bluuebunny/crossref_metadata_2025 huggingface dataset:
A COMPARISON OF ENERGY METABOLISM IN THE NEW‐BORN INFANT, PIGLET AND LAMB
Authors: Mellor D. J. , Cockburn F.
Published: December 2014

Characteristics of energy metabolism in the new‐born infant, piglet and lamb have been compared quantitatively in order to assess how the constraints imposed by the availabilities of energy substrates in body reserves and colostrum differ between species and affect the new‐born's well being during the first day after birth. Three air temperature ranges, described as thermoneutral (32‐38 °C), moderate (18‐26 °C) and cold (0‐10 °C) and representing the usual birth environments of infants, piglets and lambs, respectively, have been considered. The analysis revealed the following noteworthy points. Carbohydrate and lipid are the major energy substrates for heat production because protein catabolism is minimal during the first day after birth in all three species. The availability of carbohydrate determines how long the new‐born can avoid hypoglycaemia, which threatens well being because it leads to hypothermia or compromised cerebral function, but lipid availability can affect the periods for which the carbohydrate can last. Thus, in unfed piglets and lambs the available reserves of liver and skeletal muscle glycogen (g/kg body weight) are similar in normal (n.) and growth retarded (g.r.) individuals, but glycogen exhaustion occurs earlier in g.r. new‐borns because a reduced lipid availability in them increases their dependence on carbohydrate. In contrast, lipid energy is plentiful in g.r., preterm (p.) and n. infants, so that the faster depletion of glycogen in g.r./p. than in n. individuals is primarily due to a restricted prenatal glycogen deposition in the former. The usual colostrum intakes of n. infants are very low during the first day, but their body reserves can supply the required energy, the major source of carbohydrate being liver glycogen. However, g.r./p. infants require supplementary feeding, the choice of feed being determined by factors such as the intakes the infants can achieve, the carbohydrate content of the feed and the need to ensure a balanced supply of minerals, electrolytes and other substances. In their usual birth environments piglets and lambs, whether growth retarded or not, require colostrum to avoid hypothermia during the first day. The colostrum of both species is rich in lipid, which corrects any deficit in the new‐born and thus extends the availability of glycogen, but at the usual colostrum intakes the amounts of lactose can provide sufficient carbohydrate energy for only about half a day. Piglets and lambs, even when fed fully, are therefore obliged to call on their body glycogen reserves in order to make up the difference. After the first day in all three species milk must rapidly become the only source of carbohydrate, lipid and protein. It is suggested that despite differences between them, the piglet or lamb could prove to be useful animal models of the infant's metabolism, but only if the experimental conditions are chosen carefully.
IMMUNOCYTOCHEMICAL LOCALIZATION OF GASTRIC INHIBITORY PEPTIDE AND GLUCAGON IN THE ALIMENTARY TRACT OF RUMINANTS
Authors: Bunnett N. W. , Harrison F. A.
Published: December 2014

Cells containing gastric inhibitory peptide (GIP) and glucagon immunoreactivity were localized in the alimentary tract of the adult sheep, young lamb, calf and goat kid by indirect immunocytochemistry, using antisera raised to the porcine peptides. GIP and glucagon were localized in two distinct cell populations. Cells containing immunoreactive GIP were confined to the mucosa of the duodenum, jejunum and ileum and were not observed in the forestomachs, abomasum, large intestine and pancreas. Cells containing immunoreactive glucagon were distributed widely throughout the alimentary tract but were most numerous in the pancreatic islets and the ileum. Neither GIP nor glucagon‐containing cells were observed in the forestomachs. The distribution of the peptides was similar in adult and young animals. Both cell types appeared to possess an apical projection into the glandular lumen of the alimentary tract. Pre‐absorption of the primary antisera with the appropriate peptide antigen abolished the staining.
ALTERATION OF LACTASE AND AMINOPEPTIDASE N EXPRESSION IN PORCINE ENTEROCYTES BY ENERGY INTAKE AND ENVIRONMENT
Authors: Dauncey M. J. , Ingram D. L.
Published: December 2014

The influence of nutrition, environmental temperature and time of feeding on lactase and aminopeptidase N activities in enterocytes of young pigs has been investigated. Animals were kept in the cold (10 °C) or warm (35 °C) and given either a high or low energy intake. In animals from the cold, lactase activity as determined by scanning microdensitometry was significantly lower at 4 h after a meal than it was in animals from the warm. At 6 h, the activities were similar in all groups, while at 20‐24 h after feeding, lactase activity was much greater in those kept at 10 °C than in those at 35 °C. Level of energy intake had no statistically significant effect and no differences were found with respect to aminopeptidase N. The possibility that these differences in lactase activity are related to thyroid hormone metabolism and energy supply in relation to demand is discussed.
RELATIVELY HIGH BILIARY SECRETORY MAXIMUM FOR NON‐MICELLE‐FORMING BILE ACID: POSSIBLE SIGNIFICANCE FOR MECHANISM OF SECRETION
Authors: O'Máille E. R. L. , Hofmann Alan F.
Published: December 2014

