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Article ; Online: Prenatal cortisol exposure impairs adrenal function but not glucose metabolism in adult sheep.

Davies, K L / Miles, J / Camm, E J / Smith, D J / Barker, P / Taylor, K / Forhead, A J / Fowden, A L

2024 Volume 260, Issue 3

Abstract: Adverse environmental conditions before birth are known to programme adult metabolic and endocrine phenotypes in several species. However, whether increments in fetal cortisol concentrations of the magnitude commonly seen in these conditions can cause ... ...

Abstract	Adverse environmental conditions before birth are known to programme adult metabolic and endocrine phenotypes in several species. However, whether increments in fetal cortisol concentrations of the magnitude commonly seen in these conditions can cause developmental programming remains unknown. Thus, this study investigated the outcome of physiological increases in fetal cortisol concentrations on glucose-insulin dynamics and pituitary-adrenal function in adult sheep. Compared with saline treatment, intravenous fetal cortisol infusion for 5 days in late gestation did not affect birthweight but increased lamb body weight at 1-2 weeks after birth. Adult glucose dynamics, insulin sensitivity and insulin secretion were unaffected by prenatal cortisol overexposure, assessed by glucose tolerance tests, hyperinsulinaemic-euglycaemic clamps and acute insulin administration. In contrast, prenatal cortisol infusion induced adrenal hypo-responsiveness in adulthood with significantly reduced cortisol responses to insulin-induced hypoglycaemia and exogenous adrenocorticotropic hormone (ACTH) administration relative to saline treatment. The area of adrenal cortex expressed as a percentage of the total cross-sectional area of the adult adrenal gland was also lower after prenatal cortisol than saline infusion. In adulthood, basal circulating ACTH but not cortisol concentrations were significantly higher in the cortisol than saline-treated group. The results show that cortisol overexposure before birth programmes pituitary-adrenal development with consequences for adult stress responses. Physiological variations in cortisol concentrations before birth may, therefore, have an important role in determining adult phenotypical diversity and adaptability to environmental challenges.
MeSH term(s)	Female ; Pregnancy ; Animals ; Sheep ; Hydrocortisone/metabolism ; Adrenocorticotropic Hormone/metabolism ; Fetus/metabolism ; Adrenal Glands/metabolism ; Glucose/metabolism ; Insulin/metabolism ; Gestational Age
Chemical Substances	Hydrocortisone (WI4X0X7BPJ) ; Adrenocorticotropic Hormone (9002-60-2) ; Glucose (IY9XDZ35W2) ; Insulin
Language	English
Publishing date	2024-01-29
Publishing country	England
Document type	Journal Article
ZDB-ID	3028-4
ISSN	1479-6805 ; 0022-0795
ISSN (online)	1479-6805
ISSN	0022-0795
DOI	10.1530/JOE-23-0326
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Article ; Online: Glucocorticoid maturation of mitochondrial respiratory capacity in skeletal muscle before birth.

Davies, K L / Camm, E J / Smith, D J / Vaughan, O R / Forhead, A J / Murray, A J / Fowden, A L

The Journal of endocrinology

2021 Volume 251, Issue 1, Page(s) 53–68

Abstract: In adults, glucocorticoids act to match the supply and demand for energy during physiological challenges, partly through actions on tissue mitochondrial oxidative phosphorylation (OXPHOS) capacity. However, little is known about the role of the natural ... ...

