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Biomedical subjects

M J Jackson

Publications and source records attributed to M J Jackson.

At least 199 records · Page 11Linked to original sources

Transport of sodium and chloride across rat gastric mucosa in vitro.

The effects of ion substitution, inhibitors and variations in transmural p.d. on the movements of sodium and chloride across an in vitro preparation of rat gastric mucosa have been studied. The tissue maintained net steady-state transport of sodium in the mucosal-to-serosal direction in the absence of transmural gradients of electrochemical potential. Sodium transport was independent of the presence of chloride, and was abolished by 1 X 10(-5) M-amiloride. The inhibitor produced a decrease in short-circuit current equivalent to the depression of sodium transport, indicating that the sodium transport process was electrogenic. Variations in transmural p.d. showed that the sodium transport process included two components: one that varied with p.d. and one that was independent of it. These findings have been interpreted in terms of a system for sodium transport composed of three components: two rate-limiting entry mechanisms at the apical membrane, one of which can be represented as a conductive channel for sodium diffusion and the other as a neutral process possibly a sodium-hydrogen exchanger, and a voltage-independent pump at the basolateral membrane analogous to the constant-current pump models described in some other epithelia. The tissue maintained a net secretory movement of chloride in the short-circuited condition. The process responsible for net transport of chloride could be resolved into two components: one that was sodium dependent, electrogenic, and abolished by 8 X 10(-3) M-acetazolamide, and one that was independent of the presence of sodium, electrically silent and abolished by 5 X 10(-4) M-SITS (4-acetamido-4'-isothiocyano-2,2'-disulphonic acid stilbene). Both components of the chloride transport process varied with p.d. These findings were interpreted in terms of a system of three components: two entry mechanisms at the basolateral membrane including a coupled sodium-chloride influx process and a chloride-bicarbonate exchanger in parallel, and a rate-limiting conductive channel at the apical membrane. In addition, the studies on the effects of variations in transmural p.d. on chloride fluxes revealed a symmetrical voltage-independent component, dependent on the presence of chloride in the trans compartment, and it was suggested that this component may reflect the presence of a chloride-chloride exchange mechanism.

Acetazolamide↗

Mechanisms maintaining a low-pH microclimate in the intestine.

The presence of an unequilibrated region adjacent to the mucosal surface of the small intestine has long been suggested. Controversy remains as to the characteristics of this region. This study was designed to further define these characteristics. Our studies demonstrated by two independent methods, pH electrode measurement and dye indicator, that a low-pH compartment does exist at the surface of the intestine. The thickness of this microclimate was estimated to be 700 microns, comparable with that described for the unstirred water layer. Maintenance of the low-pH compartment is due to the presence of a mucus coating rather than hydrogen ion secretion. We postulate that the mucus functions as an ampholyte and restricts hydrogen ion movement in its matrix. The acidic microclimate, unstirred water layer, and the mucus coating might in fact represent a common phenomenon.

Animals↗

Inhibition of lipid peroxidation in muscle homogenates by phospholipase A2 inhibitors.

Chloropromazine, mepacrine, tetracaine, dibucaine, chloroquine, and procaine have been shown to inhibit the iron- and ascorbate-induced lipid peroxidation of skeletal-muscle homogenates in vitro. These compounds are known to be inhibitors of phospholipase activity, but they were also found to be effective in blocking free-radical-mediated damage to lipids in denatured homogenates, to linoleate suspensions, and to glutamic acid solutions where phospholipase activity was not a relevant factor. The inhibitory action did not appear to be related to any iron-binding activity of the compounds.

Animals↗

Experimental mouse muscle damage: the importance of external calcium.

The involvement of extracellular calcium in experimental muscle damage has been studied in an isolated mouse soleus muscle preparation. The enzyme efflux and ultrastructural damage seen after excessive contractile activity were markedly reduced when the extracellular calcium was withdrawn. Low extracellular calcium also protected against the large enzyme efflux seen after treatment with low concentrations of detergent. Treatment of the muscle with the calcium ionophore A 23187 caused significant release of enzyme from the muscle. Nifedipine did not prevent the enzyme release after stimulation and although in some circumstances verapamil appeared to have some protective effect this was probably due to a local anaesthetic action on the muscle and not to any specific effect on calcium movement. It is concluded that extracellular calcium is important in mediating at least the two forms of muscle damage studied here.

