bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of hyperthermia on uterine and umbilical blood flows in pregnant sheep
Authors: Andrianakis P , Walker D
Published: December 2014

Uterine and umbilical blood flows were measured in pregnant sheep (125‐142 days gestation) under normothermic and hyperthermic conditions using the Fick principle with [14C]antipyrine as the indicator. Exposure of the sheep to an ambient temperature of 43 +/− 1 degrees C (25‐30% relative humidity) for 8 h increased maternal and fetal core temperatures 1.19 +/− 0.15 and 1.39 +/− 0.12 degrees C respectively. Maternal hyperventilation caused a significant decrease of both maternal and fetal arterial partial pressure of CO2 (Pa,CO2) and increase of arterial pH. Uterine blood flow increased significantly during the hyperthermia (+54.2 +/− 14.1%), the increase being correlated with the magnitude of the decrease of maternal Pa,CO2 (r = ‐0.84, P < 0.05) but not with the increase of maternal core temperature. The increase of uterine blood flow was not associated with a concomitant increase in the placental clearance of [14C]antipyrine, a result which could arise if the increase of blood flow was non‐placental (i.e. did not occur within the cotyledons), or occurred through uterine arteriovenous shunts during the period of heat stress. Hyperthermia was not associated with a significant change of umbilical blood flow, placental transfer of glucose, or fetal glucose uptake. Since the loss of heat from the fetus occurs mainly across the placenta, we speculate that the apparent increase of uterine blood flow during maternal hyperthermia has an adaptive significance by maintaining conductive heat flux in a fetomaternal direction, even though cotyledonary (placental) blood flows did not increase.
High affinity of blood for oxygen reduces oxygen uptake in contracting canine gracilis muscle
Authors: Kohzuki H , Enoki Y , Sakata S , Shimizu S , Ohga Y
Published: December 2014

To clarify the influence of blood flow with high‐oxygen (O2)‐affinity blood on oxygen consumption (VO2) in submaximally exercising skeletal muscle, we perfused the isolated dog gracilis (n = 8) contracting under 1 Hz stimulation alternatively with normal and high‐O2‐affinity blood, with a constant arterial O2 content (Ca,O2) and varying perfusion rates. The average P50 (oxygen partial pressure (PO2) for half‐saturation at pH 7.40, PCO2 of 40 mmHg at 37 degrees C) of the high‐O2‐affinity blood prepared by carbamylation was 15.5 mmHg, and that of the normal blood 33.7 mmHg. With normal blood perfusion, the average VO2 above 6 ml min‐1 (100 g)‐1 of O2 delivery (Ca,O2 x flow) was 4.38 ml min‐1 (100 g)‐1 (range 4.17–4.68 ml min‐1 (100 g)‐1, and VO2 at the O2 delivery range of 6–5 and 4‐2.5 ml min‐1 (100 g)‐1 decreased to 3.96 and 2.43 ml min‐1 (100 g)‐1, respectively. The PO2 of venous effluent (Pv,O2) at the O2 delivery of 6 ml min‐1 (100 g)‐1 was 33 mmHg. With low‐P50 blood perfusion, VO2 was significantly less than with normal blood, both below the O2 delivery level of 6 ml min‐1 (100 g)‐1 and above it, even in the fairly high O2 delivery range of 8.5–12 ml min‐1 (100 g)‐1 (P < 0.05). Thus, high blood flow did not compensate for the reduced VO2 caused by high‐O2‐affinity blood. At values of Pv,O2 less than 33 mmHg, VO2 with low‐P50 blood was not significantly different from that with normal blood (P > 0.05). The reduced VO2 in submaximally exercising skeletal muscle might be due to a slower O2 dissociation from the high‐O2‐affinity red cells and to a limited O2 diffusion resulting from the lower Pv,O2 value (which reflects mean end‐capillary PO2).
Effects of low intensity infrared laser irradiation upon conduction in the human median nerve in vivo
Authors: Baxter GD , Walsh DM , Allen JM , Lowe AS , Bell AJ
Published: December 2014

The current investigation, for which ethical permission was obtained, was designed to assess the putative neurophysiological effects of low intensity (9.6 J/cm2) laser (830 nm) irradiation upon conduction latencies in the human median nerve in vivo. Antidromic nerve conduction studies were performed on the non‐dominant arms of healthy human volunteers (n = 51), who were each assigned to one of a variety of laser, placebo or control groups under randomized, blinded conditions. Analysis of negative peak latency differences using analysis of variance showed small (approximately 0.4 ms) but significant increases in latencies as a result of direct laser irradiation, and, where two‐site recording was used, distal to the site of irradiation. No such differences were seen in the other experimental groups. These results show that laser irradiation applied to intact skin at the parameters used here may produce a direct, localized effect upon conduction in underlying nerves.
Expression of c‐fos in the ovine brain following different types of stress, or central administration of corticotrophin‐releasing hormone
Authors: Vellucci SV , Parrott RF
Published: December 2014