Abstract	In adults, glucocorticoids act to match the supply and demand for energy during physiological challenges, partly through actions on tissue mitochondrial oxidative phosphorylation (OXPHOS) capacity. However, little is known about the role of the natural prepartum rise in fetal glucocorticoid concentrations in preparing tissues for the increased postnatal energy demands. This study examined the effect of manipulating cortisol concentrations in fetal sheep during late gestation on mitochondrial OXPHOS capacity of two skeletal muscles with different postnatal locomotive functions. Mitochondrial content, biogenesis markers, respiratory rates and expression of proteins and genes involved in the electron transfer system (ETS) and OXPHOS efficiency were measured in the biceps femoris (BF) and superficial digital flexor (SDF) of fetuses either infused with cortisol before the prepartum rise or adrenalectomised to prevent this increment. Cortisol infusion increased mitochondrial content, biogenesis markers, substrate-specific respiration rates and abundance of ETS complex I and adenine nucleotide translocator (ANT1) in a muscle-specific manner that was more pronounced in the SDF than BF. Adrenalectomy reduced mitochondrial content and expression of PGC1α and ANT1 in both muscles, and ETS complex IV abundance in the SDF near term. Uncoupling protein gene expression was unaffected by cortisol manipulations in both muscles. Gene expression of the myosin heavy chain isoform, MHCIIx, was increased by cortisol infusion and reduced by adrenalectomy in the BF alone. These findings show that cortisol has a muscle-specific role in prepartum maturation of mitochondrial OXPHOS capacity with important implications for the health of neonates born pre-term or after intrauterine glucocorticoid overexposure.
MeSH term(s)	Animals ; Animals, Newborn ; Cell Respiration ; Female ; Fetus/metabolism ; Hydrocortisone/physiology ; Mitochondria, Muscle/metabolism ; Muscle, Skeletal/metabolism ; Myosin Heavy Chains/metabolism ; Organelle Biogenesis ; Oxidative Phosphorylation ; Oxygen Consumption ; Pregnancy ; Sheep
Chemical Substances	Myosin Heavy Chains (EC 3.6.4.1) ; Hydrocortisone (WI4X0X7BPJ)
Language	English
Publishing date	2021-08-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3028-4
ISSN	1479-6805 ; 0022-0795
ISSN (online)	1479-6805
ISSN	0022-0795
DOI	10.1530/JOE-21-0171
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Article ; Online: Clinical ear, nose and throat training as a percentage of the undergraduate medical curriculum.

Davies, K L / Elhassan, H A

Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery

2012 Volume 37, Issue 6, Page(s) 500–501

MeSH term(s)	Curriculum ; Education, Medical, Undergraduate ; Humans ; Otolaryngology/education ; Surveys and Questionnaires ; United Kingdom
Language	English
Publishing date	2012-12
Publishing country	England
Document type	Letter
ZDB-ID	2205891-6
ISSN	1749-4486 ; 1749-4478 ; 0307-7772 ; 1365-2273
ISSN (online)	1749-4486
ISSN	1749-4478 ; 0307-7772 ; 1365-2273
DOI	10.1111/coa.12034
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Article ; Online: Development and thyroid hormone dependence of skeletal muscle mitochondrial function towards birth.

Davies, K L / Camm, E J / Atkinson, E V / Lopez, T / Forhead, A J / Murray, A J / Fowden, A L

The Journal of physiology

2020 Volume 598, Issue 12, Page(s) 2453–2468

Abstract: Key points: Skeletal muscle energy requirements increase at birth but little is known regarding the development of mitochondria that provide most of the cellular energy as ATP. Thyroid hormones are known regulators of adult metabolism and are important ... ...

