Lung volume reduction surgery for emphysema.
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Humans↗
Biomedical subjects
M Barrington
Publications and source records attributed to M Barrington.
The effect of an interrupted daily period of normal visual stimulation on form deprivation myopia in chicks.
The aim of this study was to determine whether an integrator of neural activity influences the amount of myopia and axial elongation resulting from deprivation of form vision. The effects on ocular parameters of a continuous period of 30 min per day of normal vision was compared to two exposures of 15 min duration each, or three exposures of 10 min each. For the remaining time, chicks had monocular translucent occlusion in a 12 hr light/12 hr dark diurnal cycle, for either 2 or 3 weeks. Fellow eyes and the eyes of bilaterally unoccluded chicks were used as controls. We found that several short periods of normal visual stimulation per day were more effective in preventing the development of form deprivation myopia and axial elongation than was one single period of the same total duration, after both 2 and 3 weeks of treatment. This study suggests that the level of neural activity in the retina may have a cumulative effect in influencing ocular growth.
Animals↗
Noradrenaline release and the effect of endogenous activation of the phospholipase C/protein kinase C signalling pathway in rat atria.
1. It has been proposed that protein kinase C (PKC) in sympathetic nerves is activated during action-potential evoked release of noradrenaline and helps maintain transmitter output. We studied this phenomenon further in rat atria radiolabelled with [3H]-noradrenaline. 2. Noradrenaline release was elevated by continuous electrical stimulation of the atria for 10 min at either 5 or 10 Hz. Two inhibitors of PKC, polymyxin B (21 microM) and Ro 318220 (3 microM), markedly inhibited the release of noradrenaline but only at the higher stimulation frequency. 3. Further experiments were conducted with 10 Hz stimulation but for shorter train durations. In this case polymyxin B inhibited noradrenaline release during a 10 or 15 s train of impulses but not during a 5 s train. This suggests that PKC effects are induced during the stimulation train by some process. 4. The diacylglycerol kinase inhibitor R59949 (10 microM), which prevents the breakdown of diacylglycerol, enhanced noradrenaline release elicited by stimulation at 10 Hz for 10 or 15 s. This effect was not seen if polymyxin B was present and suggests that diacylglycerol is the endogenous activator of PKC. 5. The source of the diacylglycerol may be through phospholipase C pathways, since the phospholipase C inhibitor U73122 (3 microM) inhibited noradrenaline release at 10 Hz for 10 s and the effect was not seen if polymyxin B was also present. 6. It is unlikely that phospholipase D is the source of diacylglycerol. Although the phospholipase D inhibitor wortmannin (1 microM) inhibited noradrenaline release, this effect was still observed in the presence of polymyxin B. Furthermore ethanol, which inhibits diacylglycerol formation by phospholipase D, had no effect on noradrenaline release. 7. We therefore suggest that during a train of high frequency pulses phospholipase C is activated and this results in the production of diacylglycerol which in turn activates PKC. This enables the neurones to maintain transmitter release at a high level.
Androstadienes↗
The duration of normal visual exposure necessary to prevent form deprivation myopia in chicks.
The aim of this study was to determine the minimum daily period of exposure to normal visual stimulation required to prevent occlusion induced myopia in chicks. Chicks were treated with monocular translucent occlusion in a 12 hr light/12 hr dark cycle. Occluders were removed for 0 (constant occlusion), 15, 20, 30, 40, 60, 75, 90, 120, 150, 240 or 720 (no occlusion) minutes each day for either 2 or 3 weeks. Fellow eyes and the eyes of normal chicks (bilaterally unoccluded) were used as controls. Occlusion-induced myopia and axial elongation were found to decrease significantly (P < 0.01) with increasing daily exposure to normal visual stimulation. Application of a time series equation to the data estimates that 30 and 130 min of normal visual exposure per day reduces myopia by 50 and 95% respectively. This study demonstrated that the regulation of ocular growth is affected strongly by short periods of normal visual stimulation in the presence of long periods of abnormal stimulation.