Expression of c‐fos protein was examined in the brains of sheep (n = 2 per treatment) subjected to physical stress in a transport simulator, the psychological stress of isolation, insulin‐induced hypoglycaemia or intracerebroventricular (I.C.V.) injection of ovine corticotrophin‐releasing hormone (CRH). As control procedures, two sheep were given I.C.V. injections of saline and one animal received no treatment. Fos expression was induced in the hypothalamic paraventricular nucleus by transport simulation, isolation and hypoglycaemia, and also in the hypothalamic supraoptic nucleus by hypoglycaemia. Labelled nuclei were also seen in the brainstem in the region of the area postrema following transport simulation, isolation and insulin treatments. These results indicate that c‐fos expression in the ovine CNS is a useful marker for the identification of brain regions activated by stressors.
Catecholamine overflow within rat striatum: the influence of microstimulation and electroconvulsive stimulation as observed with voltammetry
Authors: Pavlasek J , Masanova C , Haburcak M , Murgas K
Published: December 2014

Differential pulse voltammetry with a carbon fibre microelectrode was used in chloral hydrate‐anaesthetized rats for testing the influence of microstimulation and of electroconvulsive stimulation on the changes in concentration of electro‐oxidizable materials (catechol derivates) in the extracellular space of the corpus striatum. Microstimulation applied in the striatum (8 V anodal pulses, 0.1 ms, 100 Hz for 40 s) caused a significant increase of the catechol‐oxidative current (Ico); 5 s after microstimulation was stopped Ico ranged from 117 to 141% of the control (all values means +/‐ S.D. unless otherwise stated; 124 +/‐ 11%, n = 4, P < or = 0.01, Student's t test). This effect ceased in the third minute after microstimulation. A comparable result was observed when microstimulation was repeated at intervals of 10 min. Electroconvulsive stimulation with a sinusoidal current (50 Hz, approximately 150 mA, 0.2 s) caused a large increase in Ico; 20 s after stimulation ceased, Ico was 987 +/‐ 90% (n = 3) of the control and it returned to the baseline 2 min later. The mechanisms inducing transmitter overflow are considered and the influence of electroconvulsive stimulation on the striatum is discussed in the context of its beneficial effects in psychopathic patients.
Excitation of soleus/gastrocnemius gamma‐motoneurones by group II knee joint afferents is suppressed by group IV joint afferents in the decerebrate, spinalized cat
Authors: Scott DT , Ferrell WR , Baxendale RH
Published: December 2014

Electrical stimulation sufficient to excite group II/III afferent fibres in the posterior articular nerve (PAN) of the cat knee joint facilitated gamma‐motoneurone firing in filaments of the lateral gastrocnemius/soleus (LGS) nerve. Repetitive (0.5‐2.0 Hz) electrical stimulation of the PAN, produced a short latency increase of gamma‐motoneurone firing with a latency ranging from 8 to 35 ms. The shortest of these delays suggests a segmental link between group II knee joint afferents and lateral gastrocnemius/soleus gamma‐motoneurones. This facilitation was diminished or abolished if the first stimulus was preceded by a conditioning stimulus which excited the group IV afferents in the PAN. This depression of facilitation was dependent on the interval between the test and conditioning stimuli and the interval which produced the greatest depression was consistent with the effect being due to group IV afferents. Inhibition of the facilitation did not significantly alter the on‐going discharge rate of the gamma‐motoneurones. This suggests that it was not due to direct inhibition of the motoneurones.
A faster twitch contraction of soleus in the spontaneously hypertensive rat is partly due to changed fibre type composition
Authors: Lewis DM , Levi AJ , Brooksby P , Jones JV
Published: December 2014

Contractile properties and fibre type composition of slow‐twitch soleus muscles from spontaneously hypertensive rats (SHR) were compared with those from a control normotensive strain (Wistar‐Kyoto, WKY). Male rats aged around 100 days were used, and muscle tension was recorded isometrically in vitro. Tetanic tension was reduced by about 15% in SHR; this decrease was highly significant when tension was expressed relative to muscle cross‐sectional area. Twitch contraction and relaxation were 12‐15% faster in SHR. There were no differences in the rate of rise of tension of either tetani or twitches, but the relaxation of tetanic tension was 17% faster in SHR. Twitch:tetanus ratios were 20% smaller in SHR. Histochemistry showed that SHR muscles had a threefold higher proportion of fast type II fibres compared to WKY. There were no significant changes in the contractile properties of the fast‐twitch extensor digitorum longus (EDL) muscles of SHR compared with WKY. Whilst the higher proportion of type II fibres could account for some of the contractile changes in SHR soleus muscles, the lack of any difference in the rate of rise of twitch and tetanic tension is not consistent. The faster rate of relaxation of both twitch and tetanus in SHR suggests that a higher rate of removal of calcium, either from the myofilaments or from the cytoplasm, may be an important factor in causing the changes in SHR soleus. The faster relaxation may be compared with a similar change reported in SHR cardiac myocytes.
Effects of parathyroid hormone and parathyroid hormone‐related protein on the rates of absorption of magnesium, calcium, sodium, potassium and phosphate ions from the reticulo‐rumen of sheep
Authors: Dua K , Leonhard S , Martens H , Abbas SK , Care AD
Published: December 2014