Abstract	Key points: Skeletal muscle energy requirements increase at birth but little is known regarding the development of mitochondria that provide most of the cellular energy as ATP. Thyroid hormones are known regulators of adult metabolism and are important in driving several aspects of fetal development, including muscle fibre differentiation. Mitochondrial density and the abundance of mitochondrial membrane proteins in skeletal muscle increased during late gestation. However, mitochondrial functional capacity, measured as oxygen consumption rate, increased primarily after birth. Fetal hypothyroidism resulted in significant reductions in mitochondrial function and density in skeletal muscle before birth. Mitochondrial function matures towards birth and is dependent on the presence of thyroid hormones, with potential implications for the health of pre-term and hypothyroid infants. Abstract: Birth is a significant metabolic challenge with exposure to a pro-oxidant environment and the increased energy demands for neonatal survival. This study investigated the development of mitochondrial density and activity in ovine biceps femoris skeletal muscle during the perinatal period and examined the role of thyroid hormones in these processes. Muscle capacity for oxidative phosphorylation increased primarily after birth but was accompanied by prepartum increases in mitochondrial density and the abundance of electron transfer system (ETS) complexes I-IV and ATP-synthase as well as by neonatal upregulation of uncoupling proteins. This temporal disparity between prepartum maturation and neonatal upregulation of mitochondrial oxidative capacity may protect against oxidative stress associated with birth while ensuring energy availability to the neonate. Fetal thyroid hormone deficiency reduced oxidative phosphorylation and prevented the prepartum upregulation of mitochondrial density and ETS proteins in fetal skeletal muscle. Overall, the data show that mitochondrial function matures over the perinatal period and is dependent on thyroid hormones, with potential consequences for neonatal viability and adult metabolic health.
MeSH term(s)	Adult ; Animals ; Female ; Humans ; Mitochondria/metabolism ; Mitochondria, Muscle/metabolism ; Muscle, Skeletal/metabolism ; Oxidative Phosphorylation ; Oxygen Consumption ; Pregnancy ; Sheep ; Thyroid Hormones/metabolism
Chemical Substances	Thyroid Hormones
Language	English
Publishing date	2020-03-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP279194
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Article: The William Houston Gold Medal Prize in the M.Orth. Exam of the Royal College of Surgeons of Edinburgh held in Edinburgh, 2000.

Davies, K L

Journal of orthodontics

2003 Volume 30, Issue 3, Page(s) 183–195

MeSH term(s)	Adolescent ; Awards and Prizes ; Child ; Extraoral Traction Appliances ; Female ; Humans ; Malocclusion, Angle Class II/therapy ; Orthodontics, Corrective/methods ; Palatal Expansion Technique/instrumentation ; Scotland ; Societies, Dental ; Surgery, Oral
Language	English
Publishing date	2003-09
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	2011954-9
ISSN	1465-3125 ; 0301-228X
ISSN	1465-3125 ; 0301-228X
DOI	10.1093/ortho/30.3.183
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Article ; Online: Effects of dietary crude protein and rumen-degradable protein concentrations on urea recycling, nitrogen balance, omasal nutrient flow, and milk production in dairy cows.

Mutsvangwa, T / Davies, K L / McKinnon, J J / Christensen, D A

Journal of dairy science

2016 Volume 99, Issue 8, Page(s) 6298–6310

Abstract: The objective of this study was to determine how interactions between dietary crude protein (CP) and rumen-degradable protein (RDP) concentrations alter urea-nitrogen recycling, nitrogen (N) balance, omasal nutrient flow, and milk production in lactating ...

