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Biomedical subjects

M E Symonds

Publications and source records attributed to M E Symonds.

At least 91 records · Page 5Linked to original sources

Adipose tissue development during early postnatal life in ewe-reared lambs.

This study examines the precise time course that brown adipose tissue (BAT) takes to adopt the characteristics of white adipose tissue in postnatal lambs. Perirenal adipose tissue was sampled from ewe-reared lambs within 1 h of birth and at 1, 2, 4, 7, 14, 21 and 30 days of age and analysed for the amount of mRNA for uncoupling protein (UCP), the amount and activity of UCP, and protein, mitochondrial protein and lipid content. This was combined with measurements of colonic temperature and jugular venous plasma concentrations of thyroid hormones and insulin-like growth factor-1 (IGF-1). Over the first 4-7 days of age, large quantities of UCP mRNA were associated with a peak in plasma triiodothyronine concentration at 2 days of age followed by a maximal amount and activity of UCP at 4 days and a basal colonic temperature of 39.3 degrees C. Between 7 and 30 days there was a large increase in lipid deposition as the amount and activity of UCP and the amount of UCP mRNA declined to basal values and colonic temperature was maintained at 40 degrees C. A significant positive relationship between perirenal adipose tissue lipid content and plasma IGF-1 concentration was observed throughout the study period. It is concluded that ovine adipose tissue maturation occurs in two distinct phases over the first month of life. The precise time scale of this process could be regulated in part by the lamb's body temperature which determines whether adipose tissue is required for heat production (i.e. BAT) or as an endogenous energy source (i.e. white adipose tissue).

Adipose Tissue↗

Brown adipose tissue and liver development during early postnatal life in hand-reared and ewe-reared lambs.

This study examined the effects of modest changes in ambient temperature in hand-reared lambs (experiment one) and in ewe-reared lambs (experiment two). Lambs were killed at either 8 or 31 days of age and perirenal adipose tissue was identified as being brown adipose tissue (BAT) from measurements of thermogenic activity (i.e. GDP binding to uncoupling protein in isolated mitochondria) or thermogenic capacity (i.e. detection of uncoupling protein by immunoblotting). In addition, type I and II iodothyronine 5' monodeiodonase (5'MDI) activities were assayed in perirenal adipose tissue, plus type I 5'MDI activity in liver. Plasma samples were also taken for measurements of glucose, lactate, insulin, triiodothyronine (T3) and thyroxine (T4) concentrations. In experiment one, lambs were hand-reared at either warm (WR; 25 degrees C) or cool (CR; 10-15 degrees C) ambient temperatures. Mean growth rate over the first 8 days of life in CR lambs was 88 g/day and increased to 128 g/day over the first month of life. Growth rate in WR lambs was constant at 141 g/day. Thermogenic activity of BAT was significantly higher in CR than WR lambs, but total weight and tissue lipid content of perirenal adipose tissue were significantly lower in the CR group. In both WR and CR lambs, the thermogenic activity of BAT fell by an average of 71% between 8 and 31 days. At 31 days of age, uncoupling protein in mitochondria could be detected only by immunoblotting in adipose tissue sampled from CR lambs. There was no effect of ambient temperature on type I or type II 5'MDI activity in BAT or liver; it decreased in adipose but not liver tissue between 8 and 31 days of age. The plasma concentrations of glucose, insulin and T3 tended to decline with age in CR but not in WR lambs. In ewe-reared lambs perirenal adipose tissue weight and tissue lipid content more than doubled between 8 and 31 days of age, but the level of GDP binding decreased from 85 to 5 pmol/mg mitochondrial protein over this period. Liver weight increased by 55% between 8 and 31 days of age, but hepatic 5'MDI activity remained unchanged. The plasma concentrations of T3, T4 and lactate, but not glucose or insulin, increased between 8 and 31 days of age. It is concluded that hand-rearing lambs at a cool ambient temperature significantly delays postnatal development, to the extent that BAT characteristics are retained. Ewe-rearing lambs enhances the rate at which BAT adopts the characteristics of white adipose tissue, and it prevents the postnatal decline in plasma concentrations of thyroid hormones.