Because of the formation of mixed micelles, the effective (i.e. monomeric, intermicellar) concentration of bile acid in bile is only a small fraction of the total concentration: this factor could be of critical importance for the net hepatic transport of the natural bile acids (especially transport across the canalicular membrane, which is hypothesized to be passive). To assess the influence of micelle formation on bile acid secretion, the rate‐limiting canalicular transport of the natural, micelle‐forming bile acid, cholyltaurine, was compared with that of the artificial non‐micelle‐forming bile acid, dehydrocholyltaurine (which undergoes partial reductive metabolism), in the anaesthetized rat with a bile fistula. The derivatives of dehydrocholyltaurine shared the same biliary transport system as cholyltaurine and had a secretory maximum ( 22 ± 4·7 (S.D.) µmol/min. kg, n = 12) which was significantly greater than that of cholyltaurine (15 ± 1·2, n = 6) (P 〈 0·01). The biliary secretion rates of phospholipid and cholesterol during maximal secretion of dehydrocholyltaurine derivatives were not raised over control values; 3α‐hydroxy,7,12‐dioxocholanoate (the taurine conjugate of which accounted for about 70‐80% of the total bile acid in bile during dehydrocholyltaurine infusion) has also been shown in vitro to be non‐micelle forming. These results would seem to indicate that micelle formation in bile is not essential for the effective net translocation of bile acid by the specific canalicular membrane carriers. The high maximal velocity with which dehydrocholyltaurine derivatives were secreted in the face of a bile acid activity in bile of one to two orders of magnitude greater than the intermicellar concentration of cholyltaurine suggests that an active transport system for bile acids may be located at the canalicular membrane.
MEASUREMENT OF BLOOD FLOW AND LIPOLYSIS IN THE HINDQUARTER TISSUES OF THE FAT‐TAILED SHEEP IN VIVO
Authors: Gooden J. M. , Campbell S. L. , Van Der Walt J. G.
Published: December 2014

Karakul and Namaqua‐Afrikander sheep, both of which are fat‐tailed breeds, were examined for suitability as models for studying lipid metabolism in vivo. The anatomy of the blood supply to the hindquarters of both breeds was examined, and a technique developed for sampling the venous outflow from the fat tail. The composition of the tail and the rest of the hindquarters was determined and found to be similar in both breeds. The hindquarters contained 35% fat, about half of which was located in the tail (72‐74% fat). Rates of blood flow through the whole hindquarters, tail adipose tissue and leg muscle of Karakul ewes were measured. Tritiated water (TOH) was used for measurement of specific blood flow and p‐aminohippuric acid (PAH) for measurement of absolute blood flow. The specific blood flow rate for tail adipose tissue was 3·62 ± 0·12 ml.min−1.100 g−1 and absolute blood flow was estimated as 74 ± 7 ml.min‐1. The absolute flow through the rest of the adipose tissue in the hindquarters was similar to that flowing through the tail, and together they represented about 15% of the total absolute flow through the whole hindquarters, 794 ± 131 ml.min−1 measured directly using PAH. Total blood flow through the hindquarters estimated from the specific flow rate (using TOH) and the mass of the hindquarters was 761 ± 50 ml.min−1. The absolute blood flow through the hindquarters of Namaqua‐Afrikander ewes (626 ± 39 ml.min−1) was lower than that measured in the Karakul ewes, but the difference was not significant (P 〉 0·10). The rates of net release from tail adipose tissue of Karakul ewes measured in vivo were 3·0 ± 0·6 and 2·0 ± 0·2 µmol.min−1. 100 g−1 for free fatty acids and glycerol respectively. Intravenous infusion of noradrenaline (2µg.min−1.kg−1 liveweight) increased venoarterial differences of both free fatty acids and glycerol 2‐ to 3‐fold and blood flow increased by about 60%. As a result, in response to noradrenaline, net releases for both free fatty acids and glycerol increased 4‐fold.
THE EFFECT ON THE EFFERENT VAGAL NERVES TO THE HEART OF STIMULATING ATRIAL RECEPTORS IN THE DOG
Authors: Walters G. E. , Mary D. A. S. G.
Published: December 2014