Animals↗

Zinc homeostasis in man: studies using a new stable isotope-dilution technique.

A new method has been developed for the study of zinc metabolism in man using the stable isotope 67Zn. The technique involves intravenous infusion of the isotope followed by measurements of the plasma and faecal enrichments over a period of days. A procedure for the analysis of Zn isotopes in plasma and faeces is described which requires the separation of Zn from other elements using the chelator dithizone before analysis by thermal-ionization mass spectrometry. The stable isotope technique has been used in conjunction with a metabolic balance study to obtain measurements of Zn absorption and gastrointestinal secretion in a normal subject. Preliminary measurements of the size of the exchangeable pool of Zn have been made as have estimates of the rates of plasma and whole-body Zn turnover. Following an increase in dietary Zn the body appeared to respond in two ways. The gastrointestinal secretion of Zn increased immediately, but only by a relatively small amount. The absorption of Zn initially increased in proportion to the increase in dietary levels but then decreased within 4 d by an amount sufficient to restore Zn balance.

Adult↗

Experimental skeletal muscle damage: the nature of the calcium-activated degenerative processes.

The role of calcium-activated degenerative processes in the efflux of enzyme from experimentally damaged mouse muscle has been studied using an isolated mouse soleus muscle preparation. Inhibition of mitochondrial activity with dinitrophenol or sodium cyanide was found to cause a large efflux of enzyme. This was largely prevented by withdrawal of the extracellular calcium suggesting that mitochondrial calcium overload does not play a major role in the damage leading to enzyme efflux. Treatment of the muscles with a variety of protease inhibitors had no effect on the enzyme efflux from muscles following exhaustive contractile activity indicating that activation of protease activity is not a major factor in the damaging process. Certain inhibitors of phospholipase-A activity (i.e. dibucaine, chlorpromazine and mepacrine) have been found to significantly reduce the enzyme efflux following treatment of the muscles with dinitrophenol, although other phospholipase inhibitors were without effect. It is suggested that the changes in muscle membrane permeability leading to enzyme efflux following experimental muscle damage are probably the result of calcium-mediated activation of phospholipase A leading to changes in membrane phospholipid metabolism.

Animals↗

Weight reduction in boys with muscular dystrophy.

Many children with muscular dystrophy are overweight, and although weight control is pursued in some centres it is unusual to encourage severe dietary restriction for fear that it might lead to accelerated loss of muscle. In this study, two overweight boys with muscular dystrophy were monitored by whole-body nitrogen balance, total body potassium, strength and functional measurements during calorie restriction. Both patients were found to have a transient loss of nitrogen on commencing the low calorie intake: thereafter, weight loss was not found to have any deleterious effect on muscle bulk or function in either patient. It is suggested that controlled weight-reduction in obese children with muscular dystrophy is a safe and practical way of losing excess fat, which can improve mobility and self-esteem, and may possibly effect longevity.

Adolescent↗

Effect of sodium on transport of weak electrolytes across rat jejunum in vitro.

The effects of ion substitution and inhibitors on the transport of two representative weak electrolytes, benzoic acid and amphetamine, across short-circuited rat jejunum in vitro have been studied. The spontaneous asymmetries in the transport of the weak electrolytes were not dependent on the presence of either bicarbonate or chloride in the incubation medium. Net transport of the weak electrolytes was abolished when choline was substituted for sodium in the fluid bathing the mucosal surface of the tissue, but weak electrolyte transport was independent of the presence of sodium on the serosal side. Weak electrolyte transport was inhibited by ouabain and by orthovanadate. The effect of ouabain was abolished when potassium was substituted for sodium in the serosal fluid, and the effect of orthovanadate was potentiated in this condition. It was shown that the ability of the intestinal epithelium to discriminate between the ionized and non-ionized forms of weak electrolytes was not altered when choline was substituted for sodium in the incubation medium, indicating that the effect of sodium was associated with the driving force for weak electrolyte transport. Weak electrolyte transport was not abolished by raising the serosal potassium concentration, suggesting that the transport process was directly related with the function of the sodium pump, rather than correlated with gradients of electrical or chemical potential established as a consequence of pump activity.