Not only parathyroid hormone (PTH) but also parathyroid hormone‐related protein (PTHrP) may play a role in calcium and phosphate homeostasis in ruminants. In five trained sheep, each with a large rumen cannula, the isolated rumen wash technique was used to measure electrolyte absorption rates from the rumen. After two control periods of measurement, 20 micrograms PTH(1‐34) (n = 4), or PTHrP(1‐34) (n = 5), was injected intravenously as a loading dose, followed by an infusion of 0.67 micrograms min‐1 over 2 h. Both PTH(1‐34) and PTHrP(1‐34) significantly increased the absorption rates of calcium and phosphate from the reticulo‐rumen. The increases in the absorption rates of magnesium, sodium and potassium observed were not significant. The same technique was also used to demonstrate that increasing the intraruminal calcium concentration from 1 to 4 mmol l(‐1) caused corresponding increases in the net rate of absorption of both calcium and inorganic phosphate from the reticulo‐rumen. Rumen epithelium was taken from four sheep and mounted in Ussing chambers so that fluxes of calcium could be measured in both directions using 45Ca. It was found that the addition of 100 ng ml‐1 PTH(1‐34) or PTHrP(1‐34) to the serosal side increased the net calcium flux rates across the ruminal epithelium. It is concluded that both PTH and PTHrP can influence calcium and phosphate homeostasis in sheep not only by their recognized actions on bone and kidney but also on the absorption of these ions from the forestomachs.
Blood amino acids in the pregnant mare and fetus: the effects of maternal fasting and intrafetal insulin
Authors: Silver M , Fowden AL , Taylor PM , Knox J , Hill CM
Published: December 2014

Blood amino acids were measured in twelve chronically catheterized mares and fetuses between 250 and 310 days gestation. The concentrations of the majority of individual amino acids were similar in maternal and fetal arterial blood and no gestational changes were detected. Only methionine, phosphoserine, 3‐methyl‐histidine and glutamine were consistently higher in the fetus than the mare, whilst certain other amino acids were higher in the maternal blood. Fasting the mares for 36 h led to significant falls in plasma glucose and rises in urea and maternal free fatty acids (FFA). Small but significant decreases in a few amino acids were seen in both fetus and mother, with an overall amino acid fall of 15% in the fetus and 13% in the mare. Virtually all amino acids had risen to basal values by 6 h after feeding. Intrafetal insulin (1 i.u./kg I.V.) as a bolus caused a more dramatic fall in fetal glucose than fasting, with no change in the mare. There were also rapid decreases in many amino acids by 30 min post‐insulin and by 2 h all but five amino acids had fallen significantly. There was a drop in total fetal blood amino acids of 29%. These findings show that, in contrast to most other species studied, there is no overall feto‐maternal gradient in blood amino acids in the mare, and that fasting leads to small falls in amino acid concentration, whereas intrafetal insulin induces a severe hypoglycaemia with dramatic decreases in almost all amino acids and no change in urea, suggesting a direct anabolic effect of insulin on fetal tissues.
Primary and secondary afferent discharges from the same spindle during chain fibre contraction in cat tenuissimus muscle
Authors: Celichowski J , Emonet‐Denand F , Gladden M , Laporte Y , Petit J
Published: December 2014

Pairs of Ia and II afferent fibres supplying primary and secondary endings lying in the same tenuissimus spindles were prepared in barbiturate anaesthetized cats in order to compare the variability in the rhythm of discharge of the two endings during responses elicited by the contraction of different intrafusal muscle fibres, especially by chain fibres. In these spindles, the intrafusal muscle fibres supplied by single static gamma‐axons were identified with a recently developed technique based on the types of primary ending activation observed during gamma stimulation at 30 and 100 stimuli/s. The responses of the secondary endings to contraction of chain fibres either alone or with bag2 fibres were smaller and much more regular than the responses of the primary endings lying in the same spindles. This difference is probably related to the position of secondary endings along the intrafusal muscle fibres and to the mechanical properties of the muscle fibre regions on which the terminals lie. The dynamic properties of the encoding site of primary afferent impulses probably contribute to the difference. The different degrees of variability observed among secondary ending responses elicited either by chain fibres alone or by chain and bag2 fibres are not related to the type of activated intrafusal muscle fibres.
Modulation of K(+)‐Cl‐ cotransport in equine red blood cells
Authors: Gibson JS , Godart H , Ellory JC , Staines H , Honess NA , Cossins AR
Published: December 2014

Potassium transport was measured in equine red blood cells, using 86Rb+ influx as a convenient assay. A significant component of volume‐ and pH‐sensitive K(+)‐Cl‐ cotransport to the overall K+ flux was observed in all blood samples studied, although fluxes were variable between animals, and within individuals when measured at intervals over a period of weeks. The aryloxyacetic acid [(dihydroindenyl)oxy]alkanoic acid (DIOA), at a final concentration of 100 microM, inhibited most (> 95%) of the Cl(‐)‐dependent K+ flux, and DIOA sensitivity was therefore used to define the activity of the K(+)‐Cl‐ cotransport. K(+)‐Cl‐ cotransport was also sensitive to protein phosphatase inhibition with calyculin A or okadaic acid, with inhibition constants of 9 +/− 1 nM for calyculin and about 100 nM for okadaic acid. Peak fluxes were observed at an external pH of 6.7–7.0, with inhibition at higher and lower values. Volume‐sensitive K+ fluxes assayed in autologous plasma, controlled for osmolaity, pH and potassium concentration, were significantly lower (28 +/− 8% of control values, n = 6) than those measured in saline. This inhibition was mimicked by the culture medium RPMI, but disappeared following dialysis of the plasma. Phosphate (5.6 mM) inhibited volume‐sensitive K+ fluxes by 48 +/− 2%, n = 3; no significant effect was observed by increasing external magnesium concentrations to 0.5 or 2 mM. Thus, inhibition by RPMI, but not that by plasma, may be due to phosphate. Finally, volume‐ and pH‐sensitive K+ fluxes were sensitive to oxygen tension and were abolished reversibly by equilibrating solutions with nitrogen, as opposed to air. Use of solutions equilibrated with different values of Po2 may account for some of the variability in equine red blood cell KCl fluxes. The importance of these observations to equine red blood cell homeostasis and haemodynamics is discussed.
Reflex respiratory responses to continuous and intermittent stimulation of afferent fibres from muscles in cats
Authors: Decandia M , Orani GP
Published: December 2014

