Quantitative analysis of axonal transport by using compartmentalized and surface micropatterned culture of neurons.
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Mitochondria, synaptic vesicles, and other cytoplasmic constituents have to travel long distance along the axons from cell bodies to nerve terminals. Interruption of this axonal transport may contribute to many neurodegenerative diseases including Alzheimer's disease (AD). It has been recently shown that exposure of cultured neurons to beta-amyloid (Abeta) resulted in severe impairment of mitochondrial transport. This Letter describes an integrated microfluidic platform that establishes surface patterned and compartmentalized culture of neurons for studying the effect of Abeta on mitochondria trafficking in full length of axons. We have successfully quantified the trafficking of fluorescently labeled mitochondria in distal and proximal axons using image processing. Selective treatment of Abeta in the somal or axonal compartments resulted in considerable decrease in mitochondria movement in a location dependent manner such that mitochondria trafficking slowed down more significantly proximal to the location of Abeta exposure. Furthermore, this result suggests a promising application of microfluidic technology for investigating the dysfunction of axonal transport related to neurodegenerative diseases. (+info)
The action of ketonic prostaglandins on the guinea-pig myometrium.
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1. Prostaglandin E(1) or E(2) has two clearly distinguishable effects on the guinea-pig myometrium in vitro.2. The first of these, the ;direct' effect, is manifested by contraction accompanied by spiking, is readily modified by changes in the concentrations of Mg(2+), Ca(2+) and K(+) in the suspension medium, and does not long outlast the presence of the prostaglandin in the organ-bath. In this respect it resembles the responses to other stimulants.3. The second effect is manifested by ;enhancement' of the responses to non-specific stimulation, whether this be by chemical or electrical means. Enhancement may be demonstrated for up to 20-80 min after the PGE(1) or PGE(2) has been washed out of the organ-bath, and during this time the myometrium shows no consistent changes in electrical activity or in resting mechanical tension that may be associated with the enhancement effect. Enhancement following PGEs is not readily affected by moderate changes in the Mg(2+), Ca(2+) or K(+) concentrations of the suspension medium, and in all these respects it differs markedly from the effects of other stimulants.4. K(+)-depolarized myometrial preparations show feeble direct responses to PGEs, like those to other stimulants. They also show post-PGE enhancement of the responses to other stimulants, but not of the responses to electric field stimulation.5. The empirical method used for measuring the enhancement effect is examined critically.6. The possible mechanisms of the direct and enhancement effects are discussed. It is postulated that they involve actions at two different sites, which may be on two different types of cell but are more likely to co-exist on the same cells. The direct effect is postulated to result from depolarization at the exposed cell membrane, whereas enhancement may result from facilitation of excitation-contraction coupling. (+info)
Renal tubular flow dynamics during angiotensin diuresis in the rat.
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1. Tubular size and lissamine green transit times were measured in rat kidneys undergoing a diuretic response to angiotensin II (0.5 mug/kg per min), and compared with the changes observed during diuresis induced by osmotic diuretics, noradrenaline and chlorothiazide.2. Angiotensin always caused a marked prolongation in proximal and distal tubular transit times; individual distal convolutions were coloured for prolonged periods, and lissamine green appeared in high concentration in distal tubules.3. Marked changes were observed in superficial tubular calibre during a stable diuretic response to angiotensin. Where distal tubular diameter was normal for the rate of urine flow, proximal tubular volume was generally reduced. In a number of experiments, however, distal tubules were markedly dilated, and in these cases proximal tubular volume was also often increased. Angiotensin may therefore be capable of causing a degree of internal hydronephrosis in the rat kidney.4. Prolongation of dye transit times, and the appearance of a concentrated lissamine green bolus in distal tubules, was suggestive of a decreased superficial nephron flow rate, indicating that the diuretic effect of angiotensin may take place only through deeper nephrons. (+info)
The relationship between the level of cholinesterase in plasma and the action of suxamethonium in animals.
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1. The neuromuscular blocking action of suxamethonium, given by intravenous injection, and the effect upon it of iso-OMPA (tetraisopropyl pyrophosphoramide) in doses which produced marked selective inhibition of cholinesterase in blood were studied in anaesthetized rats and cats, and in mice.2. In cats experiments were also carried out in which suxamethonium was given by intravenous infusion until an effect which remained constant with time was achieved. From the degree of neuromuscular block (under equilibrium conditions) obtained with different infusion rates the infusion rate for 50% reduction in twitch tension of the indirectly stimulated soleus and gastrocnemius muscles (IR50) was calculated. The effect on it of raising the suxamethonium hydrolysing capacity of blood and of selectively reducing the level of cholinesterase in blood by various doses of iso-OMPA was then investigated.3. At relevant stages of each experiment cholinesterase activity in blood was determined with butyrylcholine or benzoylcholine and where appropriate with suxamethonium as substrate.4. The results obtained show that in rats and cats the effectiveness of suxamethonium is unrelated to the level of cholinesterase activity in blood and that raising the suxamethonium hydrolysing capacity in the blood up to 22-fold (in cats) only reduces the IR50 by a factor of 1.6.5. The enhancement of the effectiveness of suxamethonium in the three species (2- to 3-fold in rats, 2- to 4-fold in mice and 7- to 8-fold in cats under the conditions used for comparison) which follows the administration of iso-OMPA is attributable to inhibition of cholinesterase in the tissues.6. It is concluded that the results obtained clearly indicate that the species studied do not give information as regards suxamethonium and its metabolism which is applicable to man. (+info)
Fallopian tube surgery for reversal of sterilization.
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Of 16 consecutive cases of previous sterilization treated by tubal surgery fifteen women tested had patent Fallopian tubes. Over 18 months since operation there were four full-term pregnancies and two abortions among 11 patients. At interview with the patient it is important to emphasize that reconstruction of the tubes is a major operation and carries an increased subsequent hazard of ectopic pregnancy. (+info)
Prostaglandin E2 and the bovine sphincter pupillae.
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1. The bovine isolated sphincter pupillae incubated in Krebs solution releases a biologically active substance tentatively identified as prostaglandin E(2).2. The prostaglandin did not appear to be of neural origin or to result merely from tissue degeneration.3. The spontaneous release of prostaglandin E(2)-like material was related to the tone of the sphincter. Output increased as tone was acquired after setting up the tissue and fell when various procedures were used to reduce the tone.4. Low concentrations of E and F-type prostaglandins produced slow, well-sustained contractions of the atonic sphincter, prostaglandin E(2) being the most potent of those tested. The responses to prostaglandin E(2) were antagonized selectively by a prostaglandin antagonist SC-19220 (a dibenzoxazepine derivative) which in higher concentrations caused dose-dependent relaxations of the preparation.5. Prostaglandins did not appear to modulate transmission from nerve to muscle in the sphincter.6. The hypothesis that prostaglandin E(2) might be produced to act as a local hormone causing tonic contraction of the sphincter pupillae is discussed. (+info)