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Biomedical subjects

K D Cairncross

Publications and source records attributed to K D Cairncross.

At least 19 recordsLinked to original sources

The effect of neonatal pinealectomy on the inhibitory actions of food restriction on vaginal opening and collagen aging in the rat.

Long-term food restriction is known to inhibit development and aging in the rat. These actions may be mediated by the pineal hormone, melatonin, whose secretion is increased by food restriction. This mechanism was investigated by studying the effects of pinealectomy in ad libitum fed and food restricted rats of both sexes living under normal conditions of temperature (23 degrees C) and lighting 12 h light:12 h dark cycle) over a period of 400 days. Pinealectomies were performed at the age of 5 days. Pinealectomy did not affect the amount of food eaten per day. Vaginal opening occurred at age 35 days in ad libitum fed female rats and was delayed to 49 days (P < 0.001) in rats whose food intake was restricted by 35%, but only to 41 days (P < 0.001) if food restricted (FR) rats were pinealectomized (Px). The inhibitory effect of food restriction on body growth and tail tendon collagen fibre aging was the same in both intact and pinealectomized rats. At the conclusion of the study in middle age at 400 days, plasma melatonin levels 4 h into the dark cycle were higher in food restricted than in ad libitum fed rats (P = 0.015). This study provides evidence for a role of the pineal in mediating the inhibitory action of food restriction on vaginal opening, but not on body growth or collagen aging in tail tendon up to middle age.

Aging↗

Preliminary evidence of a synergistic alpha 1- and beta 1-adrenoceptor regulation of rat pineal hydroxyindole-O-methyltransferase.

The activity of serotonin N-acetyltransferase in the rat pineal is regulated through a synergistic action of norepinephrine on alpha 1- and beta 1-adrenoceptors. Rat pineal hydroxyindole-O-methyltransferase (HIOMT) activity is also responsive to the beta 1-adrenoceptor, while melatonin synthesis and indoleamine release in certain species is apparently under alpha 1-adrenoceptor control. The present study reports that the simultaneous administration of doxazosin (a selective alpha 1-adrenergic antagonist) and metoprolol (a selective beta 1-adrenergic antagonist) reduces peak HIOMT activity significantly more than either agent alone, indicating that rat pineal HIOMT is also subject to synergistic alpha 1- and beta 1-adrenergic regulation. The relationship between alpha 1-adrenoceptor stimulation, serotonin release, and HIOMT activity is considered, following the observation that nocturnal HIOMT activity is elevated in serotonin-depleted pineal glands.

Acetylserotonin O-Methyltransferase↗

A distinct diurnal rhythm in hydroxyindole-O-methyltransferase (HIOMT) activity in the male albino rat.

Pineal hydroxyindole-O-methyltransferase (HIOMT) has been reported to show a diurnal rhythm activity in the rat, although this is not fully confirmed. The present study reexamines this issue and reports a distinct diurnal rhythm in rat pineal HIOMT. Peak enzyme activity occurs 5 hr after the onset of darkness, followed by two lesser bursts of activity preceding each change in the photoperiod. The approximately 18-fold increase in methylating capacity at night represents the greatest variation in HIOMT activity thus far reported in the rat and may be attributed to the age, weight, and housing regimen of the animals used.

Acetylserotonin O-Methyltransferase↗

The use of hypothermia in surgical pinealectomy of the neonate rat.

A technique is described in which rat pups (5-7 days old) are induced into a state of suspended animation by placing them in the freezing compartment of a refrigerator at -20 degrees C for 8-10 minutes. This induces cessation of respiration and heart beat for 12-15 minutes. Surgical pinealectomy is undertaken during this period. Postoperation the animal is gradually warmed and restored to its dam. The effectiveness of pinealectomy was checked after some 400 days by measurement of plasma dark cycle melatonin levels using radioimmune assay. The method is reliable, robust and the results predictable, no melatonin being detectable 400 days after surgery.

Animals↗

Investigation of circadian rhythms for pineal 5-hydroxytryptophol and other indoles in the rat.