In anaesthetized cats, reflex respiratory responses were evoked by electrically stimulating proximal ends of cut nerves to gastrocnemius‐soleus muscles of the left hindlimb. The direction of these responses, in the excitatory or inhibitory sense, depended on the types of afferent fibres stimulated and on the mode of stimulation. Continuous stimulation, delivered with stimuli of 0.1 ms at 200 or 300 Hz, in all cases induced excitatory responses, consisting of increases in pulmonary ventilation, mainly caused by increases in tidal volume. Intermittent stimulation, which consisted of brief trains of stimuli repeated at 2‐3 Hz, induced excitatory responses when afferent fibres with conduction velocities higher than 20 m/s were stimulated, while it induced inhibitory responses, consisting of decreases in pulmonary ventilation, tidal volume and respiratory frequency, when fibres with conduction velocities below 20 m/s were simultaneously stimulated with the high‐conduction velocity fibres.
Effects of ductus arteriosus occlusion on pulmonary artery pressure during in utero ventilation in fetal sheep
Authors: Giraud GD , Morton MJ , Reid DL , Reller MD , Thornburg KL
Published: December 2014

Seven fetal sheep were prepared to study the short‐term effects of in utero ventilation and ductus arteriosus occlusion on pulmonary artery pressure and on fetal right ventricular function assessed using the right atrial pressure‐right ventricular stroke volume relationship. Nine days post‐surgery (140 days gestation), blood gas and haemodynamic values were obtained before and during in utero ventilation with 100% O2, and during ventilation with the ductus arteriosus occluded. Oxygen content increased significantly from 7.2 to 14.5 ml dl‐1 with ventilation and remained elevated at 14.4 ml dl‐1 with ventilation with the ductus arteriosus occluded. In utero ventilation produced a left to right atrial pressure gradient and depression of the right atrial pressure‐right ventricular stroke volume relationship. Ductus arteriosus occlusion during in utero ventilation reduced the left to right atrial pressure gradient, and along with a decrease in pulmonary artery pressure, resulted in an upward shift of the right atrial pressure‐right ventricular stroke volume relationship, but only to the preventilation level. This study indicates that the fetal right atrial pressure‐right ventricular stroke volume relationship is significantly altered, both by changes in the left to right atrial pressure gradient and by changes in pulmonary artery pressure seen with in utero ventilation and subsequent ductus arteriosus occlusion.
Vaginal birth versus elective caesarean section: effects on gastric function in the neonate
Authors: Sangild PT , Hilsted L , Nexo E , Fowden AL , Silver M
Published: December 2014

Plasma gastrin concentration increases in late gestation and reaches a peak at birth or shortly after birth in many species (‘neonatal hypergastrinaemia’). We investigated the hypothesis that gastrin and gastric acid secretion in the neonate is influenced by the final rise in plasma cortisol associated with spontaneous (vaginal) birth. Caesarean‐delivered (CD, n = 28) or vaginally delivered (VD, n = 24) premature or full‐term piglets (97–115 days gestation) were killed immediately after birth (using pentobarbitone). Compared with newborn CD pigs, the newborn VD pigs had significantly higher (P < 0.05) concentrations of cortisol (669 +/− 60 versus 223 +/− 2 nM) and gastrin (57 +/− 4 versus 33 +/− 1 pM) in plasma, and significantly lower gastric fluid pH (3.3 +/− 0.2 versus 4.7 +/− 0.3), amidated (bioactive) gastrin in the antrum (550 +/− 77 versus 1220 +/− 29 pmol g‐1) and glycine‐extended (precursor) gastrin in the antrum (81 +/− 10 versus 143 +/− 5 pmol g‐1). There were significant linear correlations between log plasma cortisol values and plasma gastrin (r = 0.40, P < 0.05) or gastric fluid pH (r = ‐0.51, P < 0.05) in newborn pigs. The effects of cortisol in the immediate postnatal period were investigated in forty‐one CD pigs born at 111‐112 days gestation and treated with saline, metyrapone (an inhibitor of cortisol synthesis) or adrenocorticotrophic hormone (ACTH) from 0 to 7 days after birth. At 7 days, plasma gastrin in ACTH‐treated pigs (elevated plasma cortisol) was significantly lower than in saline‐treated pigs, but not different from that in metyrapone‐treated pigs (low plasma cortisol). No treatment effects were observed postnatally for antral gastrin and fundic cobalamin‐binding protein concentrations. These results suggest that in the intrapartum period the high circulating cortisol levels stimulate the normal rise in gastrin and acid secretion associated with spontaneous vaginal delivery in the piglet, whereas postnatally, cortisol is unlikely to play an important role in the subsequent development of gastrin and acid secretion.
Contribution of extracellular calcium to intracellular pH‐induced changes in spontaneous force of rat portal vein
Authors: Taggart MJ , Austin C , Wray S
Published: December 2014

