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Biomedical subjects

G M Lees

Publications and source records attributed to G M Lees.

48 records · Page 3Linked to original sources
PubMed1979

Elastin and granulation tissue.

The contraction of granulation tissue is an important factor in wound healing. The tract of an abdominal drainage tube closes at the rate of 1 mm/h once the tube is removed. Specialized myofibroblasts are generally believed to be responsible for this process and the presence of elastin in granulation tissue has been debated for many years. A 3-mm polyethylene tube was inserted through the left lobe of the liver in 41 rats. A tube of granulation tissue formed around the plastic. This granulation tissue was isolated, after periods ranging from 8 to 20 days, by removing the left lobe of the liver and scraping away the surrounding liver tissue. Biochemical assay for elastin revealed that normal hepatic tissue does not contain any detectable amount of elastin. All 41 samples of granulation tissue contained elastin with a mean value of 8.5 X 10(-6) g of elastin per milligram of tissue. Normal rat aorta contains 31.4 X 10(-6) g of elastin per milligram of tissue. These tubes of granulation tissue were histologically normal and the presence of elastin was recognized using elastin stains. The exact role of elastin in granulation tissue is uncertain but this experiment clearly demonstrates its generation and presence there.

Animals↗
PubMed1976

Investigation of occurrence of tolerance to bronchodilator drugs in chronically pretreated guinea-pigs.

1 The actions of sympathomimetic amines on isolated preparations of atria, trachea and ileum were studied in vitro in guinea-pigs, which had been pretreated for 5 or 12 days, by subcutaneous injection, with adrenaline (5 mug/kg), salbutamol (0.5 mug/kg), salbutamol (0.5 mug/kg), methoxamine (250 mug/kg) or saline (0.9% w/V NaCl solution). 2 In the trachea, a decrease in sensitivity (tolerance) to the relaxant effect of adrenaline was induced by pretreatment, for 12 but not for 5 days, with adrenaline. In these animals, cross-tolerance to isoprenaline or salbutamol was not observed. Tolerance to the relaxant actions of adrenaline isoprenaline or salbutamol was not observed after pretreatment with salbutamol. 3 In the trachea, pretreatment with methoxamine or adrenaline for 12 days did not change the sensitivity to the alpha-adrenoceptor-mediated contractor action of methoxamine. 4 In the atria from those guinea-pigs pretreated with adrenaline or salbutamol, there was no reduced sensitivity to the beta-adrenoceptor agonist actions of adrenaline, isoprenaline or salbutamol. In animals pretreated with methoxamine or adrenaline, there was no observable tolerance or cross tolerance to methoxamine with respect to its alpha-adrenoceptor-mediated positive inotropic action in the atria and no unequivocal evidence of a reduced sensitivity to that action of adrenaline. 5 It was confirmed that the twitch-like contractions of the longitudinal muscle of the electrically stimulated ileum were inhibited by sympatomimetic amines acting on alpha- and beta-adrenoceptors. There was no reduced sensitivity to the inhibitory actions of noradrenaline or isoprenaline on the twitch of ileum isolated from animals pretreated with adrenaline, salbutamol or methoxamine for 5 or 12 days. 6 From our results on these three preparations from the same animals, it is concluded that generalizations regarding changes in sensitivity to sympathomimetic amines following their prolonged administration should not be made in any one species.

Animals↗
PubMed1974

Hyperpolarization of rabbit superior cervical ganglion cells due to activity of an electrogenic sodium pump.

1 The mechanisms underlying the hyperpolarization which follows depolarization of rabbit superior cervical ganglion cells by acetylcholine, have been investigated and compared with the mechanisms responsible for the hyperpolarizations induced by orthodromic stimulation of the ganglion.2 The amplitude of the drug-induced hyperpolarization (after-hyperpolarization) was diminished when [Na(+)](0) and the duration of the preceding depolarization were reduced.3 In K(+)-free solutions, the amplitude of the after-hyperpolarization was often diminished and its rate of development was reduced. In 12.5 mM K(+)-Krebs solutions, the amplitude and rate of development of the after-hyperpolarization were increased; the potential was still present when the resting potential was at or close to E(K).4 Ouabain (10 muM) prevented or greatly diminished the after-hyperpolarization. The rates of onset and decay of the after-hyperpolarization were reduced in glucose-free solutions.5 It is, therefore, concluded that the after-hypolarization is due to the activity of an electrogenic sodium pump.6 The positive after-potential associated with the ganglionic action potential was increased in K(+)-free solutions and diminished when the resting potential approached E(K), indicating that it is due to a period of increased K(+) conductance. In the presence of high concentrations of hexamethonium (276 muM), the P wave was not selectively depressed by ouabain and has been shown by other workers to be due to a mechanism not involving an increased potassium conductance. It is concluded, therefore, that the positive after-potential, the P wave and the after-hyperpolarization are due to different mechanisms.

Acetylcholine↗
PubMed1972

Analysis of the mechanism of action of some ganglion-blocking drugs in the rabbit superior cervical ganglion.

