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Biomedical subjects

K M Ward

Publications and source records attributed to K M Ward.

34 records · Page 2Linked to original sources

Effects of denervation and immobilisation during development upon [3H]ouabain binding by slow- and fast-twitch muscle of the rat.

The effect of innervation and of muscle inactivity upon the normal production of Na+-K+-ATPase sites, assayed by [3H]ouabain binding, in muscle surface membranes has been determined for the rat. In both slow-twitch soleus (SOL) and fast-twitch extensor digitorum longus (EDL) muscles a large increase was found to occur in [3H]ouabain binding per unit weight of muscle over the first 3 weeks of life. Interruptions of development, brought about by fixation of muscles at different lengths at 5 days of age, had no significant effect upon [3H]ouabain binding by EDL. In contrast, fixation led to a decrease in binding in SOL. When fixed in a shortened position profound morphological changes occurred, although these were not apparent when SOL was fixed in a stretched position. Denervation of SOL at 5 days of age significantly reduced the age related increase in the density of [3H]ouabain binding, whilst denervation of EDL had little effect. It was concluded that normal development of SOL is dependent upon innervation and possibly the resulting muscle activity, whereas development of EDL was relatively independent of innervation.

Animals↗

Effect of denervation during development upon membrane potential and intracellular potassium and sodium activities of skeletal muscle of the rat.

Potassium and sodium ion-selective microelectrodes were used in vitro to investigate the effect of denervation of fast-twitch skeletal muscle (extensor digitorum longus) at 5 days of age upon subsequent development of the resting membrane potential. Normally, during the first 3 weeks of life the balance of intracellular potassium and sodium changed to elevate potassium and to lower sodium. These changes were reflected in the development of a more hyperpolarized resting membrane. Periods of denervation delayed, or prevented, the changes in ion activities and membrane hyperpolarization from occurring. The results are compared with those found after denervation of adult skeletal muscle.

Animals↗

Membrane potential and intracellular potassium and sodium activities after denervation of soleus muscles of neonatal rats.

Potassium and sodium ion-selective microelectrodes were used in vitro to investigate the depolarization of slow-twitch skeletal muscle fibers (soleus) following denervation at 5 to 6 days of age. The normal increase in intracellular potassium ion activity and decrease in sodium ion activity which occurs during the first 3 weeks of life were delayed or prevented by denervation. The results are compared with those found after similar periods of denervation of neonatal rat fast-twitch muscle.

Animals↗

Changes in membrane potential and potassium and sodium activities during postnatal development of mouse skeletal muscle.

Dual-channel potassium-selective and single-channel sodium-selective microelectrodes were used to investigate the cause of changes in resting membrane potential of muscle fibers of the mouse during early development. The resting membrane of extensor digitorum longus fibers hyperpolarized during the postnatal period from -41.8 mV at 4 days of age to -76.4 mV at 27 days. During this period intracellular potassium activity increased by 42.1% from 82.5 mM at 8 days to 117.2 mM at 29 days. Intracellular sodium activity was high at 8 days, 23.7 mM, but decreased rapidly to adult values by 27 days when it was 9.98 mM, a 57.9% reduction in sodium activity. The time course of the change in resting membrane potential was different from that of the potassium equilibrium potential calculated from the data. If only potassium and sodium ions were to make significant contributions to the potential, then it was calculated that the permeability ratio PNa:PK would have to change from a value of 0.0659 at 8 days to 0.0227 at 27 days. The results indicated that other factors might be involved in generating the membrane potential inasmuch as, although both intracellular potassium and sodium activities did not change significantly after 27 to 30 days, the membrane potential had not attained adult values at that time. The possibility that increases in muscle activity during the postnatal period might initiate the changes in membrane polarization and intracellular ion activities is discussed together with possible complications in interpretation due to great variations in fiber diameters.

Animals↗

[3H]Ouabain binding in normal and dystrophic mouse skeletal muscles and the effect of age.

The numbers of Na+-K+ ATPase sites in skeletal muscles of normal and dystrophic mice between 3 and 17 months of age have been estimated using [3H]ouabain binding assays. In normal mice, at all ages, slow twitch muscle, soleus (SOL), bound significantly more [3H]ouabain than fast-twitch muscle, extensor digitorum longus (EDL). [3H]Ouabain binding did not alter in either SOL or EDL from normal mice over the age range studied. The numbers of Na+-K+ ATPase sites did alter in muscles taken from dystrophic mice (C57BL/6J dy2J/dy2J). In EDL there was an increase and in SOL a decrease in [3H]ouabain binding. This may be related to a change in muscle fibre metabolism from glycolytic to oxidative or to an altered activity pattern. Increasing age resulted in a progressive reduction in [3H]ouabain binding of both SOL and EDL from dystrophic mice. Part of this reduction may be only apparent and due to an increase in connective tissue composition of dystrophic muscles. A limited study of muscles from neonate dystrophic mice indicated that abnormal [3H]ouabain binding was not present in EDL before two weeks of age.

Age Factors↗

Malonyl CoA inhibition of carnitine palmityltransferase in rat heart mitochondria.

The effects of malonyl CoA on carnitine palmityltransferase I (CPT-I), fatty acid-supported state 3 respiration, and carnitine reversal of palmityl CoA inhibition of state 3 respiration and of the adenine nucleotide translocator, were studied in isolated rat heart mitochondria. Malonyl CoA was a potent competitive inhibitor of CPT-I with an I50 of 0.8 microM. Fasting did not affect CPT-I activity or the I50 value of malonyl CoA. Malonyl CoA inhibited fatty acid-supported respiration and prevented carnitine from reversing the inhibition of the adenine nucleotide translocator by palmityl CoA. These findings suggest that malonyl CoA may affect fatty acid oxidation in the heart.

