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Biomedical subjects

A M Reynolds

Publications and source records attributed to A M Reynolds.

28 records · Page 2Linked to original sources
PubMed1997

Tachykinins contribute to the acute airways response to allergen in sheep actively sensitized to Ascaris suum.

Tachykinins, found in sensory nerves, have effects in the airways which suggest that they may contribute to the pathogenesis of asthma. We aimed to find evidence for tachykinin involvement in the immediate airway response to allergen in a sheep model of experimental asthma. Twenty-four sheep were actively sensitized to Ascaris suum, then challenged with nebulized Ascaris extract in a dose-response fashion. Change in lung resistance (RL) in response to challenge was measured. Responder sheep (those with an increase in RL of > or = 100% over baseline) that had reproducible responses over three challenges were identified (n = 4 sheep) and a PC100 (number of breaths of extract required to induce a 100% increase in RL) was determined. The effect of the neutral endopeptidase inhibitor phosphoramidon, the NK-1 receptor-specific antagonist CP 96, 345 and capsaicin desensitization on the RL response to Ascaris challenge was then assessed. Administration of phosphoramidon before Ascaris decreased the PC100 to 31 +/- 7% of the PC100 seen with Ascaris alone (P < 0.05), whereas CP 96,345 and capsaicin desensitization increased the PC100 to 285 +/- 41% and 555 +/- 93% respectively (P < 0.05 for both). These findings suggest that endogenous tachykinins are released in response to allergen challenge and that they contribute to the immediate increase in RL.

Allergens↗
PubMed1994

Memory for spatial location as a function of temporal lag in rats: role of hippocampus and medial prefrontal cortex.

Rats with medial prefrontal cortex, hippocampus, or cortical control lesions were tested on an eight-arm radial maze task, in order to examine memory for the temporal order of spatial locations as a function of temporal lag. During the study phase of each trial, rats were allowed to visit each of eight arms once in an order that was randomly selected for that trial. The test phase required the rats to choose which of two arms occurred earlier in the sequence of arms visited during the study phase. The arms selected as test arms varied according to temporal lag (0-6) or the number of arms that occurred between the two test arms in the study phase. The control rats performed at chance at a temporal lag of zero, but their performance was above chance for the remaining lags, improving after the temporal lag exceeded zero. The hippocampal-lesioned rats showed a marked deficit, performing at chance for all lags, with some savings for those items occurring at the end of the list. The medial prefrontal cortex-lesioned rats showed a less severe deficit. The results of these data support the notion that both the hippocampus and the medial prefrontal cortex play significant roles in memory for the temporal order of spatial locations.

Animals↗
PubMed1992

Airway hypocapnia increases microvascular leakage in the guinea pig trachea.

We have previously shown that airway hypocapnia induced bronchoconstriction in the guinea pig lung by releasing tachykinins. To examine whether airway hypocapnia could also cause an increase in airway microvascular leakage, a tracheal segment was isolated in vivo in anesthetized guinea pigs and unidirectionally ventilated (200 ml/min) for 1 h with fully conditioned air (0% CO2) or isocapnic gas (5% CO2). The lungs were ventilated through a distally placed tracheal cannula. Microvascular leakage was quantitated by the injection of Evans blue (EB) and its extraction from the tracheal segment. EB extravasation was increased in tracheae exposed to 0% CO2 (52.3 +/- 2.0 micrograms/g wet tissue) compared with tracheae exposed to 5% CO2 (26.4 +/- 2.9 micrograms/g; p less than 0.05) and to tracheae from spontaneously breathing guinea pigs (25.2 +/- 2.3 micrograms/g; p less than 0.05). Groups of animals in which trachea were unidirectionally ventilated with 0% CO2 were then pretreated with a range of drugs in an attempt to determine the mediators responsible for the microvascular leakage with 0% CO2. Capsaicin and morphine pretreatment did not significantly alter 0% CO2-induced EB extravasation, and phosphoramidon prevented rather than increased extravasation, suggesting that tachykinins did not play a role. The hypocapnia-induced increase in microvascular leakage was, however, prevented by indomethacin pretreatment and significantly attenuated by dazmegrel, a thromboxane synthetase inhibitor. We conclude that airway hypocapnia causes microvascular leakage in the guinea pig trachea and that this effect is mediated by prostaglandins and/or thromboxane.

Animals↗
PubMed1991

The effects of chronic exposure to supraphysiological concentrations of 3, 5, 3' triiodo-L-thyronine (T3) on cultured GC cells.

