bluuebunny/crossref_metadata_2025 huggingface dataset:
PITUITARY‐ADRENOCORTICAL ACTIVITY IN THE FETAL PIG IN THE LAST THIRD OF GESTATION
Authors: Silver M. , Fowden A. L.
Published: December 2014

The responsiveness of the fetal adrenal to a rise in either endogenous or exogenous ACTH (adrenocorticotrophic hormone) was examined acutely in piglets between 70 and 105 days gestation (term, 115 days). In addition the pre‐partum changes in plasma ACTH and cortisol were followed in chronically catheterized fetuses and the effect of a continuous intrafetal ACTH infusion on the time of delivery was also investigated. The acute experiments on ten sows were carried out (under sodium pentobarbitone) on twenty‐five fetuses, sampled from a branch of the umbilical artery with minimal disturbance. A second sample was taken 10‐20 min later after exteriorization or surgery (catheterization). Such fetal manipulation resulted in significant increases in plasma ACTH and cortisol from 70 days gestation and the responses increased with fetal age. No corresponding changes were seen in the controls or in the sow over the same period. An exogenous bolus of ACTH (200 ng ml−1 I.V.) evoked rises in fetal plasma cortisol comparable with the endogenous changes (+11 ± 2 ng ml‐1, n = 4). Chronic experiments were carried out on fourteen sows catheterized under sodium pentobarbitone anaesthesia at 95‐100 days gestation; in fetuses sampled until delivery (at 111‐114 days) gradual rises in both fetal plasma cortisol and ACTH were observed. There was a highly significant positive correlation between plasma cortisol and log plasma ACTH (r = 0·81, n = 52, P 〈 0·001). Analysis of the basal values from the 70‐100 day fetuses also showed a positive correlation (r = 0·47, n = 23, P 〈 0·05) but the slope of the regression line was significantly less than that for the older fetuses indicating a greater adrenocortical response to a given level of ACTH nearer term. In five sows a continuous infusion of ACTH (0·125 mg day−1 for 4‐5 days from about 100 days) was given to one or two fetuses per litter (total size, 7‐12). This treatment resulted in a rise in fetal plasma cortisol to 85·4 ± 8·9 ng ml−1, which was equivalent to that found during labour, but did not induce premature parturition.
NEW EVIDENCE THAT L‐GLUTAMATE IS A TRANSMITTER AT THE SQUID GIANT SYNAPSE
Authors: De Santis A. , Messenger J. B.
Published: December 2014

Experiments are described showing unequivocally that transmission at the squid giant synapse can be reversibly blocked by L‐glutamate and its agonists kainate, quisqualate and AMPA, though not by NMDA. This effect is presumably brought about by desensitization. The glutamate antagonists cis‐2,3‐PDA, GAMS and the new quinoxalinediones CNQX and DNQX are also potent reversible blockers. These findings provide new evidence that L‐glutamate is a transmitter at the giant synapse and further suggest that the glutamate receptor may be of the non‐NMDA type.
ADAPTATION AND BURSTING IN NEOCORTICAL NEURONES MAY BE CONTROLLED BY A SINGLE FAST POTASSIUM CONDUCTANCE
Authors: Berman N. J. , Bush P. C. , Douglas R. J.
Published: December 2014

We have used computer simulation of a model neurone and in vitro intracellular recording to demonstrate that the adaptation of repetitive discharge in neocortical neurones can be explained by a fast potassium current whose inactivation is retarded by intracellular calcium. The maximum amplitude of this current determines whether the neurone will discharge in regular or burst mode.
MEASURING SHORT‐TERM RATES OF MILK SYNTHESIS IN BREAST‐FEEDING MOTHERS
Authors: Arthur Peter G. , Spruce Janice , Hartmann Peter E. , Jones Trevor J.
Published: December 2014

A Moire contouring method was used to measure changes in the volume of the breast between infant feeds. A tungsten‐halogen light source obliquely illuminated the breast through a moving Moire grid to produce contour shadows on the breast. Photographs of the Moire topographs were analysed to obtain three‐dimensional co‐ordinates of transverse sections through the breast. The cross‐sectional areas were calculated using the trapezoidal rule and volumes were calculated by multiplying these areas by their vertical separation. The precision of the method was found to be dependent on the subject repositioning accurately. With careful control over subject posture and position the relative standard deviation was 1·8%, but without careful repositioning the relative standard deviation was 10%. The Moire topography method was accurate; the mean difference between changes in the volume of the breast after breast feeding as measured by the Moire topography method and test weighing was 0·34 ± 7·26 ml (n = 21). For two women, the rate of increase in the volume of the right breast was found to range from 13 to 40 ml/h.
PLASMA ENTEROGLUCAGON, GASTRIN AND PEPTIDE YY IN CONVENTIONAL AND GERM‐FREE RATS REFED WITH A FIBRE‐FREE OR FIBRE‐SUPPLEMENTED DIET
Authors: Goodlad R. A. , Ghatei M. A. , Domin J. , Wright N. A. , Ratcliffe B. , Fordham J. P. , Bloom S. R.
Published: December 2014