Abstract	The objective of this study was to determine how interactions between dietary crude protein (CP) and rumen-degradable protein (RDP) concentrations alter urea-nitrogen recycling, nitrogen (N) balance, omasal nutrient flow, and milk production in lactating Holstein cows. Eight multiparous Holstein cows (711±21kg of body weight; 91±17d in milk at the start of the experiment) were used in a replicated 4×4 Latin square design with a 2×2 factorial arrangement of dietary treatments and 29-d experimental periods. Four cows in one Latin square were fitted with ruminal cannulas to allow ruminal and omasal sampling. The dietary treatment factors were CP (14.9 vs. 17.5%; dry matter basis) and RDP (63 vs. 69% of CP) contents. Dietary RDP concentration was manipulated by including unprocessed or micronized canola meal. Diet adaptation (d 1-20) was followed by 8d (d 21-29) of sample and data collection. Continuous intrajugular infusions of [(15)N(15)N]-urea (220mg/d) were conducted for 4d (d 25-29) with concurrent total collections of urine and feces to estimate N balance and whole-body urea kinetics. Proportions of [(15)N(15)N]- and [(14)N(15)N]-urea in urinary urea, and (15)N enrichment in feces were used to calculate urea kinetics. For the low-CP diets, cows fed the high-RDP diet had a greater DM intake compared with those fed the low-RDP diet, but the opposite trend was observed for cows fed the high-CP diets. Dietary treatment had no effect on milk yield. Milk composition and milk component yields were largely unaffected by dietary treatment; however, on the low-CP diets, milk fat yield was greater for cows fed the low-RDP diet compared with those fed the high-RDP diet, but it was unaffected by RDP concentration on the high-CP diets. On the high-CP diets, milk urea nitrogen concentration was greater in cows fed the high-RDP diet compared with those fed the low-RDP diet, but it was unaffected by RDP concentration on the low-CP diets. Ruminal NH3-N concentration tended to be greater in cows fed the high-CP diet compared with those fed the low-CP diet, and it was greater in cows fed the high-RDP diet as compared with those fed the low-RDP diet. Nitrogen intake and both total N and urea-N excretion in urine were greater for cows fed the high-CP diet compared with those fed the low-CP diet. However, N balance and urinary excretion of purine derivatives were unaffected by dietary treatment. Urea-N entry rate (UER) was greater in cows fed the high-CP diet compared with those fed the low-CP diet; however, UER was unaffected by dietary RDP concentration. The proportion of urea-N recycled to the gastrointestinal tract (as a percentage of UER) was greater in cows fed the low-CP diet compared with those fed the high-CP diet. In summary, reducing dietary CP concentration decreased urinary N excretion but had no effect on milk yield, thus resulting in an overall improvement in milk N efficiency.
MeSH term(s)	Animals ; Cattle ; Diet/veterinary ; Dietary Proteins/administration & dosage ; Digestion ; Female ; Lactation ; Milk/metabolism ; Nitrogen/metabolism ; Rumen/metabolism ; Urea/metabolism
Chemical Substances	Dietary Proteins ; Urea (8W8T17847W) ; Nitrogen (N762921K75)
Language	English
Publishing date	2016-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	242499-x
ISSN	1525-3198 ; 0022-0302
ISSN (online)	1525-3198
ISSN	0022-0302
DOI	10.3168/jds.2016-10917
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Article ; Online: A physiological increase in maternal cortisol alters uteroplacental metabolism in the pregnant ewe.

Vaughan, O R / Davies, K L / Ward, J W / de Blasio, M J / Fowden, A L

The Journal of physiology

2016 Volume 594, Issue 21, Page(s) 6407–6418

Abstract: Key points: Fetal nutrient supply is dependent, in part, upon the transport capacity and metabolism of the placenta. The stress hormone, cortisol, alters metabolism in the adult and fetus but it is not known whether cortisol in the pregnant mother ... ...

Abstract	Key points: Fetal nutrient supply is dependent, in part, upon the transport capacity and metabolism of the placenta. The stress hormone, cortisol, alters metabolism in the adult and fetus but it is not known whether cortisol in the pregnant mother affects metabolism of the placenta. In this study, when cortisol concentrations were raised in pregnant sheep by infusion, proportionately more of the glucose taken up by the uterus was consumed by the uteroplacental tissues while less was transferred to the fetus, despite an increased placental glucose transport capacity. Concomitantly, the uteroplacental tissues produced lactate at a greater rate. The results show that maternal cortisol concentrations regulate uteroplacental glycolytic metabolism, producing lactate for use in utero. Prolonged increases in placental lactate production induced by cortisol overexposure may contribute to the adverse effects of maternal stress on fetal wellbeing. Abstract: Fetal nutrition is determined by maternal availability, placental transport and uteroplacental metabolism of carbohydrates. Cortisol affects maternal and fetal metabolism, but whether maternal cortisol concentrations within the physiological range regulate uteroplacental carbohydrate metabolism remains unknown. This study determined the effect of maternal cortisol infusion (1.2 mg kg
MeSH term(s)	Animals ; Blood Glucose/metabolism ; Female ; Glucose Transport Proteins, Facilitative/genetics ; Glucose Transport Proteins, Facilitative/metabolism ; Hydrocortisone/administration & dosage ; Hydrocortisone/blood ; Insulin/blood ; Lactic Acid/blood ; Maternal-Fetal Exchange ; Oxygen/blood ; Placenta/blood supply ; Placenta/metabolism ; Placental Circulation ; Pregnancy ; Sheep
Chemical Substances	Blood Glucose ; Glucose Transport Proteins, Facilitative ; Insulin ; Lactic Acid (33X04XA5AT) ; Oxygen (S88TT14065) ; Hydrocortisone (WI4X0X7BPJ)
Language	English
Publishing date	2016-11-01
Publishing country	England
Document type	Journal Article
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP272301
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Article: Labellar micromorphology of Bifrenariinae Dressler (Orchidaceae).

