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Biomedical subjects

M A Lomax

Publications and source records attributed to M A Lomax.

At least 37 records · Page 2Linked to original sources
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

Responses in milk constituents to intravascular administration of two mixtures of amino acids to dairy cows.

Four Holstein-Friesian cows were used to investigate the effects of intravascular infusions of AA mixtures on milk constituents. Cows were in wk 11 to 28 of lactation and were fed a basal concentrate (142 g of CP/kg of DM) and grass silage (149 g of CP/kg of DM) in a 60:40 ratio (percentage of DM). Cows were fed hourly, and feed intake was fixed at 95% of ad libitum intake for each experimental period. Each cow received a 4-d jugular saline infusion, followed by a 5-d jugular infusion of a mixture of AA. Two mixtures of AA were used in a crossover design. The first mixture contained both the essential AA and non-essential AA found in milk protein (total AA); this mixture was infused at 400 g of AA/d. The other mixture represented the essential AA fraction only and was infused at 208 g/d. Infusion of total AA increased milk protein concentration from 32.4 to 35.0 g/kg, and essential AA increased milk protein concentration from 32.5 to 36.9 g/kg; milk protein yield increased by 87 g/d (total AA) and 143 g/d (essential AA). Intravascular administration of AA specifically stimulated milk protein concentration, and the efficiency with which the AA were used was higher than had been previously reported when AA supply was increased either by dietary supplementation or by abomasal infusion.

Amino Acids↗
PubMed1995

The effect of amino acids on the metabolic fate of 15NH4Cl in isolated sheep hepatocytes.

Ruminants characteristically absorb a large proportion of dietary nitrogen across the portal-drained viscera as ammonia nitrogen which is detoxified by conversion to urea in the liver. In theory, ammonia can supply both nitrogen atoms of the urea molecule via mitochondrial (carbamoyl phosphate) and cytoplasmic (aspartate) precursor pathways of the ornithine cycle but the effect of amino acids on the flux of nitrogen from ammonia to each of the two urea nitrogen atoms has not been determined. We report a study designed to determine the distribution of [15N] ammonia between [15N1]urea and [15N2]urea in sheep hepatocytes in response to ammonia concentrations (0.33, 0.67 and 1.00 mM) in the presence or absence of amino acids. In the absence of amino acids, the enrichment of [15N2]urea rose more rapidly during incubations than [15N1]urea and attained enrichments of 66-88% within 5 min of incubation. At the end of 2.5 h of incubation, [15N2]urea represented 60% and 90% of the total urea molecules at low and high ammonia concentrations, respectively. The enrichments of glutamate and aspartate were similar to [15N1]urea in the cells at the end of the incubations, even in the presence of unlabelled amino acids, supporting the concept of mitochondrial ammonia being in equilibrium with cytosolic aspartate formation. In the presence of amino acids basal urea synthesis increased but ammonia uptake and 15NH4Cl conversion to urea was less than in the absence of amino acids. The rate of formation of [15N1]urea was greater in incubations containing amino acids but when ammonia concentration in the media was raised only [15N2]urea flux increased with no change in either [15N1]urea or the unlabelled species. Measurement of media amino acid concentrations after 2.5 h of incubation in the presence of amino acids revealed that arginine, glutamine, glycine and alanine were removed while there was net formation of aspartate, threonine, serine, glutamate, and the branched chain amino acids. However, less than 12% of the 15N transfer appeared in free amino acids. The increases in basal and unlabelled urea synthesis in the presence of amino acids could be numerically accounted as the sum of arginine and glutamine removal from incubations. It is concluded that in sheep hepatocytes 15NH4Cl removal leads to quantitative formation of [15N2]urea, even in the presence of a physiological mixture of amino acids. The increase in the formation of the [15N1]urea in the presence of amino acids can be explained by the preferential utilisation of the amide nitrogen of glutamine for urea synthesis.

Amino Acids↗
PubMed1995

Hepatic detoxification of ammonia in the ovine liver: possible consequences for amino acid catabolism.

The effects of either low (25 mumol/min) or high (235 mumol/min) infusion of NH4Cl into the mesenteric vein for 5 d were determined on O2 consumption plus urea and amino acid transfers across the portal-drained viscera (PDV) and liver of young sheep. Kinetic transfers were followed by use of 15NH4Cl for 10 h on the fifth day with simultaneous infusion of [1-13C]leucine to monitor amino acid oxidation. Neither PDV nor liver blood flow were affected by the additional NH3 loading, although at the higher rate there was a trend for increased liver O2 consumption. NH3-N extraction by the liver accounted for 64-70% of urea-N synthesis and at the lower infusion rate the additional N required could be more than accounted for by hepatic removal of free amino acids. At the higher rate of NH3 administration additional sources of N were apparently required to account fully for urea synthesis. Protein synthesis rates in the PDV and liver were unaffected by NH3 infusion but both whole-body (P < 0.05) and splanchnic tissue leucine oxidation were elevated at the higher rate of administration. Substantial synthesis of [15N]glutamine occurred across the liver, particularly with the greater NH3 supply, and enrichments exceeded considerably those of glutamate. The [15N]urea synthesized was predominantly as the single labelled, i.e. [14N15N], species. These various kinetic data are compatible with the action of ovine hepatic glutamate dehydrogenase (EC 1.4.1.2) in periportal hepatocytes in the direction favouring glutamate deamination. Glutamate synthesis and uptake is probably confined to the perivenous cells which do not synthesize urea.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1993

Hindlimb protein turnover and muscle protein synthesis in lambs: a comparison of techniques.

A combination of arterio-venous difference, kinetic isotope transfer and blood flow rate techniques were used to measure tyrosine metabolism across hindlimb tissues of nine growing lambs (average live weight 36.5 kg) fed on a range of dry matter intakes. Muscle protein synthesis was measured using a continuous infusion technique and compared with simultaneous estimates of hindlimb protein turnover calculated from the values for tyrosine metabolism. When the specific radioactivity (SRA) of tyrosine in the arterial plasma free pool was assumed to be the same as the SRA of tyrosine in the direct precursor pool of protein synthesis, hindlimb protein synthesis (ksav; 3.66 (SEM 0.50) %/d) was significantly (P < 0.001) higher (68%) than muscle protein synthesis (ksp; 2.18 (SEM 0.31) %/d) but was similar to the value for muscle protein synthesis calculated using the homogenate free tyrosine SRA (ksh; 3.35 (SEM 0.42) %/d). Hindlimb and muscle protein synthesis (y) were both significantly related to dry matter intake (chi) (ksav, r2 0.667, P = 0.007; ksh, r2 0.968, P < 0.001) and there was no significant difference between the slopes (P = 0.532) and intercepts (P = 0.945) of the two regression lines. The results demonstrate that hindlimb protein turnover cannot be quantitatively compared with muscle protein synthesis, probably due to high protein metabolic activity in non-muscular tissues within the hindlimb, although similar responses in protein synthetic rate to the level of feed intake were observed between hindlimb and muscle tissues.

Animals↗
PubMed1993

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↗