Germ‐free rats and conventional rats were starved and then refed with either an elemental diet (Flexical), or Flexical plus 30% kaolin, or Flexical plus 30% of a fibre mixture. Plasma levels of enteroglucagon, gastrin and peptide YY (PYY) were all significantly affected by diet. Enteroglucagon and especially PYY were significantly increased by the addition of fermentable fibre to the diet, but only in the conventional, not in the germ‐free rats. Gastrin was not affected by the addition of fermentable fibre, but was increased by kaolin. Enteroglucagon and PYY were, however, both very much elevated in the germ‐free animals, in which there is no proliferative response to fibre. Enteroglucagon and PYY levels were similar to those usually associated with extreme hyperproliferative states, indicating that it is unlikely that these hormones are involved in the proliferative response of the gastrointestinal tract to dietary fibre, and casting doubt on their role in other responses.
EFFERENT LIMB OF THE ATRIAL RECEPTOR REFLEX DECREASE IN PLASMA RENIN ACTIVITY IN ANAESTHETIZED DOGS
Authors: Drinkhill M. J. , Vacca G. , Mary D. A. S. G.
Published: December 2014

The efferent limb of the reflex response of a decrease in plasma renin activity in response to stimulation of atrial receptors was examined in two groups of experiments in anaesthetized dogs. The atrial receptors were discretely stimulated by distension of small balloons in the left pulmonary vein‐atrial junction and in the atrial appendage. In the first group, in which the responses of tachycardia and natriuresis were blocked, the diuretic response was accompanied by decreases in plasma renin activity. This decrease was abolished in the second group by renal denervation. The results have shown that the efferent limb of the response of a decrease in plasma renin activity involved the renal nerves.
WATER ABSORPTION FROM THE PIG PROXIMAL COLON: RELATIONS WITH FEEDING AND FLOW OF DIGESTA
Authors: Theodorou V. , Fioramonti J. , Buéno L.
Published: December 2014

Net water absorption from the proximal colon was determined at 2 h intervals for 10 h after a meal in four pigs chronically fitted with two cannulas in the proximal colon (1st and 2nd coil) and a catheter in the ileum. Water flux was measured by infusing a marker (51Cr‐EDTA) at a constant rate into the ileum and by sampling colonic content through the cannulas. Two hours after the meal water was absorbed by the colonic segment situated between the two cannulas at a rate of 0·7 ± 0·1 ml/min. Then the net water absorption increased progressively and reached a maximum ( 1·7 ± 0·3 ml/min) 8 h after eating. These postprandial changes in water absorption were positively correlated (r = 0·63, n = 40) with changes in the flow of digesta at the level of the proximal cannula. The concentration of volatile fatty acids and the osmolality of the digesta, as well as the transit time of a marker (phenolsulphonphthalein) between the two cannulas, did not significantly fluctuate after the meal and were not correlated with water absorption. Antibiotic treatment for 3 days (neomycin, 15 g/day, continuously infused into the ileum) induced a 90% decrease in volatile fatty acid concentration but did not modify colonic water absorption nor its postprandial changes. These results show a postprandial pattern of colonic water absorption which is mainly controlled by the flow of digesta into the colon.
AMILORIDE REDUCES MATERNOFETAL CLEARANCE OF SODIUM ACROSS THE NEAR‐TERM RAT PLACENTA
Authors: Atkinson D. E. , Sibley C. P. , Robinson N. R.
Published: December 2014

The effect of amiloride on unidirectional maternofetal clearance across the perfused placenta has been studied in rats at 21 days gestation. A bolus dose of 1 mg kg−1 followed by an infusion of 0·6 mg h−1 into the maternal circulation caused a significant (P 〈 0·02) decrease in 22Na clearance by 8%, whilst having no effect on the clearance of 51Cr‐EDTA; a ten times higher dose of amiloride (10 mg kg∓1, 6 mg h−1) did not reduce 22Na clearance further. Similar administration of an equivalent volume of saline to control animals showed no effect on either Na+ or Cr‐EDTA clearances.
UPTAKE OF AMINO ACIDS AND AMMONIA AT MID‐GESTATION BY THE FETAL LAMB
Authors: Bell Alan W. , Kennaugh Jan M. , Battaglia Frederick C. , Meschia Giacomo
Published: December 2014

Fetal uptakes of amino acids and ammonia via the umbilical circulation were measured in single pregnant ewes at mid‐gestation (range 66‐81 days). There were significant net fluxes from placenta to fetus of ammonia and twelve amino acids (in decreasing order: glutamine, glycine, alanine, proline, lysine, arginine, threonine, valine, leucine, tyrosine, asparagine, isoleucine) and net fluxes from fetus to placenta of glutamate and serine. The estimated serine flux was 139 µmol day−1 (g fetal dry wt)−1. Comparison with late gestation data indicated a similar pattern of amino acid exchange. However, the relatively large placental uptake of fetal serine was a distinctive feature of mid‐gestation. The net fetal uptake of amino acid nitrogen was 2·83 ± 0·66 µg N (µmol O2 uptake)−1, or 18 mg N day−1 (g dry wt)−. This uptake was similar in magnitude to the combined fetal requirements for nitrogen accretion and urea synthesis and represented approximately 32 and 43% of fetal carbon and energy requirements, respectively.
STRUCTURE AND FUNCTION OF THE CAROTID BODY IN NEW ZEALAND GENETICALLY HYPERTENSIVE RATS
Authors: Bee Denise , Barer Gwenda , Wach Richard , Pallot David , Emery Celia , Jones Stephen
Published: December 2014