Davies, K L / Stpiczynska, M

Annals of botany

2006 Volume 98, Issue 6, Page(s) 1215–1231

Abstract: Background and aims: The two closely related subtribes Bifrenariinae Dressler and Maxillariinae Benth. are easily distinguished on morphological grounds. Recently, however, molecular techniques have supported the inclusion of Bifrenariinae within a more ...

Abstract	Background and aims: The two closely related subtribes Bifrenariinae Dressler and Maxillariinae Benth. are easily distinguished on morphological grounds. Recently, however, molecular techniques have supported the inclusion of Bifrenariinae within a more broadly defined Maxillariinae. The present paper describes the diverse labellar micromorphology found amongst representatives of Bifrenariinae (Bifrenaria Lindl., Rudolfiella Hoehne, Teuscheria Garay and Xylobium Lindl.) and compares it with that found in Maxillaria Pabst & Dungs and Mormolyca Fenzl (Maxillariinae). Methods: The labella of 35 specimens representing 22 species of Bifrenariinae were examined by means of light microscopy and scanning electron microscopy and their micromorphology compared with that of Maxillaria sensu stricto and Mormolyca spp. The labellar epidermis of representatives of Bifrenaria, Xylobium and Mormolyca was tested for protein, starch and lipids in order to ascertain whether this tissue is involved in the rewarding of pollinators. Key results and conclusions: The labella of Bifrenaria spp. and Mormolyca spp. are densely pubescent but those of Xylobium, Teuscheria and Rudolfiella are generally papillose. However, whereas the trichomes of Bifrenaria and Mormolyca are unicellular, those found in the other three genera are multicellular. Hitherto, no unicellular trichomes have been described for Maxillaria, although the labella of a number of species secrete a viscid substance or bear moniliform, pseudopollen-producing hairs. Moniliform hairs and secretory material also occur in certain species of Xylobium and Teuscheria and these genera, together with Maxillaria, are thought to be pollinated by stingless bees (Meliponini). Differences in the labellar micromorphology of Bifrenaria and Mormolyca are perhaps related to Euglossine- and/ or bumble bee-mediated pollination and pseudocopulation, respectively. Although Xylobium and Teuscheria share a number of labellar features with Maxillaria sensu stricto, this does not necessarily reflect taxonomic relationships but may be indicative of convergence in response to similar pollinator pressures.
MeSH term(s)	Flowers/anatomy & histology ; Flowers/classification ; Flowers/cytology ; Flowers/ultrastructure ; Orchidaceae/anatomy & histology ; Orchidaceae/classification ; Orchidaceae/cytology ; Orchidaceae/ultrastructure ; Species Specificity
Language	English
Publishing date	2006-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1461328-1
ISSN	1095-8290 ; 0305-7364 ; 0003-4754
ISSN (online)	1095-8290
ISSN	0305-7364 ; 0003-4754
DOI	10.1093/aob/mcl204
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Article ; Online: Early results of a prospective study on the pyrolytic carbon (pyrocarbon) Amandys® for osteoarthritis of the wrist.

Daruwalla, Z J / Davies, K L / Shafighian, A / Gillham, N R

Annals of the Royal College of Surgeons of England

2012 Volume 94, Issue 7, Page(s) 496–501

Abstract: Introduction: The preliminary results of a pyrocarbon interpositional radiocarpal implant in a small cohort of patients were reviewed. As it is currently only a limited release product, we describe to potential users early complications and negative ... ...