Adipose Tissue, Brown↗

Effect of fetal thyroidectomy on brown adipose tissue and thermoregulation in newborn lambs.

The effect of fetal thyroidectomy on thermoregulation in newborn lambs was investigated. Seven of 14 lambs born normally at term were thyroidectomized at Day 127 of gestation. Colonic temperature and oxygen consumption were measured during non-rapid eye movement sleep 6-45 h after birth. All lambs were then killed and perirenal brown adipose tissue was sampled for measurement of thermogenic activity (guanosine diphosphate binding), uncoupling protein and lipid contents. Thyroidectomized lambs tended to have a mean colonic temperature 2.35 degrees C lower (P = 0.067) than controls and two became hypothermic (i.e. colonic temperature < 35 degrees C). Thyroidectomized lambs exhibited lower rates of oxygen consumption (P = 0.05) and an increased incidence of shivering thermogenesis. The perirenal adipose tissue of these lambs had a lower thermogenic activity (P < 0.01), less uncoupling protein (P < 0.01) and higher lipid content (P = 0.072) compared with intact controls. It is concluded that fetal thyroidectomy results in a decreased ability of newborn lambs to utilize nonshivering thermogenesis in brown adipose tissue as well as increasing the incidence of hypothermia. These changes are associated with decreased synthesis of uncoupling protein and functional development of brown adipose tissue in the late gestation fetus.

Adipose Tissue, Brown↗

Effect of maternal glucose infusion on brown adipose tissue and liver development in the neonatal lamb.

The effect of maternal glucose infusion over the final 5-7 days of gestation in under-fed ewes on perirenal brown adipose tissue (BAT) and liver development in lambs over the first month of neonatal life was examined. During glucose infusion, higher maternal plasma concentrations of glucose and thyroid hormones, and lower plasma concentrations of non-esterified fatty acids and 3-hydroxybutyrate were observed, compared with saline-infused controls. These differences were not observed 1-1.5 h before parturition when plasma concentrations of glucose, lactate, cortisol and thyroid hormones all increased in control ewes. Lamb birthweight and liver and BAT weights were similar between groups, but lambs born to glucose-infused ewes had a higher hepatic glycogen content and greater iodothyronine 5'deiodinase activities in liver and BAT. The norepinephrine, epinephrine and dopamine contents were also greater in BAT sampled from lambs born to glucose infused ewes. Three lambs born to glucose-infused ewes failed to survive beyond the second week of life and exhibited abnormally low plasma triiodothyronine concentrations. It is concluded that maternal glucose infusion stimulates development of the fetal sympathetic nervous system during late gestation but this adaptation does not appear to improve postnatal survival.

3-Hydroxybutyric Acid↗

Influence of rearing temperature on lung development following methimazole treatment of postnatal lambs.

This study examines the effect of ambient temperature on lung development over the first month of postnatal life in lambs treated with a drug which inhibits thyroid hormone synthesis (methimazole, 50 mg day-1 (kg body wt-1)). Twin lambs were hand-reared at a fixed level of nutrition in either a warm (WR, 25 degrees C) or cool (CR, 10-15 degrees C) ambient temperature. Plasma thyroid hormone concentrations were significantly (P < 0.05) lower in WR lambs, but there were no differences between WR and CR groups in thyroid gland weight or hepatic iodothyronine 5'-deiodinase activity at 8 or 29 days of age. Lung weights and the ratio of lung weight to O2 consumption were similar in WR and CR groups at 8 days but both were significantly lower (P < 0.01) in CR lambs at 29 days. Lung weight at 29 days was significantly (P = 0.002) correlated with plasma triiodothyronine concentration in CR but not WR lambs, and laryngeal braking of expiratory airflow was observed in three of seven CR lambs but not in WR lambs. Four WR, but no CR, lambs exhibited a rapid deterioration in health or died unexpectedly between 14 and 21 days of age. These WR lambs were characterized by having small lungs and slower growth rates. It is concluded that in WR lambs chronically treated with methimazole, both lung development and the ability of an individual to adapt effectively to methimazole treatment are compromised. In CR lambs, although lung growth may be reduced this does not appear to compromise O2 consumption or health.

Animals↗

Effect of rearing temperature on perirenal adipose tissue development and thermoregulation following methimazole treatment of postnatal lambs.