Morphology of the carotid body and the ventilatory response to hypoxia were compared in New Zealand genetically hypertensive rats and ‘normotensive’ control rats from the same genetic stock. Hypertensive rats grew more slowly, had higher blood pressure from 6 weeks of age and developed left ventricular hypertrophy. Carotid bodies of both groups were similar in size but larger than those of a common Wistar strain. Intimal damage and proliferation were seen in 1st‐ and 2nd‐order branches of the carotid body artery in hypertensive rats and point‐counting showed that the volume proportion of Type 1 cell nuclei and vascular lumen was reduced and vascular wall increased. In age‐matched anaesthetized rats, minute ventilation per 100 g was greater in hypertensives than ‘normotensives’ when inspiring O2 concentrations of 30, 21, 18, 15, 12, 10 and 8%. However, at each inspired O2 concentration, arterial Pa,O2 was higher and Pa,CO2 lower in hypertensive than in ‘normotensive’ rats. Hypertensive rats were hyperventilating. The shape of the ventilation/O2 tension curve was similar in hypertensive and ‘normotensive’ rats; thus carotid body sensitivity to hypoxia was probably unchanged. Possible causes of hyperventilation and the relation of carotid body morphology to hypertension are discussed.
PATCH CLAMP TECHNIQUES USED FOR STUDYING SYNAPTIC TRANSMISSION IN SLICES OF MAMMALIAN BRAIN
Authors: Sakmann B. , Edwards F. , Konnerth A. , Takahashi T.
Published: December 2014

Procedures are described for recording postsynaptic currents from neurones in slices of rat brain using patch clamp techniques. The method involves cutting brain slices (120‐300, µm thick) with a vibrating microtome followed by localization of cell somata, which can be clearly seen with Nomarski differential interference contrast optics in the light microscope. Tissue covering the identified cell is then removed mechanically and standard patch clamp techniques are applied. Using these methods, spontaneously occurring and stimulus‐evoked inhibitory postsynaptic currents (IPSCs) were recorded from neurones in rat hippocampus at greatly improved resolution. In the presence of tetrodotoxin, to block presynaptic action potentials, spontaneous IPSCs seldom exceeded 25 pA. Evoked IPSCs elicited by constant electrical stimulation of a presynaptic neurone were larger and fluctuated in their amplitudes. Single‐channel currents, activated by the putative inhibitory transmitter γ‐aminobutyric acid (GABA), had a size of about 1 pA. The number of postsynaptic channels activated by a packet of inhibitory transmitter is probably not more than thirty, nearly two orders of magnitude smaller than previously reported estimates for CNS synapses. This might reflect matching of synaptic efficacy to the high input resistance of hippocampal neurones and could be a requirement for fine tuning of inhibition.
ATTENUATION OF THE ACUTE CARDIOVASCULAR RESPONSES TO HAEMORRHAGE BY TISSUE INJURY IN THE CONSCIOUS RAT
Authors: Little R. A. , Marshall H. W. , Kirkman E.
Published: December 2014

A moderate haemorrhage of 0·75 ± 0·09 ml (100 g body weight)−1 (11·1 ± 1·3% of estimated blood volume) in the conscious rat produces a tachycardia, possibly mediated by the baroreflex, which serves to maintain mean arterial blood pressure. A severe haemorrhage of 1〉 20 ± 0·06 ml (100 g)−1 (≥ 19·5 ± 1·5% of estimated blood volume) produces a bradycardia and mnarked hypotension. The bradycardia is reflex in nature and is due to an increased vagal efferent activity to the heart. This bradycardia is markedly attenuated in animals treated neonatally with capsaicin to render them deficient in C fibres, suggesting that peripheral C fibres (possibly cardiac C fibre afferents, Oberg & Thorén, 1972) are of importance in the bradycardic response to a severe haemorrhage. Concomitant tissue injury produced by bilateral hindlimb ischaemia in a group of animals with normal C fibre afferents markedly attenuates or abolishes the bradycardia and reduces the fall in mean arterial blood pressure produced by severe haemorrhage, although the tachycardia seen with smaller haemorrhages is affected to a much lesser degree. It is concluded that tissue injury can modify the cardiovascular response to a severe haemorrhage, possibly by interacting with the reflex effects of stimulating cardiac C fibre afferents.
KINETICS OF RAPID 45Ca UPTAKE INTO CHICK SKELETON IN VIVO: EFFECTS OF MICROWAVE FIXATION
Authors: Shaw A. J. , Whittaker G. , Dacke C. G.
Published: December 2014

We have investigated uptake kinetics for 45Ca labels acutely administered as single intravenous injections into twelve‐day‐old chicks in vivo. Effects of microwave fixation on this process have aJlso been studied. Rapid uptake of 45Ca was demonstrated into the skeleton with approximately 40% of injected label being found in the skeleton within the first 15 min. By 45 min tissue 45Ca levels had stabilized and showed little change during the following 90 min. Soft tissue isotope levels declined during the period from 3 to 135 min following injection. These data were obtained from animals in which tissue isotope levels were stabilized by fixation with microwaves at the point of killing by cervical dislocation. In animals where the microwave fixation step was omitted and tissues were dissected for counting at least 1 h after killing, 45Ca levels in both skeletal and soft tissues were 15‐20 % higher than in those from microwaved groups during the period 3‐15 min after injection. In a separate experiment, groups of chicks killed by cervical dislocation 3 min after isotope injection were fixed with microwaves at time intervals ranging from 0 to 45 min post‐mortem. Isotope levels in femur increased with time and were significantly higher in groups in which fixation was carried out 12 and 45 min after death when compared with those fixed at the point of death. Data in calvarium reflected those in femur but were not statistically significant at the time intervals tested. Estimates of unidirectional plasma‐bone Ca2+ influx (JPb 40Ca) into chick bone indicate high values for femur, 〉 1·64, µmol min‐1 (g wet weight)−1 and calvarium, 〉 1·26 µmol min−1 (g wet weight)−1, respectively. This suggests that Ca2+ is cleared very rapidly between blood plasma and exchangeable pools in the skeleton of the chick. Estimated JPb 40Ca values decline appreciably over short (15 min) time intervals, suggesting that significant backflux of the 45Ca marker occurs. These data collectively indicate that uptake of 45Ca into skeletal tissues occurs rapidly following its injection into chicks. 45Ca uptake continues for several minutes in the immediately post‐mortem animal and this process is reduced by microwave fixation. It is important to bear these factors in mind, when considering the effects of hormones and drugs on the uptake of bone‐seeking radionuclides.
THE EFFECT OF ALDOSE REDUCTASE INHIBITION ON THE PATTERN OF NERVE CONDUCTION DEFICITS IN DIABETIC RATS
Authors: Cameron N. E. , Cotter M. A. , Robertson S.
Published: December 2014