5-hydroxytryptophol (5HTL) occurs in the pineal gland of the rat at levels comparable to those of melatonin, yet few studies have been conducted to investigate 5HTL as a potential alternative pineal hormone. In this study the pineals of 90-day-old male Sprague Dawley rats have been assayed by high performance liquid chromatography coupled with electrochemical detection. Significant (P less than .0001) circadian variation was measured in 5HTL levels, and a fivefold plateau elevation occurred during the middle of the light period. By comparison with the timing of the variations in N-acetyl serotonin and melatonin levels, it is suggested that 5HTL may not be regulated by simple competition with N-acetyl transferase for the common substrate 5HT but may, in fact, be regulated independently. Literature supporting such a suggestion, and a model incorporating it, are presented for discussion.

Animals↗

Pineal indoles: significance and measurement.

Despite intensive investigation, particularly over the past fifteen years, many aspects of pineal function with respect to mammalian physiology remain obscure. Much of this work is reviewed and particular attention focussed on indole metabolism within the pineal gland. Emphasis is placed on the development of new analytical techniques with special reference to high performance liquid chromatography coupled with electrochemical detection. The growth in knowledge regarding pineal indole synthesis which can be attributed to the use of this technique is discussed. The possibility that pineal indoles other than melatonin may function as hormones or neuromodulators is considered. A functional role for 5-hydroxytryptophol as a neuromodulator, possibly associated with diffuse neuroendocrine function (amine precursor, uptake and decarboxylation, APUD) is suggested.

Animals↗

Maternal and larval effects of photoperiod on the induction of larval diapause in two species of fly, Calliphora vicina and Lucilia sericata.

The induction of larval diapause in the blowflies Calliphora vicina and Lucilia sericata was studied in relation to maternal and/or larval exposure to photoperiod. In C. vicina, maternal experience of short daylength was shown to be more important than larval exposure, although diapause was only observed when the larval rearing temperature was below 15 degrees C. The critical daylength was between 12 and 15 h per day. Recovery from diapause was temperature- but not photoperiod-dependent. Some evidence was obtained, however, to suggest that the rate of recovery was more rapid among larvae from short-day mothers which were bred in pre-diapause conditions of long days. By transferring adult flies from short days into darkness several days before oviposition, it was shown that the important photoperiodic effects were truly maternal. In L. sericata, larval sensitivity to photoperiod was also demonstrated, short days inducing a protracted rate of pupariation. 'Waves' of pupariation in short-day cultures indicated intrinsic differences in diapause intensity. The critical day-length for larval sensitivity was close to 14 h per day. It is suggested that the maternal effects of photoperiod on larval diapause probably involve an unknown maternal factor which is incorporated into the developing oocytes during short-day exposure.

Animals↗

The effect of sulfinpyrazone on morphological changes in the coronary vasculature induced by prolonged unpredictable stress in the rat.

It was confirmed that prolonged unpredictable stress in the rat induces morphological change in the coronary microcirculation. These changes include dilation in venules, deposits staining positive with PAS in the venules due to platelet aggregation and a breakdown of the endothelial lining in arterioles. Sulfinpyrazone is reported to prevent platelet agglutination, and shows effectiveness in the clinic in preventing re-infarction following infarction. Accordingly rats were exposed to the stress regimen for 50 days, and groups were treated with sulfinpyrazone, either prophylactically (receive drug for 50 days) or therapeutically (receive drug Day 30 to Day 50). The morphology of the hearts of treated animals were compared with those of placebo treated controls. It was demonstrated that therapeutic sulfinpyrazone did not prevent (p less than 0.01), but reduced the incidence of morphological change in the coronary microcirculation. Prophylactic sulfinpyrazone had a distinct protective effect (p less than 0.001). It was demonstrated that the plasma corticosterone levels in both drug groups did not fall to the level found in control groups. The results are discussed in terms of a glucocorticoid-sulfinpyrazone interaction preventing prostaglandin release which will prevent platelet aggregation. It is possible that the interaction relates to maintaining the integrity of the microcirculatory endothelial cells, thus preventing the local release of inflammatory substances.