Amphetamine↗

Effects of dietary fiber constituents on intestinal morphology and nutrient transport.

Adult male rats were fed for 4 wk on diets containing no addition, 10% fiber (methoxylated pectin or cellulose), or 2% cholestyramine. Weight gain and food intake in the fiber-fed groups were significantly greater than in control or cholestyramine-fed rats. The small intestine was examined for changes in jejunal villus structure and for in vitro transport characteristics by estimation of unidirectional influxes of 3-O-methylglucose (3-O-MG), alpha-aminoisobutyric acid (AIB), and sodium (Na). Feeding of either fiber component resulted in increases in intestinal villus length and width and in a marked increase in the influxes of 3-O-MG and AIB. Influx of Na also increased but less dramatically than the organic solutes. Cholestyramine feeding resulted in shortened villi and increased separation between villi in the jejunum. With this feeding regimen, influxes of 3-O-MG and AIB were increased, but Na influx was not changed. The results show that certain dietary fiber components may modify intestinal architecture and indicate that these structural changes may be correlated with altered functional characteristics.

Animals↗

Sodium transport in Rana pipiens gastric mucosa.

The transport properties of frog gastric mucosa in vitro have been reexamined in conditions analogous to those used in studies on mammalian systems in which net movements of sodium were observed. Net transport of sodium across frog gastric mucosa was not observed to occur when the mucosal surface was bathed with a well-buffered solution of near neutral pH, indicating that failure to demonstrate sodium transport across frog stomach in previous work could not be ascribed to the low pH value of the solution usually used as the mucosal fluid. Addition of 5 X 10(-4) M amphotericin B to the mucosal solution elicited net transport of sodium and an increase in short-circuit current. These findings indicate that sodium transport may contribute to the electrolyte physiology of frog gastric mucosa in some experimental conditions, and may limit the utility of the three-variable model proposed by Hogben.

Amphotericin B↗

Carbonic anhydrase III in Duchenne muscular dystrophy.

Plasma carbonic anhydrase III (CAIII) levels determined by radioimmunoassay have been compared, in detail, with creatine kinase (CK) as indices of Duchenne muscular dystrophy (DMD). CAIII levels were markedly elevated in all patients but variability of levels in a number of individual patients was higher than CK.

Adolescent↗

Vitamin E and skeletal muscle.

Vitamin E deficiency causes a myopathy in a number of animal species but the mechanism of the damage is obscure. The role of vitamin E in protecting skeletal muscle against exercise-induced damage has been investigated using both in situ and in vitro preparations. Muscles from vitamin E-deficient mice and rats were more prone than normal to damage during contractile activity; the tissue rather than the plasma level of the vitamin is probably the more important factor in this respect. Although vitamin E-deficient muscle was found to be more susceptible to peroxidative damage when stressed with iron and ascorbic acid, it was not possible to demonstrate that the damage occurring during contractile activity was mediated by free radicals.

Animals↗

Lipid peroxidation of skeletal muscle: an in vitro study.

The process of lipid peroxidation of skeletal muscle has been examined in vitro by monitoring the autoxidation of skeletal-muscle homogenates. Skeletal-muscle tissue has been shown to have considerable capacity for autoxidation and the process has been found to be initiated by a free-radical-mediated mechanism, critically dependent on the presence of free iron in the homogenate. The initiating radicals have not been firmly identified, but the results suggest that neither superoxide or hydroxyl radicals are involved. An in vitro technique for assessment of the antioxidant capacity of muscle tissue has also been developed which is capable of demonstrating differences between muscle tissues with differing vitamin E contents.

Animals↗