Conduction deficits caused by 2‐4 months diabetes were examined in one sensory and six motor nerve branches of mature rats. The effect of aldose reductase inhibitor (ponalrestat) treatment was assessed in preventative and reversal studies. The efficacy of 1% dietary myo‐inositol supplementation was also examined in a 2 month preventative group. Diabetes suppressed a maturation‐related increase in conduction velocity in the interosseus nerve supplying foot muscles. This was unaffected by any treatment. Large conduction velocity reductions (22‐29%) seen for fast nerves supplying four calf muscles and sensory saphenous nerves were prevented by ponalrestat treatment. In a reversal group, which had 2 months of diabetes followed by 2 months of treatment, restoration of conduction varied between nerves, ranging from 100% in sensory saphenous to 25% in soleus motor branches. Myo‐inositol supplementation had little effect. Sciatic nerves accumulated the sugar alcohol sorbitol with diabetes. This was markedly reduced by treatment, and correlated with the conduction velocity improvement. There was a 40% reduction in nerve free myo‐inositol levels after 2 months diabetes. Ponalrestat normalized myo‐inositol in the short term but failed to do so in 4 month preventative and reversal groups. Myo‐inositol treatment did not affect nerve levels. The data implicate the polyol pathway in the diabetic conduction velocity deficits seen in normally fast conducting motor and sensory nerves and suggest that aldose reductase inhibitor action does not depend on restoration of nerve myo‐inositol levels.
Kidney: a target organ for calcitonin gene‐related peptide
Authors: Zaidi M , Datta H , Bevis PJ
Published: December 2014

In the present study we have evaluated the effect of calcitonin gene‐related peptide (CGRP) on cyclic AMP levels in intact mouse kidneys. We have used an in vivo bioassay based on microwave irradiation as a means of rapid tissue fixation, followed by the determination of cyclic AMP concentration using a protein binding assay. CGRP was found to cause a dose‐dependent elevation of renal cyclic AMP levels, and despite being slightly less potent than calcitonin (CT), the action of CGRP was significantly more prolonged. The extended time course of action of CGRP is in sharp contrast to its known effect on bone cyclic AMP levels and could be of physiological relevance. CGRP may act on a receptor different from that of CT to produce distinct functional effects.
Analysis and presentation of intracellular measurements obtained with ion‐selective microelectrodes
Authors: Fry CH , Hall SK , Blatter LA , McGuigan JA
Published: December 2014

We have considered the manner in which data obtained with ion‐selective electrodes should be evaluated. The potential difference recorded by such electrodes, with respect to a stable reference, is converted to a concentration by a non‐linear transformation‐‐the Nernst or Nikolsky equation. The mean and standard deviation of such estimations of concentration are then usually presented, which assumes that the latter variable is normally distributed. If, however, the recorded potential difference (PD) is the normally distributed variable and the mean value calculated, then a different value of mean concentration will be obtained. We show here that the recorded PD is indeed the normally distributed variable using data from a variety of ion‐selective electrode measurements and conclude that the mean values of quoted ion concentrations have been overestimated by 6‐43%.
Actions of steroids and bemegride on the GABAA receptor of mouse spinal neurones in culture
Authors: Mistry DK , Cottrell GA
Published: December 2014

The effects of a synthetic and an endogenous steroid were studied on the GABAA receptors of isolated mouse spinal neurones, maintained in culture. Low doses of alphaxalone reversibly increased GABA‐evoked whole‐cell currents. Alphaxalone at higher doses (10‐50 microM), when pressure ejected onto spinal neurones, also directly evoked a membrane chloride current. Such currents were reversibly suppressed by bicuculline (a GABAA antagonist) and enhanced by phenobarbitone. 5 beta‐Pregnan‐3 alpha‐ol‐20‐one, a progesterone metabolite, dose‐dependently potentiated the amplitude of GABA‐evoked whole‐cell currents. The mechanism of potentiation was examined at the single‐channel level using outside‐out patches from spinal neurones. The main action of the steroid on the GABAA receptor appears to be similar to that found for barbiturates, in that they prolonged GABA‐activated bursts of channel openings. Bemegride had an antagonistic action on the GABAA receptor, suppressing both GABA‐ and pentobarbitone‐evoked whole‐cell currents to similar extents.
The effect of continued feeding of physiological amounts of lactose on the level of intestinal lactase and other disaccharidase enzyme activities in the rat
Authors: Tadesse K
Published: December 2014