Normal spontaneous mechanical activity of isolated rat portal vein is critically dependent on external calcium as a source of contractile activation and this force is modified by alteration of intracellular pH. We have studied the involvement of the extracellular calcium pool in intracellular pH‐induced changes in force. Intracellular pH was changed, at constant external pH, by NH4Cl application and withdrawal in bathing [CaCl2] varying between 3 and 0 mM, and manoeuvres were performed in the presence and absence of either the intracellular calcium mobilizer caffeine or the calcium channel blocker nifedipine. The results indicate that alteration of spontaneous force with intracellular pH has an absolute requirement for calcium entry from outside and calcium release from caffeine‐sensitive intracellular stores.
Neuropeptidergic and autonomic control of the vasculature of the rat knee joint revealed by laser Doppler perfusion imaging
Authors: Karimian SM , McDougall JJ , Ferrell WR
Published: December 2014

An imaging technique (laser Doppler perfusion imaging, LDI), based on measurement of backscattered Doppler‐broadened laser radiation, was used to provide two‐dimensional images of perfusion in the exposed rat knee joint capsule. In control animals, frequency‐dependent constriction of knee joint blood vessels occurred during electrical stimulation of sympathetic nerve fibres whilst dose‐dependent vasodilatation of these vessels was elicited by direct application of the sensory neuropeptide substance P (SP) to the capsule. Intra‐articular injection of the neurotoxic agent capsaicin did not affect vasoconstrictor responses when tested 5–7 days later, but substantially reduced dilator responses to SP. These findings indicate that capsaicin is selectively neurotoxic for sensory unmyelinated fibres but not sympathetic postganglionic fibres and is also capable of modifying receptor‐mediated effects of SP. LDI is a useful method for mapping tissue perfusion, particularly in structures such as joints where the spatial distribution of blood flow is heterogeneous.
EB 1089, a calcitriol analogue, decreases fetal calcium content when injected into pregnant rats
Authors: Davicco MJ , Coxam V , Gaumet N , Lebecque P , Barlet JP
Published: December 2014

EB 1089 is a calcitriol analogue with low calcaemic activity, which inhibits parathyroid hormone‐related peptide (PTHrP) secretion in rats implanted with the Leydig cell tumour H‐500. We have studied its effect on maternal and fetal plasma PTHrP concentrations and on fetal calcium and phosphorus contents in rats. Three groups of six pregnant rats were injected I.P. daily with EB 1089 (0.10, 0.25 and 0.50 microgram kg‐1 in groups 1, 2 and 3, respectively, from day 12 to day 20 of gestation). The control group received an equal volume of solvent alone. On day 21 of gestation the animals were anaesthetized with chloral hydrate and blood samples were taken. Fetuses were collected, weighed and ashed for Ca and P measurements. PTHrP concentrations were measured by radioimmunoassay (RIA) in maternal and fetal plasma. Calcium content (mg (g fetal wt)‐1; mean +/− S.E.M.) in control fetuses was not different from that measured in fetuses from dams given the lowest dose of EB 1089, but was higher than that in fetuses from rats injected with EB 1089 at 0.25 microgram kg‐1 (1.18 +/− 0.20; P < 0.05) or 0.50 microgram kg‐1 (1.08 +/− 0.29; P < 0.05). There was no difference in fetal P content between any of the groups of rats. The PTHrP concentration (pg equivalents human PTHrP(1‐34) fragment ml‐1) in maternal plasma from control rats (1.70 +/− 0.50) was not different from that in maternal plasma of rats given the lowest dose of EB 1089 (1.44 +/− 0.63).(ABSTRACT TRUNCATED AT 250 WORDS)
The glucogenic capacity of the fetal pig: developmental regulation by cortisol
Authors: Fowden AL , Apatu RS , Silver M
Published: December 2014

In the present study, the ontogenic changes in gluconeogenic enzyme activities and in hepatic glycogen and beta‐adrenergic receptor levels were investigated in fetal pigs from 70 days of gestation until delivery at term (114 +/− 2 days). The values were compared with those observed in fetuses infused subcutaneously with cortisol for 6 days beginning at 82‐84 or 92‐94 days of gestation. Tissue glucose‐6‐phosphatase (G6Pase) activity increased with increasing gestational age in the liver, kidney and duodenum of control fetal pigs. At birth, there was a further increase in G6Pase activity in the liver but not in the kidney or duodenum. In the kidney, there was a similar gestational increase in phosphoenolpyruvate carboxykinase (PEPCK) activity. These changes in enzyme activities closely paralleled the prepartum increase in fetal plasma cortisol and were accompanied by increases in hepatic glycogen content and beta‐adrenergic receptor density. At 98–100 days, there were significant increases in G6Pase activity in the liver, kidney and duodenum of the cortisol‐infused fetuses, whereas at 88‐90 days only renal G6Pase was significantly elevated by cortisol infusion. Cortisol infusion also increased hepatic beta‐receptor density at 88‐90 days and hepatic glycogen content at both gestational ages. There were no changes in hepatic PEPCK, hepatic or renal fructose diphosphatase and aspartate amino transferase activities during cortisol infusion or with increasing gestational age. When the data from all the piglets were combined, irrespective of age or treatment, there were significant positive correlations between log plasma cortisol and G6Pase activity in the liver, kidney and duodenum. Similar positive correlations were observed between hepatic beta‐adrenoceptor density and log plasma cortisol and between the latter values and the hepatic glycogen content. These findings show that cortisol induces tissue G6Pase activity in the fetal pig and suggest that the prepartum rise in endogenous cortisol may be responsible for the increase in fetal glucogenic capacity observed towards term in this as in other species.
Effect of oral corticosterone administration on locomotor development of neonatal and juvenile rats
Authors: Pavlovska‐Teglia G , Stodulski G , Svendsen L , Dalton K , Hau J
Published: December 2014