This study examined the effect of ambient temperature on perirenal adipose tissue development and thermoregulation over the first month of postnatal life in lambs treated with a drug that reduces thyroid hormone synthesis (methimazole; at a dose of 50 mg day-1 (kg body weight)-1). Twin lambs were hand-reared at a fixed level of nutrition in either a warm (WR; 25 degrees C) or cool (CR; 10-15 degrees C) ambient temperature. Oxygen consumption, heart rate and colonic temperature were measured during non-rapid eye movement sleep in different ambient temperatures (6, 15, 25 and 34-36 degrees C) at 7, 14 and 28 days of age. Plasma thyroid hormone concentrations decreased with postnatal age and were higher in CR than in WR lambs. All lambs increased plasma thyroid hormone concentrations and O2 consumption during cold exposure but this was associated with a mean increase in colonic temperature in WR lambs at 7 or 28 days. Colonic temperature increased with the onset of panting at all ages when lambs were exposed to 34-36 degrees C, a response that was greatest at 28 days in CR lambs. An increase in colonic temperature with age was observed in CR but not WR lambs. Heart rate declined with age only in the WR group. At 8 and 29 days there were no significant differences between WR and CR groups in the occurrence of shivering or in the thermogenic activity (i.e. GDP binding to mitochondria) of perirenal adipose tissue. At 29 days WR lambs possessed more adipose tissue with a higher lipid and DNA content. It is concluded that modest changes in rearing temperature can have a large influence on the control of body temperature and thyroid hormone response to methimazole treatment. CR lambs are able to maintain higher plasma thyroid hormone concentrations and exhibit improved thermoregulation compared with WR lambs without any detectable differences in brown adipose tissue function.

Adipose Tissue↗

Endocrine and metabolic adaptation following caesarean section or vaginal delivery.

The endocrine profile (umbilical venous plasma) of three groups of infants was compared. Samples were taken after eight vaginal deliveries, 11 emergency caesarean sections during labour, and 13 elective caesarean sections before labour. Mean umbilical plasma concentrations of thyroxine and triiodothyronine were significantly higher and cortisol concentration were lower after elective caesarean section compared with the two labour groups. Mean umbilical plasma thyroid stimulating hormone (TSH) concentration was significantly lower after vaginal delivery compared with elective caesarean section. These results suggest that labour reduces plasma thyroid hormone concentrations at birth in association with a rise in cortisol. These adaptations may be the stimulus for the subsequent surge in triiodothyronine previously reported to occur over the first few hours after birth in vaginally delivered infants.

Cesarean Section↗

Effect of beta 3-adrenergic agonist (Zeneca D7114) on thermoregulation in near-term lambs delivered by cesarean section.

We investigated the effect of a beta 3-adrenergic agonist, Zeneca D7114, on thermoregulation in near-term lambs delivered by cesarean section. Lambs were delivered into a cool ambient temperature of 15 degrees C, and between 60 and 80 min of life were given an oral dose of Zeneca D7114 (10 mg.kg body weight-1) dissolved in 20 mL of milk, or milk alone. During the first 0.5 h of life colonic temperature decreased in all lambs, and then increased to plateau levels (39.6-40.4 degrees C) after 120-150 min of life, in 19 out of 23 lambs studied. In the remaining lambs, colonic temperature failed to return to normothermic values, plateauing at 34.3 degrees C. All control lambs were observed to shiver throughout the study, but after Zeneca D7114 treatment 7 out of 10 normothermic lambs stopped shivering, and plateau colonic temperature was 0.8 degree C higher. Hypothermic beta 3-agonist-treated lambs had significantly lower rates of heat production, breathing frequency, and plasma triiodothyronine and cortisol concentrations than normothermic lambs. the level of GDP binding and norepinephrine content of brown adipose tissue (BAT) sampled from hypothermic beta 3-agonist-treated lambs was significantly lower than in normothermic lambs. There was no difference in GDP binding in BAT between control and Zeneca D7114-treated groups, but the Hb content was higher in the latter group. It is concluded that administration of Zeneca D7114 to euthyroid lambs enhances their ability to thermoregulate and restore colonic temperature without altering the thermogenic activity of BAT. This response may be mediated by increasing blood flow to BAT and/or an improvement in the animal's thermal efficiency (i.e. decreased heat loss) due to a reduced reliance on shivering thermogenesis.