Intestinal lactase activity in mammals is high at birth but begins to decline around weaning and reaches very low levels in adult life. The triggering mechanism for this decline is not clear. Because of the association of the decline with weaning, lack of lactose in the diet has been implicated. In 110 growing rats, the effect of continued supplementation of the diet after weaning with physiological amounts of either cows' milk or a 5% lactose solution on intestinal lactase and other disaccharidase enzyme activities was investigated. In both control and test animals, the specific lactase activity decreased from a peak value of 115 +/‐ 4 mumol min‐1 g‐1 protein before weaning to about 10% at maturity. There was no significant difference in the level or the pattern of decline between the groups. Sucrase, maltase and trehalase showed the normal maturational changes without being affected by the test diets. The finding suggests that diet, particularly the presence or absence of physiological amounts of lactose, has no appreciable effect on the age related spontaneous decline of intestinal lactase activity or on the pattern of development of the other disaccharidases.
Depression by fenoprofen of the rebound contractions' elicited by vagal stimulation and arterial infusion of ATP in the rabbit stomach in vivo
Authors: Baccari MC , Calamai F , Staderini G
Published: December 2014

In the atropine‐treated rabbit, vagal stimulation, arterial infusion of ATP or vasoactive intestinal peptide (VIP) caused gastric relaxation. At the end of either vagal stimulation or ATP infusion, but not after VIP, the gastric inhibitory responses were abruptly interrupted by ‘rebound contractions’. Administration of fenoprofen depressed or abolished the rebound contraction, thus transforming the brisk relaxant response, elicited by vagal stimulation or ATP, into long‐lasting relaxation. Indomethacin depressed the rebound contractions only at high doses and this effect was not always reproducible.
The involvement of the midbrain periaqueductal grey in the cardiovascular response to injury in the conscious and anaesthetized rat
Authors: Jones RO , Kirkman E , Little RA
Published: December 2014

Cell bodies within the periaqueductal grey (PAG) of the midbrain of the propofol‐anaesthetized rat were stimulated using the excitotoxin kainic acid. This resulted in a rise in arterial blood pressure and a tachycardia, together with a reduction in the sensitivity and a rightward resetting of the baroreflex. These changes mimicked the cardiovascular effect of bilateral hindlimb ischaemia in the rat. Further experiments in conscious rats indicated that electrolytic lesions in the PAG prevented the reduction in baroreflex sensitivity induced by limb ischaemia, but did not abolish the rightward resetting of the reflex or the pressor response and tachycardia when compared with sham‐lesioned controls. It is postulated that the PAG, a site of importance both in the integration of the defence reaction and the processing of afferent nociceptive information, may form part of a pathway involved in the reduction of the sensitivity of the baroreflex following injury. This pathway is suggested to be separate from a second, as yet undefined, pathway mediating the baroreflex resetting and pressor responses associated with injury.
Effects of phorbol ester and related compounds on acetylcholine‐evoked [3H]leucine‐labelled protein secretion in permeabilized rat pancreatic acini
Authors: Francis LP , Singh J
Published: December 2014

The effects of the phorbol ester, 12‐tetradecanoyl‐phorbol‐13‐acetate (TPA) and related compounds on acetylcholine (ACh)‐evoked [3H]leucine‐labelled protein release (secretion) were tested in isolated permeabilized rat pancreatic acini. The aim was to determine whether the diacylglycerol‐like compounds can still potentiate the actions of ACh during unfluctuating supramaximal elevation of cytosolic free calcium (Ca2+) levels. TPA and R59022, an inhibitor of diacylglycerol kinase, evoked marked biphasic dose‐dependent increases in 3H‐labelled protein secretion from permeabilized rat pancreatic acini. Synthetic diacylglycerol (OAG) and 8‐bromo cyclic GMP elicited small increases in 3H‐labelled protein release while an inactive phorbol ester (4 alpha‐phorbol‐12,13‐didecanoate; 4 alpha‐PDD) and polymyxin B, an inhibitor of protein kinase C, were unable to stimulate secretion. Combining polymyxin B with TPA resulted in an inhibition of 3H‐labelled protein secretion. Acetylcholine also induced a dose‐dependent increase in 3H‐labelled protein output, but when TPA or R59022 was combined with ACh, there was a marked potentiation of the ACh‐evoked secretory response, particularly at higher concentrations of ACh. This synergism was unaffected by the protein kinase C inhibitor, polymyxin B. The results show that cytosolic free Ca2+ and protein kinase C may not be the only mediators of ACh‐evoked secretion. Moreover, they indicate that protein kinase C may not be involved in the potentiation by TPA of ACh‐evoked 3H‐labelled protein release.
Effects of Ca2+ channel agonist‐antagonist enantiomers of dihydropyridine 202791 on insulin release, 45Ca uptake and electrical activity in isolated pancreatic islets
Authors: Boschero AC , Carroll PB , De Souza C , Atwater I
Published: December 2014

This is the first study using the selective agonist/antagonist stereoisomers of dihydropyridine 202791 to investigate stimulus‐secretion coupling in pancreatic islet cells. We studied effects of the (+)(Ca2+ channel agonist) and (‐)(Ca2+ channel antagonist) forms of the dihydropyridine, on 45calcium net uptake, insulin secretion, and membrane potential measured in rodent islets. The antagonist partially inhibited glucose‐induced insulin secretion and Ca2+ uptake; however, the potassium‐induced Ca2+ uptake was completely inhibited. The antagonist did not completely block glucose‐evoked spike activity. Addition of the agonist enhanced insulin release and Ca2+ uptake in the presence of 5.6 mM‐glucose, but did not increase insulin release or Ca2+ uptake in 16.7 mM‐glucose. In the presence of tetraethylammonium (TEA), (+)202791 increased and (‐)202791 decreased the duration of glucose‐induced action potentials. The results again confirm the presence of a dihydropyridine‐sensitive Ca2+ channel in pancreatic B‐cells. In addition these data suggest that in these cells there is activation of a dihydropyridine‐insensitive Ca2+ entry in the presence of glucose.
Neuropeptides and disuse of the rat parotid gland
Authors: Mansson B , Ekman R , Hakanson R , Ekstrom J
Published: December 2014

