M. G. Gnanalingham

Ontogeny and nutritional programming of uncoupling protein-2 and glucocorticoid receptor mRNA in the ovine lung.

This study investigated the developmental and nutritional programming of uncoupling protein‐2 (UCP2), glucocorticoid receptor (GR) and 11β‐hydroxysteroid dehydrogenase type 1 (11βHSD1) mRNA in the sheep lung from the time of uterine attachment to 6 months of age. The effect of maternal nutrient restriction on lung development was determined in early to mid gestation (i.e. 28–80 days gestation, period of maximal placental growth, and embryonic and pseudoglandular stages of fetal lung development) and late gestation (i.e. 110–147 days gestation, period of maximal fetal growth, and canalicular and saccular stages of fetal lung development). Fetal lungs were sampled at 80 and 140 days (term ∼148 days) gestation, and sheep lungs at 1, 7, 30 days and 6 months. GR and 11βHSD1 mRNA were maximal at 140 days gestation, whereas UCP2 mRNA peaked at 1 day of age and then declined with postnatal age. Maternal nutrient restriction in both early‐to‐mid and late gestation had no effect on lung weight, but increased UCP2, GR and 11βHSD1 mRNA abundance at every sampling age. These findings suggest that the developmental ontogeny of UCP2 mRNA in the ovine lung is under local glucocorticoid hormone action and that maternal nutrient restriction has long‐term consequences for UCP2 and GR mRNA abundance in the lung irrespective of its timing.

Increased uncoupling protein-2 mRNA abundance and glucocorticoid action in adipose tissue in the sheep fetus during late gestation is dependent on plasma cortisol and triiodothyronine

The endocrine regulation of uncoupling protein‐2 (UCP2), an inner mitochondrial protein, in fetal adipose tissue remains unclear. The present study aimed to determine if fetal plasma cortisol and triiodothyronine (T3) influenced the mRNA abundance of UCP2, glucocorticoid receptor (GR) and 11β‐hydroxysteroid dehydrogenase type 1 (11βHSD1) and 2 (11βHSD2) in fetal adipose tissue in the sheep during late gestation. Perirenal–abdominal adipose tissue was sampled from ovine fetuses to which either cortisol (2–3 mg kg−1 day−1) or saline was infused for 5 days up to 127–130 days gestation, or near term fetuses (i.e. 142–145 days gestation) that were either adrenalectomised (AX) or remained intact. Fetal plasma cortisol and T3 concentrations were higher in the cortisol infused animals and lower in AX fetuses compared with their corresponding control group, and increased with gestational age. UCP2 and GR mRNA abundance were significantly lower in AX fetuses compared with age‐matched controls, and increased with gestational age and by cortisol infusion. Glucocorticoid action in fetal adipose tissue was augmented by AX and suppressed by cortisol infusion, the latter also preventing the gestational increase in 11βHSD1 mRNA and decrease in 11βHSD2 mRNA. When all treatment groups were combined, both fetal plasma cortisol and T3 concentrations were positively correlated with UCP2, GR and 11βHSD2 mRNA abundance, but negatively correlated with 11βHSD1 mRNA abundance. In conclusion, plasma cortisol and T3 are both required for the late gestation rise in UCP2 mRNA and differentially regulate glucocorticoid action in fetal adipose tissue in the sheep during late gestation.

Maternal dexamethasone administration and the maturation of perirenal adipose tissue of the neonatal sheep

Maternal dexamethasone administration promotes fetal maturation such that thermoregulation is improved following premature delivery and is thus comparable with a full term birth. In the present study we determined the impact of dexamethasone on both the mothers’ metabolic status together with adipose tissue function in the newborn. Glucocorticoid action, adipokine gene expression and mitochondrial protein abundance were measured in perirenal adipose tissue of neonatal sheep that were born into either a warm (30oC) or cool (15oC) ambient temperature at 140 days of gestation (dGA; term ~147 dGA), either two days after maternal dexamethasone administration, or at 146 dGA for controls. Dexamethasone administration resulted in a reduction in maternal food intake in conjunction with raised plasma cortisol and free triiodothyronine. In offspring of dexamethasone administered mothers, plasma cortisol was lower and non-esterified fatty acids (NEFA) higher than controls. Glucocorticoid receptor (GR), 11β-hydroxysteroid dehydrogenase (11β-HSD1), interleukin-6 and uncoupling protein (UCP)1 and 2 mRNA together with voltage dependent anion channel, cytochrome c protein and UCP1 abundance were all increased by dexamethasone administration and being born into a cool ambient temperature. Gene expression of tumor necrosis factor α, adiponectin and peroxisome proliferator-activated receptor transcription factor γ were unaffected by dexamethasone. The abundance of mRNA for the GR, 11β-HSD1, UCP1 and 2 mRNA together with each protein were positively correlated to plasma NEFA and negatively correlated to plasma cortisol. In conclusion, despite reduced maternal food intake dexamethasone promotes maturation of glucocorticoid action and mitochondrial protein abundance in the newborn, an adaptation dependent on delivery temperature.

The availability and accessibility of basic paediatric resuscitation equipment in primary healthcare centres: cause for concern?

Background: Paediatric emergencies in primary healthcare centres are serious events that occur more commonly than envisaged. However, at present, these centres appear to lack the training and equipment to manage common paediatric emergencies. Aim: To determine the availability and accessibility of basic resuscitation equipment in primary healthcare centres. Methods: A questionnaire survey of 27 primary healthcare centres within the Nottingham City region determined the availability and accessibility of basic paediatric resuscitation equipment and algorithms. Results: No practice had all 21 basic resuscitation items, with 59% of practices having ≤10 of these items. Only 11% of practices had all seven basic airway and breathing resuscitation items, with 52% of practices having ≤4 items. No practice had all eight basic items for circulation management, with 82% of practices having ≤4 of these items. Only two practices had all six basic drug items, with 85% of practices having ≤3 of these items. Only 26% of practices had algorithms for paediatric basic life support and common emergencies, and only 30% of practices kept their resuscitation equipment together. In the last 5 y, less than a fifth of general practitioners were trained in paediatric resuscitation.

Could lack of necessary equipment and training to manage common paediatric emergencies within primary healthcare centres impact on secondary healthcare services

Front line paramedics in the UK lack emergency paediatric equipment and skills.1 However, comparative assessments within primary healthcare centres have not been forthcoming, despite their potential propensity for paediatric emergencies and need for resuscitation drugs.2 Indeed, within our locality, East Midlands ambulances were summoned to 27 paediatric emergencies in the same centres surveyed in the preceding year. Moreover, in over …