Animals↗
Trifluoperazine and calmidazolium have multiple actions on the release of noradrenaline from sympathetic nerves of mouse atria.
The aim of this study was to determine whether the calmodulin inhibitors trifluoperazine (TFP) and calmidazolium (CMZ) could decrease the action-potential-evoked release of noradrenaline from mouse isolated atria incubated with [3H]-noradrenaline in support of the hypothesis that calmodulin is involved in neurotransmitter release. TFP (10 microM and 30 microM) significantly enhanced stimulation-induced (S-I) outflow of radioactivity from mouse atria but had no effect at 1.0 microM or 70 microM. TFP (70 microM) also significantly increased the spontaneous outflow of radioactivity. The facilitatory effect of TFP (10 microM) on S-I outflow of radioactivity persisted in either the presence of 3-isobutyl-1-methylxanthine (100 microM) or atropine (0.3 microM) indicating that this effect of TFP was not mediated through either inhibition of phosphodiesterases or through interference with presynaptic muscarinic receptors, respectively. In the presence of phentolamine, the facilitatory effect of TFP (10 microM) on S-I outflow was reduced but there was no effect on S-I outflow at 70 microM. However, in the presence of a combination of both phentolamine (1.0 microM) and the neuronal uptake blocker desipramine (1.0 microM) a significant inhibitory effect of TFP (70 microM) on the S-I outflow of radioactivity was observed, indicating that effects of TFP on presynaptic alpha-adrenoceptors and neuronal uptake had disguised an inhibitory effect on S-I noradrenaline release. Another inhibitor of the Ca(2+)-calmodulin complex, calmidazolium (CMZ, 10 microM) inhibited the S-I outflow of radioactivity but had no effect at 1.0 microM. However, CMZ (10 microM) also induced a concomitant increase in the spontaneous outflow of radioactivity.(ABSTRACT TRUNCATED AT 250 WORDS)
1-Methyl-3-isobutylxanthine↗
Evidence that M1 muscarinic receptors enhance noradrenaline release in mouse atria by activating protein kinase C.
1. The M1 selective muscarinic agonist, McNeil A 343, enhanced the electrically evoked release of noradrenaline from postganglionic sympathetic nerves in mouse atria. This has been found previously to be due to activation of muscarinic receptors of the M1 subtype, probably located on sympathetic nerve terminals. The present study investigated the signal transduction mechanisms involved in the release-enhancing effects of McNeil A 343. The release of noradrenaline from mouse atria was assessed by measuring the electrically-induced (3 Hz, 60 s) outflow of radioactivity from atria which had been pre-incubated with [3H]-noradrenaline. 2. 8-Bromo cyclic AMP in the presence of IBMX was used to enhance maximally S-I noradrenaline release through cyclic AMP-dependent mechanisms. However, the facilitatory effect of McNeil A 343 (10 microM) was not different from the effect in the absence of these drugs, suggesting that McNeil A 343 enhances noradrenaline release independently of the cyclic AMP system. Furthermore, the release-enhancing effect of McNeil A 343 (10 microM) on noradrenaline release was also not altered by the 5-lipoxygenase inhibitor, BW A4C. 3. The facilitatory effect of McNeil A 343 was not altered in the presence of drugs (trifluoperazine, W7, and calmidazolium) which inhibit calmodulin-dependent processes, suggesting that the mechanisms of action of McNeil A 343 does not depend on calmodulin. 4. It was considered likely that the facilitatory effect of McNeil A 343 on noradrenaline release may be due to activation of protein kinase C, since activators of protein kinase C enhance noradrenaline release. The facilitatory effect of McNeil A 343 was abolished by the non-selective protein kinase C inhibitor,K-252a. To investigate further the involvement of protein kinase C, mouse atria were chronically incubated (9-O h) with the protein kinase C activator, 4 beta-phorbol dibutyrate (1.0 microM) in order to down-regulate protein kinase C activity. In protein kinase C-down-regulated atria, the facilitatory effect of McNeil A 343 (30 microM) was abolished. Incubation with 4 alpha-phorbol dibutyrate which does not affect protein kinase C did not reduce the facilitatory effect of McNeil A 343. This provides evidence that activation of protein kinase C is involved in the signal transduction process of McNeil A 343.