In order to simulate the elevated corticosteroid levels to which offspring of stressed women may be subjected, rat pups were treated daily with two levels of oral corticosterone from the 2nd to the 15th postnatal day. The rat pups were subjected to swimming tests from their 8th postnatal day to examine their neuromuscular development and learning abilities. The locomotor performance of corticosterone‐treated groups was similar to that of controls but its development was delayed, which demonstrates that even relatively low levels of corticosterone have a significant negative influence on the maturation and learning ability of neonatal rat pups. This indicates that the glucocorticoid levels to which suckling neonates (for example, children of women suffering from stress) might be exposed could modify the complex integrated neuromuscular adaptive mechanisms involved in normal locomotor development.
The effects of glibenclamide on tetanic force and intracellular calcium in normal and fatigued mouse skeletal muscle
Authors: Duty S , Allen DG
Published: December 2014

In this study the effects of ATP‐sensitive K+ channel modulators were studied in intact single fibres dissected from mouse skeletal muscle. Indo‐1 was used to measure [Ca2+]i simultaneously with force during normal and fatiguing stimulation. In control fibres, opening of ATP‐sensitive K+ channels with BRL 38227 produced a small reduction in tetanic force and [Ca2+]i. In contrast, glibenclamide, a selective blocker of the ATP‐sensitive K+ channel, slightly increased tetanic force and [Ca2+]i in these fibres and also increased Ca2+ sensitivity. Glibenclamide produced a more marked increase in tetanic force and [Ca2+]i during the later stages of fatiguing stimulation, although this effect was observed in only 50% of fibres examined. We conclude from this study that glibenclamide produces a partial reversal of the later stages of fatigue in a subpopulation of muscle fibres. Opening of ATP‐sensitive K+ channels may therefore contribute to the decline in tetanic force and [Ca2+]i characteristic of skeletal muscle fatigue.
Ca2+ release channels in rat denervated skeletal muscles
Authors: Delbono O , Chu A
Published: December 2014

Sarcoplasmic reticulum (SR) Ca2+ release channel‐ryanodine receptors (RYR1) from rat fast‐twitch skeletal muscle were studied by incorporating heavy sarcoplasmic reticulum membranes into a lipid bilayer. Channels from normal and denervated muscles had the same conductance as that reported for rabbits (about 500 pS) in 250:250 mM cis:trans caesium methanesulphonate. Caffeine (0.1 mM) induced a larger increase in the open probability (Po) in denervated than in normal channels. The caffeine effect was caused by changes in mean open and burst time distributions. Longer opening and burst events were detected in the presence of caffeine. High caffeine concentrations (4 mM) gave similar results in channels from normal and denervated muscles. In denervated muscle, unlike intact muscle, the Ca2+ release channel was not activated at millimolar Ca2+ concentrations; this is similar to the cardiac isoform of the channel. Maximal channel activation was shifted to higher Ca2+ concentrations (pCa 4) and the channel remained activated at millimolar Ca2+ concentrations. The main effect of millimolar Ca2+ concentrations upon Ca2+ release channels from denervated muscles was an increase in the mean open time, with a concomitant increment of the mean burst duration. Alterations in channel gating properties in calcium and caffeine account for changes in the mechanical response after skeletal muscle denervation.
Penetration of small molecular weight substances through cultured bovine brain capillary endothelial cell monolayers: the early effects of cyclic adenosine 3',5'‐monophosphate
Authors: Deli MA , Dehouck MP , Abraham CS , Cecchelli R , Joo F
Published: December 2014

Second messengers, such as cyclic adenosine 3',5'‐monophosphate (cAMP), have been shown to take part in the regulation of blood‐brain barrier permeability. In the present study, elevation of cAMP levels decreased sucrose (mol. wt, 342) and inulin (mol. wt, 5000) permeability across monolayers of bovine brain capillary endothelial cells as early as 1 h after exposure. Since both tracers use predominantly a paracellular pathway, we assume that cAMP may increase the tightness of the tight junctions through protein phosphorylation.
Environmental effects on thermoregulation and breathing patterns during early postnatal development in hand‐reared lambs
Authors: Symonds ME , Andrews DC , Buss DS , Clarke L , Darby CJ , Johnson P , Lomax MA
Published: December 2014

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.
Clinical aspects of hypoxic pulmonary vasoconstriction
Authors: Leach RM , Treacher DF
Published: December 2014

