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Notes: Abstract— Squid axonal preparations consisting of the giant axon plus adhering small nerve fibres were incubated for 30 min with phospholipase A (1, 0.2 and 0.025 mg/ml); phospholipase C (10 and 0.5 mg/ml) or lysolecithin (1 and 0.2 mg/ml) followed by another 30 min incubation in normal sea water. The axoplasm and envelope (sheath) of the axonal preparation were then separated and the phospholipids and free amino acids determined. The released amino acids were also measured in the incubation solutions. Compared to phospholipase C, phospholipase A caused a much greater reduction in the free amino acid content of axoplasm and envelope; and a concomitant much greater increase in amino acids released into the incubation solutions, even when phospholipase A was used in concentrations which caused less phospholipid splitting than phospholipase C. Lysolecithin had a much weaker effect than phospholipase A. It is concluded that disruption of hydrophobic binding has a much greater effect on the structure of the non-lipid portion of the axonal membranes than does disruption of hydrophilic (electrostatic) forces of interaction. Our results can be interpreted in terms of the protein-crystal or mosaic models of membrane structure whereas they do not support the unit membrane hypothesis.

Notes: —Levorphanol (10-3 M) reversibly blocked conduction in the giant axon of the squid and axons from the walking legs of spider crab and lobster. Similar concentrations of levallorphan and dextrorphan blocked conduction in the squid giant axon. Under the same experimental condition morphine caused an approximately 40 per cent decrease in spike height. Levorphanol did not affect the resting potential or resistance of the squid axon. Spermidine, spermine and dinitrophenol had little or no direct effect on the action potential nor did they alter the potency of levorphanol. Concentrations of levorphanol as low as 5 × 10-5 M blocked repetitive or spontaneous activity in the squid axon induced by decreasing the divalent cations in the medium. After exposure to tritiated levorphanol, the axoplasm and envelope of the squid axon accumulated up to 500 per cent of the concentration of tritium found in the external medium, dependent on time of exposure, and other variables. At pH 6 the levels of penetration were 33-50% of those found at pH 8, which correlates with our observation that levorphanol is about 33 % as potent in blocking the action potential at pH 6. The penetrability of levorphanol was not affected by spermidine, dinitrophenol or cottonmouth moccasin venom. Levorphanol did not alter the penetration of [C14]acetylcholine nor did it render the squid axon sensitive to it. The block of axonal conduction by compounds of the morphine series is discussed both as to possible mechanisms and significance.

Notes: Abstract— Two membrane fractions were obtained from electric organ tissue of the electric eel by sucrose gradient centrifugation of tissue homogenates. Electron microscopic examination showed that both fractions contained mainly vesicular structures (microsacs). Both the light and heavy fractions had a-bungarotoxin-binding capacity and Na+-K+ ATPase activity, while only the light fraction had AChE activity. The polypeptide patterns of vesicles derived from both the light and heavy fractions were examined by SDS-polyacrylamide gel electrophoresis and found to be very similar. The ratio of protein to phospholipid in the light vesicles was much lower than in the heavy vesicles, but the relative amounts of individual phospholipids in the two fractions were similar.A marked difference in the permeability of the light and heavy vesicles was observed by measuring efflux of both [14C]sucrose and 22Na+, and also by monitoring volume changes induced by changing the osmotic strength of the medium. All three methods showed the heavy vesicles to be much more permeable than the light ones. Only the light vesicles displayed increased sodium efflux in the presence of carbamylcholine.The AChE in the light fraction does not appear to be membrane-bound, but is rather a soluble enzyme, detached from the membrane during homogenization, which migrates on the gradient similarly to that of the light vesicles. This is supported by the fact that the bulk of the AChE is readily removed by washing the vesicles. Moreover, under the conditions employed in our sucrose gradient separations,‘native’14 S + 18 S AChE exists in the form of aggregates which migrate very similarly to the major peak of AChE activity of tissue homogenates.Separated innervated and non-innervated surfaces of isolated electroplax were obtained by microdissection. α-Bungarotoxin-binding capacity was observed only in the innervated membrane. About 80% of the AChE was in the innervated membrane, and about 70% of the Na+-K+ ATPase in the non-innervated membrane.The data presented indicate that the light and heavy vesicle fractions separated by sucrose gradient centrifugation are not derived exclusively from the innervated and non-innervated membranes respectively, as previously suggested by others, but contain membrane fragments from both sides of the electroplax. The separation of two populations on sucrose gradients may be explained both by the differences in permeability and in protein to phospholipid ratios.

Notes: Abstract: Accumulation of intracellular Ca2+ is known to be critically important for the expression of NMDA receptor-mediated glutamate neurotoxicity. We have observed, however, that glutamate can also increase the neuronal intracellular Mg2+ concentration on activation of NMDA receptors. Here, we used conditions that elevate intracellular Mg2+ content independently of Ca2+ to investigate the potential role of Mg2+ in excitotoxicity in rat cortical neurons in vitro. In Ca2+-free solutions in which the Na+ was replaced by N-methyl-d-glucamine or Tris (but not choline), which also contained 9 mM Mg2+, exposure to 100 µM glutamate or 200 µM NMDA for 20 min produced delayed neuronal cell death. Neurotoxicity was correlated to the extracellular Mg2+ concentration and could be blocked by addition of NMDA receptor antagonists during, but not immediately following, agonist exposure. Finally, we observed that rat cortical neurons grown under different serum conditions develop an altered sensitivity to Mg2+-dependent NMDA receptor-mediated toxicity. Thus, the increase in intracellular Mg2+ concentration following NMDA receptor stimulation may be an underestimated component critical for the expression of certain forms of excitotoxic injury.