Rats were fed a liquid diet with the aim of decreasing nervous reflex activity in the parotid glands. In rats killed after 21 days on this diet the glands were atrophied and the total amounts of the neuropeptides, substance P, vasoactive intestinal peptide and calcitonin gene‐related peptide, were lower than in control glands.
Role of histamine receptors in rabbit pancreatic exocrine secretion stimulated by cholecystokinin and secretin
Authors: Pariente JA , Madrid JA , Salido GM
Published: December 2014

An investigation was made of the effects of H1 and H2 receptor agonists and antagonists on rabbit pancreatic exocrine secretion stimulated by secretin and cholecystokinin (CCK). The H1 agonist 2‐thiazolylethylamine elicited dose‐dependent increases in the rate of secretion. Increases in pancreatic juice flow and enzyme output were also noted after H2 antagonist cimetidine. In contrast, the H1 antagonist chlorpheniramine and H2 agonist dimaprit caused reductions in flow and enzyme output. The results suggest that H1 receptors have stimulative effects and H2 receptors have inhibitory effects on exocrine rabbit pancreas.
Factors influencing the movement of parotid amylase into the serum of rats on feeding
Authors: Proctor GB , Asking B , Garrett
Published: December 2014

Feeding hard chow to rats for 1 h caused an increase in parotid‐type amylase in the serum. The increase was largely inhibited by parasympathetic or sympathetic denervation of the parotid glands and also by beta‐adrenoceptor blockade. The results suggest that movement of amylase into the blood is influenced not only by the volume of saliva being formed but also by its amylase content.
Histidine‐stimulated acid secretion in the conscious rat is mediated by amino acid uptake system N
Authors: Dimaline R , Wilkinson M , Talbot SJ
Published: December 2014

The characteristics of sodium‐dependent, histidine‐stimulated gastric acid secretion were studied in the conscious gastric‐fistulated rat. Intragastric L‐histidine, but not glutamine, asparagine, glutamic acid or glycine, stimulated acid secretion. The histidine‐stimulated acid secretion was inhibited by the presence of glutamine or asparagine, but not by glutamic acid or glycine. The substitution of lithium for sodium in the gastric perfusate was tolerated. Together with previous data, the results indicate that an N‐like amino acid uptake system mediates histidine‐stimulated acid secretion in the conscious rat.
Separation of tubular electrical activity in amphibian skeletal muscle through temperature change
Authors: Padmanabhan N , Huang CL
Published: December 2014

The effect of temperature on the form of the propagated action potential was investigated in frog skeletal muscle fibres. Increasing the temperature decreased the duration of the initial overshoot but a hump then appeared during a more prominent after‐depolarization. Finally, at 28‐30 degrees C, the after‐depolarization was either noticeably enlarged or entirely absent. This all‐or‐none failure of tubular conduction suggests that excitation of the tubular membrane takes place through regenerative activity rather than graded electrotonic spread of depolarization. However, it is consistent with a partial electrical isolation of the tubular lumina, possibly through the access resistance proposed in earlier theoretical models for muscle membrane.
Fourier analysis of the relation between the discharge of quadriceps motor units and periodic mechanical stimulation of cat knee joint receptors
Authors: Ferrell WR  , Rosenberg  , Baxendale RH , Halliday D , Wood L
Published: December 2014

It has been widely assumed that joint receptors contribute to the reflex regulation of movement and posture, although there have been few clear demonstrations of joint‐mediated reflex actions on alpha‐motoneurones other than those attributable to flexor reflex afferents. The present study extends our recent work on joint‐mediated reflexes by using Fourier analysis of spike train interactions to demonstrate that restricted mechanical activation of a small number (one to five) of knee joint receptors by localized indentation of the joint capsule can modify the firing pattern of quadriceps motoneurones in decerebrated cats. The modulation of this discharge pattern can be reversibly abolished by application of droplets of lignocaine directly to the joint nerve and consequently can be attributed unambiguously to articular afferents. Activation of single joint afferents could on occasion produce changes in motor unit firing patterns, but usually activation of two or more was required before secure effects were observed. Increasing the intensity of indentation (resulting in activation of greater numbers of joint receptors) increases the strength of coupling between joint afferent input and motor unit responses, although the relationship is not linear. The relation between the discharge patterns of pairs of motor units was also examined, and it was found that significant coupling occurred at the stimulus frequency, superimposed on a ‘background’ coupling from unidentified sources. The phase relationship between pairs of motor units was not affected by the periodic stimulus. However, it was observed that if two motor units were firing independently of one another in the absence of capsule probing, maintained capsular indentation produced a striking synchronization between the discharges of the two motor units. These experiments show strong joint‐mediated reflex effects on motor unit firing indicating that joint receptors may have an important role to play in motor control.
The intracellular concentration of free magnesium in extensor digitorum longus muscles of the rat
Authors: MacDermott M
Published: December 2014