Although frequently unrecognized, hypoxic pulmonary vascular disease is an important cofactor in the morbidity and mortality of a wide spectrum of disease processes. The hypoxic response incorporates two distinct phases, the acute hypoxic vasoconstrictor response and vascular remodelling associated with prolonged alveolar hypoxia. Understanding of the mechanisms causing both processes has increased rapidly and may result in the near future in specific treatment aimed at correcting underlying physiological abnormalities. However, currently available therapies remain limited to correction of the hypoxaemia and generalized non‐specific pulmonary vasodilatation. The recent development of inhaled NO therapy represents a significant advance in the management of the acute hypoxic pulmonary vasoconstriction occurring during critical illness.
The voltage dependence of contraction at different stimulation rates in guinea‐pig ventricular myocytes
Authors: Harrison SM
Published: December 2014

Ventricular myocytes, isolated from the guinea‐pig, were stimulated to contract by 100 ms long voltage clamp pulses from ‐80 to 0 mV at 0.5 and 3 Hz. An increase in frequency from 0.5 to 3 Hz led to a positive inotropic effect. Contraction‐voltage relationships (CVR) were determined at each frequency. The CVR at 0.5 Hz was bell shaped and peaked between 0 and +20 mV, displaying a voltage dependence similar to the L‐type Ca2+ current (ICa). At 3 Hz, contractions continued to increase at positive voltages, giving a more sigmoidal CVR. At 0.5 Hz, TTX reduced the size of steady‐state contractions to 91 +/− 2% of control values, but had no effect on the shape of the CVR. At 3 Hz, TTX significantly reduced (P < 0.05) the magnitude of contractions at positive voltages (> or = +20 mV) but had no significant effect on contractions at voltages negative to 0 mV. These data illustrate that intracellular sodium activity (aNa(i)) and, in particular, Na+ entry due to the sodium current (INa) are important in determining the voltage dependence of contraction at positive voltages. Thapsigargin (2.5 microM), a blocker of the sarcoplasmic reticulum (SR) Ca(2+)−ATPase, reduced the size of steady‐state contractions at 0 mV to 65 +/− 7% at 0.5 Hz. Increasing frequency to 3 Hz abolished the positive inotropy seen under control conditions. With thapsigargin present, contractions at 0.5 Hz were reduced at all potentials and the CVR was bell shaped. At 3 Hz the CVR was sigmoidal in shape. Contractions were significantly inhibited by thapsigargin at all potentials, but most significantly at more positive potentials (> or = +20 mV). These data show that, at normal body temperature, the shape of the CVR of guinea‐pig ventricular myocytes changes with stimulation rate. Due to the voltage dependence of ICa, contractions evoked at positive voltages at 3 Hz must be supported by other mechanisms. The sensitivity of such contractions to TTX and thapsigargin suggests the involvement of both a Na(+)−dependent process and the SR. One possibility is that when aiNa and the Ca2+ content of the SR are raised at higher stimulation rates, enhanced Ca2+ entry via reverse Na(+)−Ca2+ exchange leads to a direct activation of the myofilaments and, to a lesser extent, the release of Ca2+ from the SR.
Resistance to glomerular injury in the diabetic biobreeding rat
Authors: Feld LG , Cachero S , Ellis EN , Dedeoglu O , Ueda Y , Leonard C , Letizia R , Mallon V , Van Liew JB
Published: December 2014

This study was designed to determine whether the diabetic BioBreeding rat develops significant renal injury following long‐term moderate to severe hyperglycaemia. Diabetic and control rats were followed from the onset of diabetes (2‐4 months) to 18 months of age. Frank proteinuria and/or albuminuria were always absent. Glomerular filtration rate, measured by inulin clearance (ml min‐1 (100 g body weight)‐1), was significantly higher in diabetic rats than in controls at 10, 12 and 18 months of age. Advanced glycosylation end‐product cross‐links assessed by percentage solubility of tail tendon collagen were moderately increased in diabetic compared with control animals. Urinary excretion of advanced glycosylation end‐products in unfractionated urine and in urine fractionated for low molecular mass peptides (< 10 kDa) was 11‐fold greater in the diabetic rats than in the control group. Urinary excretion of nitric oxide metabolites (nmol NO2‐ and NO3‐ (24 h)‐1) were significantly (P < 0.05) greater in diabetic rats than in controls after 8 months of age. Mild histopathology resembling human diabetic nephropathy, including increased mesangial volume and glomerular basement membrane thickness, was detected at 18 months of age. The findings of hyperfiltration and mild glomerular morphological changes in diabetic BioBreeding rats are similar to the abnormalities seen in stage 2 human diabetic nephropathy. We hypothesize that two factors which may contribute to the resistance or tolerance to renal injury in the BioBreeding diabetic rat are increased nitric oxide production and the decreased accumulation of advanced glycosylation end‐products.
Responses of glucose metabolism to insulin in perfused mammary tissue of lactating rats: influence of dietary history and recent insulin experience
Authors: Calvert DT , Clegg RA
Published: December 2014