Animals↗

The action of nicotine on the pituitary-adrenal cortical axis.

Nicotine was found to raise dramatically plasma corticosterone levels in a dose-dependent manner. Plasma corticosterone time course for the 100 microgram/kg dose of nicotine produced an initial increase in corticosterone elevation which did not return towards control levels until after 30 min. The 200 and 500 microgram/kg doses, however, indicated a biphasic response for nicotine-induced steroid secretion. The first steroid peak occurred 1-15 min after nicotine administration and was followed by a greater elevation at 20 min. Plasma nicotine levels did not show the same biphasic pattern. The nicotine-induced plasma steroid elevation was completely abolished by hypophysectomy, indicating that the response to nicotine must be mediated through ACTH release from the anterior pituitary. The administration of exogenous ACTH to rats pretreated with betamethasone was found to result in a biphasic plasma steroid elevation similar to that seen after injection of 200 microgram/kg nicotine. It was postulated that this may reflect a differential response of the adrenal cortex to a single ACTH outflow.

Adrenocorticotropic Hormone↗

Plasma thyroid hormone and glucocorticosteroid concentrations in the male rat following prolonged exposure to stress.

Exposure of male CSF rats to a signalled unpredictable 60-day stress regimen induced a significant elevation in circulating triiodothyronine (T3) concentration above the control for the first 20 days of stress before the rate of secretion returned to normal. On the other hand, circulating thyroxine (T4) concentration fell significantly below the control value for the first 5 days of stress before the normal rate of secretion was reached in 10 days. A histological study of the thyroid gland revealed no change in activity among any of the control and stressed groups. At the same time this regimen also induced an initial extreme corticosterone elevation which was maintained for the first 5 days of stress and thereafter gradually fell to re-establish a new level by 40 days with no further change up to 60 days of stress. The possible physiological significance of the marked elevation in T3/T4 ratio as a result of stress is discussed, in particular with relation to higher glucocorticoid secretion.

Animals↗

Changes in the coronary vascular system following prolonged exposure to stress.

Hearts of stressed rats showed marked changes in the coronary vasculature. It was suggested that such morphological changes could be explained on the basis of an increased coronary vascular permeability. Endogenous inflammatory substances could induce swelling of the endothelial cells and cause separation of the neighbouring cells from one another, thus allowing the passage of lipid molecules through the endothelial lining. In order to gain supportive evidence for the above hypotheses an electron microscope study was undertaken. The presence of junctional gaps in the endothelial lining of the coronary vascular system was observed following prolonged stress, as well as platelet aggregation. The use of lipid staining of frozen sections indicated the presence of large lipid deposits in the arteriole walls, corresponding to vacuoles seen previously. It would appear therefore, that prolonged exposure to stress may result in pathological changes in the myocardium associated with changes in the vascular endothelial permeability, and platelet aggregation. Pathological changes induced in this way, however, should be inhibitd by high glucocorticoid levels and should not be manifested until adaptation of the steroid response to stress has occurred. Measurement of plasma glucocorticoid levels over the period of prolonged stress shows a good correlation between the adaptation of the steroid response and the onset of a progressive degeneration of the coronary vascular system.

Animals↗

Ultrastructural changes in the adenohypophysis, adrenal gland activity, and desynchronization of the oestrous cycle following unpredictable stress in the rat.

An ultrastructural study of the adenohypophysis, after exposure of female Wistar rats to a signalled unpredictable 5- and 15-day stress regimen, is described. Cellular activity of the adenohypophysis correlated well with the circulating levels of corticosterone. Intense secretory activity was observed in all tropic cell types at 5 and 15 days although the observed differences generally were greater in the 5-day stressed group. It was observed that the oestrous cycles of 40 and 100% of the rats became desynchronized over the 5- and 15-day stress period respectively.

Animals↗