Abstract	Introduction: The preliminary results of a pyrocarbon interpositional radiocarpal implant in a small cohort of patients were reviewed. As it is currently only a limited release product, we describe to potential users early complications and negative outcomes. Methods: Patients were assessed using pain levels, ranges of motion, grip strength, type of and time to return to work as well as pre-operative and post-operative DASH (Disabilities of the Arm, Shoulder and Hand) scores. Radiographs were taken and patient satisfaction was recorded. Results: All six patients were contacted. One was not satisfied. Three had reduced motion. None experienced squeaking. There were no immediate or late post-operative complications. There was one early volar displacement of an implant. Conclusions: Although our early results are somewhat encouraging, further and longer studies are warranted before supporting the use of this particular pyrocarbon implant as a primary procedure.
MeSH term(s)	Adult ; Aged ; Arthroplasty, Replacement ; Biocompatible Materials ; Carbon ; Female ; Humans ; Joint Prosthesis ; Male ; Middle Aged ; Osteoarthritis/surgery ; Prospective Studies ; Range of Motion, Articular ; Treatment Outcome ; Wrist Joint/surgery
Chemical Substances	Biocompatible Materials ; pyrolytic carbon ; Carbon (7440-44-0)
Language	English
Publishing date	2012-09-30
Publishing country	England
Document type	Journal Article
ZDB-ID	80044-2
ISSN	1478-7083 ; 0035-8843
ISSN (online)	1478-7083
ISSN	0035-8843
DOI	10.1308/003588412X13373405386655
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Article: Labellar Micromorphology of Bifrenariinae Dressler (Orchidaceae)

DAVIES, K.L / STPICZYŃSKA, M

Annals of botany. 2006 Dec., v. 98, no. 6

2006

Abstract: BACKGROUND: and Aims The two closely related subtribes Bifrenariinae Dressler and Maxillariinae Benth. are easily distinguished on morphological grounds. Recently, however, molecular techniques have supported the inclusion of Bifrenariinae within a more ... ...

Abstract	BACKGROUND: and Aims The two closely related subtribes Bifrenariinae Dressler and Maxillariinae Benth. are easily distinguished on morphological grounds. Recently, however, molecular techniques have supported the inclusion of Bifrenariinae within a more broadly defined Maxillariinae. The present paper describes the diverse labellar micromorphology found amongst representatives of Bifrenariinae (Bifrenaria Lindl., Rudolfiella Hoehne, Teuscheria Garay and Xylobium Lindl.) and compares it with that found in Maxillaria Pabst & Dungs and Mormolyca Fenzl (Maxillariinae). METHODS: The labella of 35 specimens representing 22 species of Bifrenariinae were examined by means of light microscopy and scanning electron microscopy and their micromorphology compared with that of Maxillaria sensu stricto and Mormolyca spp. The labellar epidermis of representatives of Bifrenaria, Xylobium and Mormolyca was tested for protein, starch and lipids in order to ascertain whether this tissue is involved in the rewarding of pollinators. Key Results and Conclusions The labella of Bifrenaria spp. and Mormolyca spp. are densely pubescent but those of Xylobium, Teuscheria and Rudolfiella are generally papillose. However, whereas the trichomes of Bifrenaria and Mormolyca are unicellular, those found in the other three genera are multicellular. Hitherto, no unicellular trichomes have been described for Maxillaria, although the labella of a number of species secrete a viscid substance or bear moniliform, pseudopollen-producing hairs. Moniliform hairs and secretory material also occur in certain species of Xylobium and Teuscheria and these genera, together with Maxillaria, are thought to be pollinated by stingless bees (Meliponini). Differences in the labellar micromorphology of Bifrenaria and Mormolyca are perhaps related to Euglossine- and/ or bumble bee-mediated pollination and pseudocopulation, respectively. Although Xylobium and Teuscheria share a number of labellar features with Maxillaria sensu stricto, this does not necessarily reflect taxonomic relationships but may be indicative of convergence in response to similar pollinator pressures.
Keywords	Orchidaceae ; feces ; light microscopy ; lipids ; microstructure ; pollinating insects ; pollination ; proteins ; scanning electron microscopy ; starch ; trichomes
Language	English
Dates of publication	2006-12
Size	p. 1215-1231.
Publishing place	Oxford University Press
Document type	Article
ZDB-ID	1461328-1
ISSN	1095-8290 ; 0305-7364 ; 0003-4754
ISSN (online)	1095-8290
ISSN	0305-7364 ; 0003-4754
Database	NAL-Catalogue (AGRICOLA)

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