Acyl Coenzyme A↗

Intracellular activity of sodium in normal and dystrophic skeletal muscle from C57BL/6J mice.

Potassium and sodium ion-selective microelectrodes were used in vitro to investigate the depolarization of skeletal muscle fibers associated with muscular dystrophy. In dystrophy there was a large increase of intracellular Na activity and an associated decrease in K activity in fibers of extensor digitorum longus muscles. Despite this, the recorded membrane potential was very close to the calculated potassium equilibrium potential (Ek) in dystrophic fibers. In contrast, in normal muscle fibers, Em was significantly depolarized with respect to Ek. The data suggest that in dystrophic fibers there is an increase in the relative membrane permeability to potassium over sodium.

Animals↗

Effects of slow frequency electrical stimulation on muscles of dystrophic mice.

The hind leg muscles of dystrophic mice (C57 BL dy2J/dy2J) wer chronically stimulated at 10 Hz for 30 minutes six times a day. After 14 days of such activity a clinical improvement in the use of the stimulated leg was noticed. The twitch and tetanic tensions developed by the stimulated tibialis anterior and extensor digitorum longus muscles were higher than those developed by the control, unstimulated muscles on the contralateral side. Histochemically visualised activity of the oxidative enzyme succinic dehydrogenase was greater in fibres of the stimulated muscles. The stimulated muscles contained more muscle fibres than unstimulated controls. It is concluded that slow frequency activity has a beneficial effect on muscles of dystrophic mice.

Animals↗

Epiglottic abscess: its occurrence and management.

Twenty-six cases of epiglottic abscess from the English literature are reviewed. The condition occurs nearly exclusively in adults and it has a high mortality rate (30 per cent). The lingual surface of the epiglottis is most commonly involved and less than half of the patients present with severe airway obstruction. The management of the condition is dictated by the degree of airway obstruction.

Abscess↗

Jaundice due to erythromycin estolate.

A 43-year-old male developed abdominal pain and jaundice after the administration of erythromycin estolate. The diagnosis was strongly suspected on clinical grounds, but ultimate confirmation depends upon the demonstration of biochemical and morphological alterations after challenge with the drug.

Abdomen↗

A cost accounting of routine sigmoidoscopic examinations.

Proctosigmoidoscopic examinations were performed on 363 patients who had gastrointestinal but no colonic symptoms. Thirty-four, all over the age of 40, were found to have polypoid lesions, 24 of which were adenomatous. Air-contrast barium enemas were utilized to rule out higher lesions in the patients with one or more adenomatous polyps. One early carcinoma of the ascending colon was so discovered. The cost of finding an adenomatous polyp in a patient without colonic symptoms was calculated to be $523.75 and of a carcinoma $12,570.

Accounting↗

Effects of POCA on metabolism and function in the ischemic rat heart.

Sodium 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA) inhibits carnitine palmityltransferase I and fatty acid oxidation. The effects of POCA on cardiac function and on tissue levels of carnitine and coenzyme A esters were studied in the isolated rat heart subjected to 90 minutes of ischemia with and without 15 minutes of reperfusion. The perfusion medium contained 1.2 mM palmitate and 5.5 mM glucose plus or minus 0.5 mM POCA. This compound prevented accumulation of long-chain acylcarnitine and coenzyme A esters during ischemia and significantly improved the recovery of cardiac output after ischemia and reperfusion. Short-chain acylcarnitine levels were increased during ischemia by POCA. No effects were noted on tissue ATP and lactate levels. POCA may protect the ischemic heart by preventing accumulation of these toxic metabolites and by stimulating glucose utilization during ischemia.

Acyl Coenzyme A↗

Neomycin ototoxicity.

A case of oral neomycin ototoxicity is presented, followed by a summary of known cases in the English literature. While it is known that neomycin is concentrated in the inner ear fluids, at the present time the biochemical basis of its ototoxic effect has not been definitively elucidated. High frequency audiometry can aid in the early detection of the onset of neomycin-induced deafness. Dialysis has a limited but useful role in preventing neomycin ototoxicity.

Deafness↗

Aerobic training and diabetic nephropathy in the obese Zucker rat.

The effects of aerobic exercise training on diabetes control and the development of renal microvascular disease were studied in the obese Zucker rat, an animal model of noninsulin dependent diabetes mellitus (NIDDM). Training consisted of 12 weeks of treadmill running, beginning at six weeks of age. Eight trained obese Zucker rats were compared to 15 obese sedentary controls and to 22 sedentary lean nondiseased littermates. Fasting blood glucose, percent of glycated hemoglobin, serum insulin, serum total cholesterol, body weight and kidney weight, creatinine clearance, urine total protein excretion, urine albumin excretion, and morphometric analyses of cortical glomeruli by light and electron microscopy were performed to evaluate metabolic control, renal function, and structure. Training was associated with less albuminuria, less mesangial volume expansion, and less glomerular basement membrane thickening compared to obese sedentary NIDDM animals. These results suggest that exercise training reduces the glomerular ultrastructural lesions and attenuates the albumin excretion rate in this rat model of obesity-related diabetes.

Aerobiosis↗