Adaptation, Physiological↗

Environmental effects on thermoregulation and breathing patterns during early postnatal development in hand-reared lambs.

This study examines the effect of hand-rearing developing lambs in a warm (WR; 25 degrees C) or cool (CR; 10-15 degrees C) ambient temperature on the control of thermoregulation and breathing patterns, when maintained at a fixed level of nutrition over the first month of postnatal life. Measurements were made during non-rapid eye movement sleep whilst lambs were maintained for at least 1 h at warm (28-19 degrees C) and cold (14-5 degrees C) ambient temperatures at 1, 7, 14 and 30 days of age. All lambs were able to maintain normal body temperature, but oxygen consumption was higher in CR lambs at 14 and 30 days of age. At 1 day of age shivering was rarely observed in any lambs, but at 7 and 14 days of age more WR than CR lambs responded to cold exposure via shivering. Plasma concentrations of triiodothyronine were higher at 7 and 14 days of age in CR lambs. Breathing frequencies were similar in WR and CR lambs, and from 7 days of age the incidence of expiratory laryngeal braking was higher in warm compared with cold study temperatures. By 30 days of age the recruitment of this mechanism was greater in CR lambs. Mean growth rate was slower over the first week of postnatal life in CR compared with WR lambs. This difference decreased over the first month of life, as growth rate increased from 83 to 130 g day-1 in the CR group but remained constant at approximately 150 g day-1 in the WR lambs. Total weight of the lungs and heart, but not the liver, were lower at 1 month but not at 1 week of postnatal life in CR lambs. It is concluded that a modest decrease in the ambient temperature in which postnatal lambs are reared, when on a fixed feed intake, alters lung size, the recruitment of laryngeal braking and the control of body temperature.

Animals↗

Effect of ambient temperature during 1st day of life on thermoregulation in lambs delivered by cesarean section.

We examined the effect of delivering near-term twin lambs by cesarean section into a warm (30 degrees C) or cool (15 degrees C) ambient temperature on the control of thermoregulation. Heat production was measured 20-30 h after birth during non-rapid-eye-movement sleep at 29 and 14 degrees C. At 29 degrees C there was no difference in heat production between groups, but at 14 degrees C cool-delivered (CD) lambs exhibited a 62% greater metabolic response. Irrespective of delivery temperature, 15 of the 18 lambs used shivering thermogenesis during cold exposure, indicating a reduction in the ability to use nonshivering thermogenesis in brown adipose tissue (BAT). Mean plasma concentrations of thyroxine and triiodothyronine were 35 and 45% greater, respectively, in CD lambs than in warm-delivered lambs. The level of guanosine 5'-diphosphate binding in BAT was lower than in normally delivered lambs and was not different between CD and warm-delivered lambs. Cesarean section delivery prevents the rise in BAT thermogenic activity, which results in an increased reliance on shivering thermogenesis to maintain colonic temperature. Under these conditions, delivery into a cool environment increases the plasma concentration of thyroid hormones, which benefits the neonate by enabling a greater thermogenic response via shivering.

Adipose Tissue, Brown↗

Effect of the prenatal maternal environment on the control of breathing during non-rapid-eye-movement sleep in the developing lamb.

This study examines the effects of altering the prenatal maternal metabolic and hormonal environment via chronic cold exposure of under-fed ewes on developmental changes in breathing control of developing lambs. Breathing frequency and timing were measured during non rapid-eye-movement (non-REM) sleep in lambs born from either shorn or unshorn ewes after being maintained for at least one hour at warm (28-19 degrees C) and cool (14-5 degrees C) ambient temperatures at 1, 4, 14 and 30 days of age. Breathing frequency and oxygen consumption were significantly higher in 1 day old lambs born from shorn ewes compared with those lambs born from unshorn ewes, at both warm and cool ambient temperatures. In the shorn group breathing frequency decreased between 1 and 4 days of age and continued decreasing upto 30 days of age, during which period inspiratory and to a greater extent expiratory time, lengthened. Laryngeal "braking" of expiratory airflow was observed in more than 50% of lambs born from shorn ewes during non-REM sleep in the warm at 4, 14 and 30 days of age, and in the cold at 14 and 30 days of age. In contrast, lambs born from unshorn ewes showed no change in breathing frequency between 1 and 4 days of age, but a decrease was observed between 4 and 14 days of age, whilst laryngeal "braking" of expiratory airflow was rarely observed at any age.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of maternal cold exposure on brown adipose tissue and thermogenesis in the neonatal lamb.