We have characterized the effects of supraphysiological concentrations of T3 on GC cells, a cultured cell line in which physiologic concentrations of T3 regulate cell growth, protein content, and growth hormone (GH) production. GC cells were exposed to 3 times (1.0 nM) and 80 times (25.0 nM) the physiologic concentration of T3 (0.3 nM) for either 4 d or for greater than 3 months. Both short and prolonged exposure to supranormal T3 concentrations supported maximal cell growth rate and induced significant increases in total protein (P less than 0.025) and GH production (P less than 0.01) per cell when compared to measurements in control GC cells. In addition, exposure to 1.0 nM and 25.0 nM T3 for greater than 3 months enhanced the toxicity of heat shock in a manner similar to previously described effects on GC cells due to T3 exposure of shorter duration. Thus, initial responses to raised T3 concentrations in cultured GC cells persisted without alteration when hormone exposure was prolonged for greater than 3 months.

Animals↗
PubMed1989

Tachykinins mediate hypocapnia-induced bronchoconstriction in guinea pigs.

The aim of this study was to determine whether hypocapnia causes bronchoconstriction by releasing tachykinins (TKs) from C-afferent nerves in airways. Hypocapnia-induced bronchoconstriction (HIBC) was induced in anesthetized vagotomized guina pigs by ventilating lungs with a heated humidified hypocapnic gas mixture for 15 min after sudden circulatory arrest. The intensity of bronchoconstriction was assessed by calculating changes in dynamic compliance and by measuring the relaxation lung volume at the completion of experiments. Visualization of the airways by tantalum bronchography showed constriction of segmental bronchi with relative sparing of more proximal airways. Hypocapnia-induced bronchoconstriction was prevented by prior administration of salbutamol aerosol. Three experimental interventions were used to investigate the role of TKs in HIBC: 1) repeated capsaicin injections to deplete airway sensory nerves of TKs, 2) treatment with phosphoramidon, an inhibitor of enkephalinase, the main enzyme responsible for TK inactivation, and 3) topical airway anesthesia. Capsaicin pretreatment markedly attenuated the hypocapnia-induced changes in dynamic compliance (P less than 0.0005) and relaxation lung volume (P less than 0.0002), whereas phosphoramidon augmented these changes (P less than 0.02, P less than 0.03, respectively). Topical anesthesia of airways with lignocaine postponed the onset of bronchoconstriction, whereas the longer-acting, more lipid-soluble local anesthetic, bupivacaine, almost completely prevented HIBC. We conclude that, in the guinea pig lung, HIBC is mediated by TKs that are released after the activation of bronchial axonal reflexes.

Animals↗
PubMed1988

Prevention of abnormal pulmonary mechanics in the postmortem guinea pig lung.

Severe postmortem bronchoconstriction has been shown previously in guinea pig lungs and linked to pulmonary blood loss during exsanguination (Lai et al., J. Appl. Physiol. 56: 308-314, 1984). To reexamine this phenomenon we measured postmortem airway function in anesthetized open-chest guinea pigs after sudden circulatory arrest. Animals were divided into 4 groups of 10 and ventilated for 15 min postmortem with different gases: 1) room air, 2) conditioned air, 3) dry 5% CO2-21% O2-74% N2, and 4) conditioned 5% CO2-21% O2-74% N2. In room air-ventilated lungs there was a 50% decrease in dynamic compliance (Cdyn) by 15 min and marked gas trapping compared with control lungs. Conditioning the room air did not attenuate these changes, but when 5% CO2 was added to the conditioned postmortem inspirate, gas trapping was eliminated and the fall in Cdyn was almost abolished. Ventilation with a dry 5% CO2 gas mixture at room temperature resulted in a 31% fall in Cdyn at 15 min but no gas trapping. We conclude that marked abnormalities of airway function occur postmortem in room air-ventilated guinea pig lungs in the absence of pulmonary blood loss. The changes are mainly due to airway hypocarbia, a known cause of bronchoconstriction, but a reduction in Cdyn can also occur if there is marked airway cooling and drying. Acute postmortem airway dysfunction can be prevented in the guinea pig by maintaining normal airway gas composition.

Animals↗
PubMed1987

Sodium and bicarbonate fluxes in regenerating rabbit corneal endothelium.

Rabbit corneal endothelia were subjected to a cryoinjury (-70 degrees C for 15 sec) and sodium and bicarbonate fluxes were determined at various times after induction of the endothelial destruction. A complete monolayer of cells was present by 4 days that consisted of large cells that underwent division over the next 16 days. Unidirectional sodium fluxes were unaltered by the transformation from large to normal sized hexagonal cells. Unidirectional bicarbonate fluxes showed an increase in Jendostr coupled with a decrease in the net Jstrendo flux. As the cells became smaller these bicarbonate fluxes returned to normal values. The data indicate that the cell margin/cell size ratio is not related to the flux rates, thus the paracellular pathway increase with healing is not related to the passage of either sodium or bicarbonate. Secondly, the data indicate separate effects on both sodium and bicarbonate, suggesting that transendothelial movement of the ions can be separated and that they are not necessarily linked in passage across the endothelium.

Animals↗