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
Effects of selective neurotoxins on eye growth in the young chick.
We have determined the extent of retinal cell damage and eye growth after treatment with different neurotoxins. Day-old chicks received an intraocular injection containing 2, 10, 50, 100 or 200 nmol of kainic acid (KA), an excitotoxic analogue of glutamate. After 21 days, with 2 nmol KA damage was confined to a small proportion of bipolar cells, whereas with 10-200 nmol KA there was dose-dependent damage to amacrine cells, ganglion cells and photoreceptors. There was an increase in eye weight and size of the vitreal chamber with 10 nmol KA or more. In a similar protocol using 5, 50 or 200 nmol quisqualic acid (QUIS), there was massive loss of amacrine cells and slight loss of horizontal cells, and a large increase in the anterior chamber depth. A single dose of 200 nmol N-methyl-D-aspartate lesioned amacrine cells, but did not alter eye size. Thus, excitotoxins which have different retinotoxic effects also have different effects on eye size. In another study, we examined the effects of KA and QUIS on occlusion-induced eye enlargement. Treatment with 200 nmol QUIS alone resulted in increased depth of the anterior chamber. QUIS combined with occlusion for 3 weeks did not interfere with occlusion-induced growth of the vitreal chamber. Therefore, the loss of a large proportion of amacrine cells did not interfere with occlusion-induced growth. KA results in eye growth in its own right, but restricts occlusion-induced growth. These effects are associated with damage to photoreceptors, amacrine and bipolar cells and a small proportion of ganglion cells. Finally, we examined the effects of an intraocular injection of tunicamycin, a purported photoreceptor-specific neurotoxin in amphibia. Tunicamycin (0.1 or 1 mumg/eye) resulted in a flattened anterior chamber but did not affect growth of the vitreal chamber. Tunicamycin inhibited occlusion-induced growth, and treated retinae displayed massive disruption and loss of all cell types apart from a single row of pigmented retinal epithelium. We conclude that (a) normal and occlusion-induced eye growth may have separate mechanisms of action, (b) the vitreous and anterior chambers have different growth mechanisms, and (c) photoreceptors may play a critical role in occlusion-induced growth of the eye.
Animals↗
Excitatory amino acids interfere with normal eye growth in posthatch chick.
This study examines the effects of excitotoxic amino acids on eye growth and retinal morphology. Day old chicks received a single intraocular injection of either 200 nmoles kainic acid (KA), 200 nmoles quisqualic acid (QUIS) or 400 nmoles N-methyl-D,L-aspartate (NMDA). Following survival periods of 7, 14 and 21 days, eyeballs were removed and weighed. Measurements of axial length, equatorial length, anterior chamber depth and corneal diameter were taken. Treatment with KA increased eye weight and equatorial length. Treatment with QUIS increased the anterior chamber depth but decreased the equatorial length. Treatment with NMDA increased anterior chamber depth, but to a lesser extent than QUIS. The effects of QUIS and NMDA could be distinguished from those of KA since the former excitotoxins resulted in a marked increase in anterior chamber depth with no enlargement of vitreal chamber. Changes in eye size were evident by day 7 and were sustained throughout the duration of the experiment. Examination of retinae revealed that KA lesions amacrine cells, bipolar cells, some ganglion cells and photoreceptors. Exposure to QUIS lesions amacrine cells, horizontal cells and causes mild disruption of photoreceptor outer segments. In contrast, NMDA predominantly lesions amacrine cells. The results demonstrate that these neurotoxins have different effects on eye growth, which may be associated with differences in retinal pathology. It is proposed that photoreceptors are ideally suited to play a role in the control of eye growth.
Animals↗