Magnesium‐sensitive microelectrodes were used to measure the intracellular concentration of free Mg2+, [Mg2+]f, in rat extensor digitorum longus muscles in vitro at 30 degrees C. The intracellular activities of Na+ and K+ were also determined so that allowance could be made for the interference from these ions with the Mg2+ electrode response. The mean value for [Mg2+]f based on twenty‐six measurements in twelve muscles was 0.47 mM.
The localization of somatostatin‐like immunoreactivity in the alimentary tract of the sheep with observations on the effect of an infection with the parasite Haemonchus contortus
Authors: Vergara-Esteras P , Harrison FA , Brown D
Published: December 2014

Cells containing somatostatin immunoreactivity were localized in the alimentary tract of parasite‐free sheep by indirect immunocytochemistry, using an antiserum raised to ovine somatostatin. Nerve fibres showing somatostatin‐like immunoreactivity were identified in the oesophagus, reticulum wall and groove, rumen pillar and wall, omasum sulcus and abomasum. Varicose fibres were found in the myenteric plexuses of the duodenum, jejunum, ileum and colon. The greatest distribution of endocrine cells (99 cells mm‐2) was found in the antrum of the abomasum with 47, 29, 12 and 6 cells mm‐2 respectively in the fundus, the first part of the duodenum, mid‐jejunum and ileum. Some of the parasite‐free sheep which had never experienced infection with larvae of the abomasal nematode, Haemonchus contortus, were paired with similar sheep in an experiment to investigate the effect of parasitism on nitrogen metabolism in the small intestine. The protocol of this experiment required observations before and after parasite infection, with final observations 2 weeks after removal of the infection by treatment with an anthelmintic drug. The sheep were then killed and tissues taken from each paired animal. Tissues from the recently parasitized sheep showed increases of D cells in the fundus and antrum of the abomasum. At present it is not clear if these increases were related to parasitism, per se, or were the post‐treatment indicators of healing and recovery from infection with parasite larvae.
Assessment of bone turnover in the dry period of dairy cows by measurement of plasma bone GLA protein, total plasma alkaline phosphatase activity and urinary hydroxyproline
Authors: van Mosel M , Corlett SC
Published: December 2014

Plasma osteocalcin, or plasma bone GLA protein (BGP), total plasma alkaline phosphatase activity and urinary hydroxyproline excretion of twenty‐four pregnant dairy cows (thirteen in their first or second pregnancy, i.e. low parity, and eleven in their third or more pregnancies, i.e. high parity) were measured from 7 weeks before parturition until 1 week after parturition. Seven weeks before parturition the cows' ration was changed to one containing either 0.22% magnesium (low magnesium, LMg) or 0.82% magnesium (high magnesium, HMg) in the dry matter, and the potassium content of both rations was increased to approximately 4.1% in the dry matter to reduce the absorption of magnesium. Plasma BGP levels decreased significantly (P less than 0.01) as parturition approached while total plasma alkaline phosphatase activity and urinary hydroxyproline excretion did not. Magnesium supply and parity had no significant effect on this decrease. The overall plasma concentration of BGP, total plasma alkaline phosphatase activity and the urinary hydroxyproline/creatinine ratio in the prepartum period were affected by parity (P less than 0.05) with higher values in the lower parity cows. A significant positive correlation (r = 0.58, P less than 0.01) was found in all cows between plasma BGP level at parturition and the percentage of the bone surface covered with osteoblasts; however, plasma BGP was not correlated either with other histomorphometric variables or with total alkaline phosphatase activity during this time.
The G. L. Brown lecture. Adventures in anaesthesia
Authors: Angel A
Published: December 2014

The results presented in this lecture show that anaesthetic agents impede the transfer of information from the periphery to the cerebral cortex. This is shown both as a reduction in the amplitudes of the initial positive and negative waves of the cerebral cortical response evoked by simulation of the periphery and as an increase in the latency of this response. This effect is most probably a prime effect of anaesthesia since (a) it is common to all the anaesthetics used, (b) the potency of the anaesthetics is directly proportional to their lipid solubility, and (c) the effect is reversed by high ambient pressures. The major site at which information transfer is most susceptible to the action of anaesthetics is at the level of the ventrobasal thalamus, although the cells in cortical layer V also appear to have an enhanced susceptibility to anaesthetic action. This latter observation is seen both in whole animal and cortical slice preparations. None the less, the first site of synaptic transfer at which anaesthetics exert a profound effect is upon the monosynaptically generated responses of ventrobasal thalamic neurones to cuneothalamic input. A possible mechanism of action for anaesthetic agents acting at this site would be upon a hypothetical cortico‐thalamic‐reticular‐thalamic loop with the theoretical ability to control the responsiveness of the ventrobasal thalamic cells. This action was proposed both from the activity of neurones in response to anaesthetic agents and the anatomical arrangement seen in the thalamus. The thalamic reticular nucleus is a curved sheath of cells situated between the internal capsule and the external medullary lamina, capping and bounding laterally the specific nuclei of the dorsal thalamus. There is both anatomical and physiological evidence that the thalamic reticular nucleus comprises part of the thalamic reticular formation: its cellular structure also resembles that of the brain stem regions of the reticular formation (Ramon‐Moliner, 1975). Early degeneration and Golgi studies showed that ascending fibres from the medial parts of the pontine and mesencephalic components of the brain stem reticular formation innervated the thalamic reticular nucleus ventrally, by penetrating the zona incerta, and dorsally, via the intralaminar and dorsal thalamic nuclei (Scheibel & Scheibel, 1958). These observations have been confirmed and extended more recently and it appears that the major innervation of the thalamic reticular nucleus occurs via the ventral route which follows the entire course of the reticular nucleus. No fibres ascending from the dorsal column lemniscal system, the spino‐cervico‐lemniscal system or the spinothalamic tract have been observed to terminate within the thalamic reticular nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)
The effects of midlumbar spinal cord section on opioidergic modulation of the sural‐gastrocnemius reflex of the rabbit
Authors: Clarke RW
Published: December 2014

