids photoaffinity labeled by [(125)I]TID in the presence of tetracaine, PCP, or HTX. In the absence of other drugs, [(125)I]TID reacts with alphaLeu-251 (alphaM2-9) and alphaVal-255 (alphaM2-13) and the homologous residues in each of the other subunits. None of the NCAs shifted the sites of [(125)I]TID labeling to other residues within the ion channel. Tetracaine inhibited [(125)I]TID labeling of M2-9 and M2-13 without changing the relative(125)I incorporation at these positions, whereas PCP and HTX each altered the pattern of [(125)I]TID incorporation at M2-9 and M2-13. These results indicate that tetracaine and TID bind in a mutually exclusive manner to a common site in the closed channel that is spatially separated from the binding sites for PCP and HTX. (+info)