Mammary tissue of lactating rats has been perfused in situ to measure the effects of insulin and of previous dietary history on utilization of glucose and its incorporation into lipid. This experimental model allows the direct effects of insulin on mammary tissue to be characterized without influence from the secondary consequences of insulin administration that may accompany treatment of the intact animal with this hormone. In mammary tissue from rats starved for 24 h, glucose utilization was stimulated by insulin treatment. The threshold for insulin response was between 0.01 and 0.02 mU ml‐1, and no further stimulation took place between 0.02 and 0.04 mU ml‐1 insulin. The maximum response was reached within 50 min of the onset of insulin challenge and remained at a plateau value regardless of whether insulin was continuously present or was withdrawn after 15 min. Incorporation of glucose into lipid contributed to this glucose uptake. When no insulin was present in the perfusate, the rate of this process was around 3‐fold greater in perfused mammary tissue from fed lactating rats than from those starved for 24 h. Insulin accelerated lipogenesis from glucose approximately 3‐ and 2‐fold, respectively, in these two experimental groups. As for glucose uptake, the role of insulin in the regulation of mammary lipogenesis appeared to be to ‘prime’ the tissue and commit it to a response that was subsequently insulin independent.
Physiological regulation of gaba uptake by rat pyloric antral mucosa
Authors: Varro A , Athanassopolous P , Dockray GJ
Published: December 2014

Endocrine cells of the pyloric antral mucosa are known to take up gamma‐amino‐n‐butyric acid (GABA), but the functional significance of this is uncertain. We now report that specific uptake of [3H]GABA by rat antral, but not corpus, mucosa is enhanced after fasting for 48 h. Decreased extracellular GABA in fasted rats could account for known changes in antral endocrine cell function.
The action of knee joint afferents and the concomitant influence of cutaneous (sural) afferents on the discharge of triceps surae gamma‐motoneurones in the cat
Authors: Ellaway PH , Davey NJ , Ferrell WR , Baxendale RH
Published: December 2014

Electrical stimulation of group II joint afferents of the posterior articular nerve (PAN) to the knee evoked short‐latency facilitation and/or inhibition of the background discharge of gastrocnemius‐soleus (GS) gamma‐motoneurones in decerebrated spinal cats. The latencies of these responses were consistent with mediation via segmental oligosynaptic spinal pathways. In addition, a longer‐latency facilitation was frequently observed. Mechanical non‐noxious stimulation of the skin within the field of innervation of the sural nerve, on the lateral aspect of the heel, suppressed the short‐latency facilitation, but not the inhibition or long‐latency facilitation. Brief mechanical indentation of the posterior aspect of the knee joint capsule could elicit facilitation or inhibition of gamma‐motoneurones. Facilitation, but not inhibition, was blocked by anaesthesia or section of the PAN. Both actions could be suppressed by mechanical stimulation of the heel. We conclude that GS gamma‐motoneurones receive both facilitatory and inhibitory segmental inputs from group II articular afferents arising in the knee joint. Cutaneous afferents from the sural field exert a selective inhibitory influence over the facilitation of fusimotor discharge by articular afferents.
Transport of sodium across the isolated bovine rumen epithelium: interaction with short‐chain fatty acids, chloride and bicarbonate
Authors: Sehested J , Diernaes L , Moller PD , Skadhauge E
Published: December 2014

Unidirectional transport rates of sodium (22Na+) and chloride (36Cl‐) across bovine rumen epithelium were measured in vitro by the Ussing chamber technique. The active and short‐chain fatty acid (SCFA)‐stimulated sodium transport was shown to fit Michaelis‐Menten kinetics, and was rate limited mainly by one transport system, characterized by a Km of 43 mmol l‐1 Na+ and a Jmax (maximal transport rate) of 6.2 mumol cm‐2 h‐1 Na+. It was confirmed that the basolateral Na+,K(+)‐ATPase was essential for active sodium transport, and that an apical amiloride‐sensitive sodium transport system (Na(+)‐H+ exchange) was involved in a minimum of 60‐70% of the active sodium transport in the presence of SCFAs (butyrate). The main part of both the mucosal‐serosal (MS) and serosal‐mucosal (SM) sodium flux was sensitive to an applied electrical potential difference (PD). It is noteworthy that an applied PD, equal to the in vivo PD (+30 mV, lumen as reference), abolished net transport of sodium. The stimulating effect of a mixture of acetate, propionate and butyrate on active sodium transport was confirmed, and it was further shown that the stimulating effect of each of the three SCFAs was nearly equal. Analogues of naturally occurring SCFAs (isobutyrate and 2‐ethyl‐butyrate) did not stimulate active sodium transport, but inhibited the stimulating effect of butyrate. The stimulating effect of butyrate was clearly concentration dependent and showed a maximum at approximately 20 mmol l–1 butyrate. Above this limit active sodium transport was decreased with increasing butyrate concentration. This suggests that there was a limit to the amount of butyrate that could be handled by the epithelium. The active sodium transport was clearly correlated with the chloride concentration, and was significantly reduced, but not abolished, by replacement of chloride with gluconate. Active transport of chloride was stimulated by butyrate and reduced by the Na(+)‐H+ exchange inhibitor amiloride (3 mmol l–1). There was no effect of the Cl(‐)‐HCO3‐ exchange inhibitor DIDS (4,4'‐diisothiocyanatostilbene‐2,2'‐disulphonic acid; 0.5 mmol l–1) on sodium transport. HCO3‐ (13 mmol l–1) and CO2 (5%) themselves had only a small and non‐significant stimulating effect on sodium fluxes, however, in the presence, but not the absence of HCO3‐ and CO2 in the experimental solutions acetazolamide (1 mmol l–1) significantly reduced active sodium transport. It is concluded that SCFAs could stimulate the active sodium and chloride transport as a result of their metabolism. The CO2 produced could stimulate apical Na(+)‐H+ and Cl(‐)‐HCO3‐ exchangers running in parallel via increased H+ and HCO3‐ gradients.