In decerebrated rabbits spinalized at the thoraco‐lumbar junction, crushing the spinal cord between segments L4 and L5 resulted in enhancement of the sural‐gastrocnemius reflex. After midlumbar crush, naloxone increased the reflex response to significantly greater levels than observed in earlier experiments in rabbits with only a low thoracic spinal section. Naloxone‐reversible, stimulus‐evoked inhibition of the reflex response was not affected by midlumbar crush. These findings show that neurones in midlumbar segments of the spinal cord do not contribute to opioidergic modulation of the sural‐gastrocnemius reflex.
Renal clearance of plasma allantoin in sheep
Authors: Chen XB , Kyle DJ , Orskov ER , Hovell FD
Published: December 2014

The recovery in urine of an intrajugular infusion of physiological amounts of allantoin was measured in four sheep nourished by an intragastric infusion of volatile fatty acids and casein (to eliminate rumen fermentation). The recovery was 72% (S.E.M. 7) and the remainder was presumed to have been lost by diffusion into the gut and degradation by gut microflora. Measured in two sheep, allantoin was removed from the blood at a fractional rate of 0.30 h‐1, and excreted in urine at 0.23 h‐1. Calculation based on creatinine excretion showed glomerular filtration rate and tubular reabsorption of allantoin to be unchanged by the intravenous infusion. Maximal tubular reabsorption at 1.28 mmol day‐1 was saturated by the load of endogenous allantoin alone. In a second experiment with seven normally fed sheep (28‐50 kg live weight, all given 1 kg feed), urinary excretion and plasma concentration of allantoin were linearly related. However, the errors were such that plasma allantoin concentration would be of little value as a predictor of urinary excretion. There was a nearly twofold range in allantoin excretion (the larger animals excreting less), which implied that the supply of microbial biomass to the host animal per unit of feed ingested could be profoundly affected by feeding level.
The relationships between glucose absorption and insulin secretion and the migrating myoelectric complex in the pig
Authors: Rayner DV
Published: December 2014

Net glucose and free amino nitrogen absorption and insulin output in the pig hepatic portal vein were calculated from portal‐arterial concentration differences and portal blood flow measured by thermodilution. Duodenal and jejunal motility were assessed by electromyography. In the fed pig, the migrating myoelectric complex (MMC) pattern of motility persisted; glucose and amino nitrogen absorption and insulin secretion all varied with the phase of the MMC, rising to maximum values 19.4 +/‐ 3.1 min before and falling to minimum values 16.7 +/‐ 4.4 min after phase III. The variations in glucose absorption with the MMC were caused primarily by changes in duodenal and jejunal motility rather than by changes in the rate of gastric emptying as glucose absorption and insulin secretion varied with the phase of the MMC during duodenal glucose infusions, with maximum values occurring 24.4 +/‐ 3.3 min before and minimum values 14.9 +/‐ 2.5 min after phase III activity. The mean glucose absorption time calculated by timing the appearance of glucose in the portal vein following an intraduodenal bolus injection was significantly longer when given in phase I showing that absorption was less rapid when the intestine was not contracting. A significant amount of glucose is metabolized by intestine, as during glucose infusion (500 mg min‐1) the average portal glucose absorption (376 mg min‐1) was less than the glucose infused.
Urea degradation in sheep nourished by intragastric infusion: effects of level and nature of energy inputs
Authors: Whitelaw FG , Milne JS
Published: December 2014

Four female sheep nourished wholly by infusions of volatile fatty acids (VFA), buffer and minerals to the rumen and casein to the abomasum were given in addition infusions of supplementary energy calculated to increase the energy input to the rumen by 30%. The design was a Latin square and the supplements given were (a) nil, (b) a standard VFA mixture similar to the basal infusion, (c) butyric acid alone and (d) glucose. Measurements were made of nitrogen retention and rumen fermentation characteristics and the kinetics of urea metabolism were measured over 24 h by means of a single injection of [14C]urea. An active microbial fermentation was established in the rumen in response to the infusion of glucose and estimates of microbial protein synthesis derived from urinary purine excretion agreed well with those calculated from stoichiometric principles. The presence of a microbial population in the rumen resulted in a decrease in urinary urea excretion and reductions in plasma urea concentration, urea pool size and rumen ammonia (NH3) concentration. Infusion of the mixed VFA or butyric acid supplements had no effect on these indices of urea metabolism. Measurements of urea irreversible loss rate showed high variability and the mean values did not differ significantly between the four treatments. Urea degradation in the gastrointestinal tract was also highly variable but increased, on average, by 2.4 g day‐1 on the high‐energy treatments. Examination of regression relationships between these variables also indicated a difference between the glucose treatment and the others in the metabolic fate of the NH3 derived from urea hydrolysis. It is concluded that urea degradation increased in response to additions of energy but did not differ according to the nature of the supplements supplied. In the glucose‐supplemented group, the NH3 arising from degraded urea was incorporated into microbial protein and so removed from the urea‐NH3 cycle; when additions of mixed VFA or butyric acid were given, the NH3 arising in hydrolysis appeared simply to be reabsorbed as NH3 and to contribute anew to urea formation.