Notes: Four groups of 20 patients each received either vecuronium or atracurium together with either glycopyrronium or saline, and underwent anaesthesia free of vagolytic drugs, and surgery devoid of vagal activity. Determinations of plasma histamine concentrations were made to examine the possible correlation between these levels and changes in heart rate and blood pressure as well as a possible relationship with skin reactions after the administration of the relaxants. Patients who received vecuronium without the anticholinergic drug, glycopyrronium, showed a greater tendency towards bradycardia (though not statistically significant) than those given atracurium. More cutaneous reactions were observed with patients who received atracurium than in those with vecuronium, but there was no correlation with plasma histamine concentrations of either relaxant group. There was no correlation either between histamine concentrations and heart rate or blood pressure associated with atracurium. The incidence of bradycardia with either relaxant is low if the anaesthetic technique and the surgery are devoid of vagal activity.

Notes: Thymol may accumulate in halothane vaporizers and influence their accuracy. We determined the thymol concentration in residual liquid halothane of 28 vaporizers in regular use. Two halothane samples were brownish, probably due to a long exposure to light and irregular drainage. Irregularly drained vaporizers contained higher thymol concentrations than those drained weekly (p 〈 0.05). The highest individual thymol concentration was 19 times that found in fresh halothane. Halothane vapour concentration deviated most from setting in Fluotec Mark II vaporizers, but this did not correlate with thymol concentrations in halothane liquid. The need for weekly drainage and regular service of halothane vaporizers is stressed.

Notes: The knee-chest position for lumbar spine surgery is favoured because decreased filling of the epidural veins is associated with reduced peroperative bleeding. However, the position may be unfavourable from a circulatory point of view. In the present study, non-invasive assessment of circulation in the lower limbs was performed in 21 unanaesthetised, healthy volunteers who were placed in the surgical knee-chest position. Measurements included blood flow velocity (colour Doppler ultrasonography), oscillotonometric arterial blood pressure from upper and lower limbs and pulse oximetry from a toe. There was a statistically significant reduction in the posterior tibial artery flow velocity, maximally 31.6%, when the subject was moved from the prone to the knee-chest position. An enlargement of the trunk-femoral angle at the hip did not improve arterial flow. In 10 of the 21 volunteers, no flow in the posterior tibial vein was detected in the knee-chest position. In spite of the deteriorated blood flow, pulse oximetry indicated sufficient capillary flow in the very periphery of the lower limb. The change from prone to knee-chest position resulted in an increase in arterial blood pressure of the upper limb; the increase in diastolic arterial pressure was statistically significant (p 〈 0.001). It is concluded that the surgical knee-chest position involves deterioration of both the arterial and venous flow of the lower limbs. This should be considered in patients undergoing surgery in this position and, in particular, in those at risk of developing cardiovascular complications.

Notes: In a double-blind, randomised study of patients scheduled for minor hand surgery 0.5% 2-chloroprocaine (n = 30) and 0.5% prilocaine (n = 30) in a volume of 40 ml were compared for intravenous regional anaesthesia. The onset of sensory and motor block and recovery of sensory block were determined, and the occurrence of side-effects was noted. Twenty-four patients in the 2-chloroprocaine group and 17 in the prilocaine group developed complete sensory block by 15 min after injection (p 〈 0.05). Complete recovery of sensation was faster after prilocaine (7.1 min) than 2-chloroprocaine (9.8 min) (p〈0.01). Venous irritation and/or urticaria after tourniquet release was observed on 10 occasions in those receiving 2-chloroprocaine and twice in those receiving prilocaine. An increase in heart rate of 〉 20% above control values occurred in three patients, all of whom had been given 2-chloroprocaine. Clinically, local anaesthetic properties of 0.5% 2-chloroprocaine and prilocaine were similar, but there were more side-effects with the former drug.

Notes: Propofol 2.5 mg/kg was compared with thiopentone 5 mg/kg as an induction agent for elective Caesarean section. Thirty-two healthy women with cephalopelvic disproportion were included in an open randomised study. The placental transfer of propofol was also studied in 10 other mothers given a single dose of 2.5 mg/kg. The induction characteristics and haemodynamic response to propofol and thiopentone were similar. Side effects were rare with both agents, but propofol caused more discomfort on injection compared to thiopentone. Recovery times were shorter after propofol as evaluated by time to orientation, recovery scoring after anaesthesia and measurements with the Maddox wing. Rapid placental transfer and significant fetal uptake were detected for propofol. There was no significant neonatal depression as assessed by Apgar scores and blood gas analyses. Propofol appears to be a suitable alternative to thiopentone as an induction agent for anaesthesia in elective Caesarean section.

Notes: The antipyrine (phenazone) half-life was determined in 20 surgical patients to discover whether there are changes in hepatic metabolic rate during or immediately after anasthesia compared with the pre-anasthetic rate. Nine patients received enflurane (mean duration 8.6, SD 2.0 hours) and six patients had a balanced anasthetic without enflurane (duration 4.4, SD 3.3 hours). A further five patients received a spinal anasthetic with bupivacaine. The changes in antipyrine half-life were inconsistent, and there was no evidence of competitive metabolic inhibition, by general anasthesia. Antipyrine half-lives did not correlate with serum fluoride levels or urinary fluoride excretion in the case of enflurane. The mean serum inorganic fluoride concentrution rose to 29 μmol/litre, and two patients had potentially nephrotoxic concentrations (64 and 50 μmol/litre) after 8 hours of exposure to enflurane though without any evident harmful effects.