1. Mechanisms of action of hexamethonium, mecamylamine and (+)-tubocurarine on the rabbit superior cervical ganglion were investigated by intracellular recording techniques.2. In concentrations up to 1 mM, none of these drugs affected the resting membrane potential nor altered the excitability of the postganglionic neurone to direct or antidromic stimulation.3. Post-tetanic potentiation of the excitatory postsynaptic potential (e.p.s.p.) was inhibited by mecamylamine (10-100 muM) but not affected by either hexamethonium (5-100 muM) or (+)-tubocurarine (10-50 muM).4. The decline in amplitude of successive e.p.s.ps in a train (40 Hz) was not influenced by hexamethonium or (+)-tubocurarine but was greatly exaggerated in the presence of mecamylamine; desensitization of the receptors for acetylcholine was excluded as a possible explanation for this latter finding.5. Mecamylamine depressed the quantal content of e.p.s.ps in a train, with the exception of the first e.p.s.p. which had an increased quantal content.6. Reduction in quantal content was attributed to a substantial fall in the size of the store of quanta of transmitter immediately available for release and to a reduction in the rate of mobilization of acetylcholine into that store; mecamylamine also caused a simultaneous increase in the fractional release.7. Hexamethonium and (+)-tubocurarine had no effect on transmitter release.8. The time-course of presynaptic effects of mecamylamine was similar to the duration of its postsynaptic blocking action.9. It is concluded that inhibition of ganglionic transmission by mecamylamine is due to both presynaptic and postsynaptic inhibitory actions; in contrast, hexamethonium and (+)-tubocurarine reduce transmission solely by their postsynaptic actions.

Animals↗
PubMed1970

Synaptic potentials recorded by the sucrose-gap method from the rabbit superior cervical ganglion.

1. Compound ganglionic potentials evoked by stimulation of the preganglionic nerves to the superior cervical ganglion of the rabbit were recorded by the sucrose-gap method.2. When the distal part of the ganglion was bathed in flowing isotonic sucrose solution or sodium-deficient solutions, ganglionic action potentials were no longer evoked, only large synaptic potentials.3. The compound synaptic potential, which remained unaltered for more than 1 h, originated in a population of cells at the interface between the Krebs and sucrose solutions. Hexamethonium reduced the size but did not alter the time course of the synaptic potential.4. It is suggested that a higher concentration of sodium ions is required for the generation of ganglionic action potentials than for either conduction in the postganglionic axons or production of synaptic potentials.5. When lithium replaced sodium in the solution bathing the distal part of the ganglion, the synaptic potential was greatly reduced in amplitude. Impulse propagation in the postganglionic axons was only slightly impaired when lithium replaced sodium in the solution bathing the axons.6. A quantitative assessment of the potency of the ganglion-blocking drugs nicotine, pentolinium, hexamethonium and pempidine was made by measuring the depression of the synaptic potentials produced by bathing the distal part of the ganglion in flowing isotonic sucrose solution. The concentrations which produced a 50% depression were 8.1 muM nicotine, 26.5 muM pentolinium, 111 muM hexamethonium and 22.2 muM pempidine.

Animals↗
PubMed1968

Resting and action potentials recorded by the sucrose-gap method in the superior cervical ganglion of the rabbit.

1. Evoked ganglionic action potentials and drug-induced changes in resting potential were recorded by the sucrose-gap method. The height of the action potential was 10-20 mV.2. Since the amplitude of the P wave is inversely proportional to the external potassium concentration between 0.5 and 12 mM, the P wave is probably caused by a phase of increased permeability to K(+).3. In the absence of an anticholinesterase, the depolarizing actions of choline and acetylcholine on the ganglion are almost equal, whereas acetylcholine is 2-3 times more potent than choline on the fibres of the internal carotid nerve. In the presence of eserine, acetylcholine induces a depolarization of the ganglion of up to 14 mV, while increase in [K(+)](o) causes a depolarization of up to 55 mV.4. Although the post-ganglionic fibres in the distal pole of the ganglion are depolarized by drugs, for example, acetylcholine, they contribute little to drug-induced potential changes and probably little to evoked action potentials.5. The hyperpolarization which occurs after exposure of the ganglion to acetylcholine is not due to a phase of increased permeability to K(+).

Acetylcholine↗
PubMedDate not supplied

Nutritional effects of surgical and medical treatment for short bowel syndrome.

BACKGROUND: The choice of treatment options in short bowel syndrome (SBS) is hampered by a lack of comparative studies. This study uses a previously validated juvenile pig model of SBS to compare nontreated controls (C), surgical treatment with either proximal colon interposition (CI) or bowel lengthening (BL), with medical treatment with codeine and cimetidine (M). METHODS: Treatment was initiated 6 weeks after resection of 75% of the small bowel, and animals were followed until sacrifice at week 16. Feed intake and weight gain were monitored throughout; in vivo nutrient absorption, in vitro nutrient transport, sodium-glucose cotransporter activity, and intestinal morphology (gross and microscopic) were examined at the end of treatment. RESULTS: BL and M treatments resulted in improved rates of weight gain; this improvement was associated with improved absorption of dietary fat. The treatments did not affect carbohydrate or protein absorption in vivo. In vitro fatty acid absorption was not increased in any group. Active uptake of glucose was increased in the colon interposition group, but phlorizin binding (reflecting sodium glucose cotransporter activity) did not differ between groups. Gross serosal and microscopic mucosal surface areas increased in all groups; however, there were no significant differences between the treatment groups. CONCLUSIONS: These results demonstrate that bowel lengthening and medical treatment improved the rate of weight gain in this model of SBS. This appeared to be due to improvement in the absorption of dietary fat, which was not caused by alterations in in vitro uptake or mucosal surface area, suggesting these treatments have their affects by altering motility or intraluminal digestion. These findings suggest that these treatments are worthy of further study in treating patients (primary pediatric) with SBS.

Animals↗