1. This study examines the effect of chronic cold exposure during pregnancy, induced by winter shearing twin-bearing ewes 4 weeks before predicted lambing date, on O2 consumption and CO2 production during non-rapid-eye-movement (REM) sleep in lambs maintained for at least 1 h at warm (28-18 degrees C) and cold (14-5 degrees C) ambient temperatures at 1, 4, 14 and 30 days of age. This was combined with measurement of the thermogenic activity (GDP binding to uncoupling protein in mitochondrial preparations) of perirenal adipose tissue from lambs immediately after birth and at 33 days of age. 2. Lambs born from shorn (cold-exposed) ewes were 15% heavier (P < 0.01) and possessed 21% (P < 0.01) more perirenal adipose tissue that contained 40% more protein and mitochondrial protein than unshorn (P < 0.05) controls. Total GDP binding in perirenal adipose tissue was 40% greater (P < 0.05) in lambs born from shorn ewes but there was no difference in lipid content of this tissue between the two groups. 3. At 1 day of age, lambs born from shorn ewes exhibited a 16% higher (P < 0.05) rate of O2 consumption (per kilogram bodyweight) at the warm temperature and a 40% greater metabolic response to the cold ambient temperature. All lambs born from shorn ewes responded to cold exposure without shivering (i.e. via non-shivering thermogenesis) whilst shivering was measured in four out of seven lambs in the unshorn group. These differences had disappeared by 4 days of age as a result of a 25% increased (P < 0.01) rate of O2 consumption in the warm in lambs born from unshorn ewes and a 20% decrease (P < 0.05) in the response to the cold in lambs from shorn ewes. Shivering during cold exposure was measured in six out of nine lambs born from shorn ewes indicating a rapid alteration in thermoregulatory responses to cold during the first few days of life. 4. The levels of GDP binding and mitochondrial protein in perirenal adipose tissue fell by one-third in both groups of lambs during the first 33 days of life whereas lipid content either increased or was unchanged. This indicated that brown adipose tissue (BAT) was developing the characteristics of white adipose tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue↗

Thermoregulation and the control of breathing during non-REM sleep in the developing lamb.

This study investigates how metabolic rate, as required for thermoregulation, interacts with breathing control during development of the lamb. Fifteen lambs were studied sequentially at 4, 14, 30, 45 and 55 days of age. During each study they were maintained at ambient temperatures of 5, 10, 15, 20, 25 and 30 degrees C for at least 1 h before measurements were made during N-REM sleep. Basal oxygen consumption fell from 16.1 +/- 0.72 (+/- SEM) to 10.1 +/- 0.47 ml/min per kg between 4 and 55 days of age, while breathing frequencies fell from 52.3 +/- 4.4 to 32.4 +/- 1.6 breaths/min over this period. Ventilation increased as oxygen consumption increased on cooling below thermoneutrality. In 4 days-old lambs this was achieved by an increase in breath amplitude, whilst in older lambs breathing frequency also rose. As breathing frequency fell there was a greater incidence of expiratory laryngeal braking at thermoneutrality associated with lengthened expiratory time. The ambient temperature at which these effects occurred, together with panting thresholds, progressively changed with age as the upper and lower critical temperatures fell and the thermoneutral range widened during development. It is concluded that metabolic rate provides a powerful stimulus to breathing in infant lambs. As the metabolic stimulus decreases with age, basal breathing frequency falls and expiratory laryngeal braking becomes important not only to protect lung volume, but also, through airway mechanosensory reflexes, in regulating breath time. This interaction is also particularly apparent as the metabolic and respiratory requirements alter to meet changes in ambient conditions.

Age Factors↗