In chloralose‐anaesthetized dogs, distension of small balloons at the pulmonary vein‐atrial junctions to stimulate atrial receptors with myelinated vagal afferent nerves causes an increase in heart rate but does not influence the activity in efferent vagal cardiac nerves. However, distension of these small balloons also stimulates atrial receptors with non‐myelinated vagal and sympathetic afferent nerves, which are thought to affect the heart rate and activity in efferent vagal cardiac nerves. In the present investigation, seven dogs anaesthetized with chloralose were studied by distension of small balloons at the pulmonary vein‐atrial junctions and in the left atrial appendage, and by graded cooling of the vagal nerves in the neck; cooling to 9 °C was used to prevent the increase in activity in myelinated vagal afferent nerves to distension of the small balloons and cooling to 0 °C was used to prevent responses to the distension in all vagal afferent nerves. Eleven vagal efferent nerve fibres were studied which responded to stimulation of carotid baroreceptors and chemoreceptors. Distension of the small balloons did not affect the activity in these eleven efferent vagal nerve fibres, with the vagi at 37 °C or during vagal cooling to 9 °C or to 0 °C. The results indicate that upon distension of the small balloons, none of the three types of atrial receptor influence the activity in efferent vagal cardiac nerves. The results support the conclusion that stimulation of atrial receptors with myelinated vagal afferent nerves, responsible for the reflex increase in heart rate, does not influence the activity in efferent vagal cardiac nerves.
EFFECT OF VERATRIDINE INJECTED INTO THE AORTIC ROOT ON RESISTANCE AND CAPACITANCE IN THE ABDOMINAL CIRCULATION IN ANAESTHETIZED DOGS
Authors: Hainsworth R. , McGregor K. H. , Ford R.
Published: December 2014

In dogs anaesthetized with chloralose, cardiac receptors were stimulated by injections of veratridine into the aortic root and the effects studied on resistance and capacitance in the vascularly isolated and perfused abdominal circulation. Unless carotid sinus pressure was high, veratridine injections consistently resulted in dilatation of resistance and capacitance vessels. However, at high carotid pressures, the resistance response to veratridine was inhibited and the capacitance response was usually reversed. These results indicate that stimulation of cardiac receptors can affect resistance and capacitance in the abdominal circulation. Further experiments are required to evaluate the physiological role of these responses.
RETROGRADE INFUSION OF BLOOD INTO A PULMONARY VEIN PROMOTES NATRIURESIS IN ANAESTHETIZED DOGS
Authors: Sutton P. M. I. , Abed J. S. M. , Nashat F. S.
Published: December 2014

Retrograde infusion of blood into a pulmonary vein raised the pressure by 0·5‐1 kPa in the cannulated vein. There were no changes in heart rate, arterial blood pressure, left atrial pressure, right atrial pressure or the pressure in the other pulmonary veins. The rise in pulmonary venous pressure was associated with an increase in urinary sodium concentration and excretion. However, there was no change in urine volume. The natriuresis was abolished by cooling the vagi to 9 °C. It is argued that receptors up‐stream in the pulmonary veins themselves may be involved in the increase in sodium excretion that follows a rise in left atrial pressure.
THE DISTRIBUTION OF VASOACTIVE INTESTINAL POLYPEPTIDE‐LIKE, SUBSTANCE P‐LIKE AND BOMBESIN‐LIKE IMMUNOREACTIVITY IN THE DIGESTIVE SYSTEM OF THE SHEEP
Authors: Wathuta E. M.
Published: December 2014

Peptides which are possibly related to the non‐cholinergic, non‐adrenergic division of the autonomic nervous system have been identified by immunofluorescence in the digestive system of mature sheep. Vasoactive intestinal polypeptide‐, substance P‐, and bombesin‐like immunoreactivity were localized in neural elements throughout the ovine gastrointestinal tract (g.i.t.). Vasoactive intestinal polypeptide‐like immunoreactivity (VIP‐l.i.) was demonstrable in the submaxillary, parotid and the sublingual salivary glands close to small blood vessels and the acini. VIP‐l.i. was also demonstrable in the upper oesophagus in connective tissue near small blood vessels. In the forestomachs, abomasum, and small and large intestines reactive fibres were present in the mucosa, submucosa, smooth muscle layers and the plexuses. The plexuses also contained reactive nerve cell bodies. VIP‐reactive fibres were found in the pancreas, the gall bladder and the common bile and pancreatic duct but were not found in the intestinal mesentery, portal vein, and liver tissue. Substance P‐like immunoreactivity (SP‐l.i.) was demonstrable in nerve fibres in all the layers of the g.i.t. and in nerve cell bodies in the gut plexuses. The pancreas and the gall bladder also contained a few scattered fibres. Additionally, SP‐l.i. was present in open‐type endocrine cells throughout the mucosa of the small and large intestines but no SP‐l.i. was found in the salivary glands or the oesophagus. Bombesin‐like immunoreactivity (B‐l.i.) was associated with nerve fibres and was demonstrable in the mucosa and myenteric plexuses throughout the g.i.t. B‐l.i. in the smooth muscle appeared to be restricted to nerve fibres in the forestomachs, the abomasum, and the upper small intestine. No B‐l.i. was found in the salivary glands, oesophagus, liver tissue, pancreas, gall bladder or intestinal mesentery.
THE EFFECT OF HYPERINSULINAEMIA ON GLUCOSE UTILIZATION AND OXIDATION AND ON OXYGEN CONSUMPTION IN THE FETAL LAMB
Authors: Hay William W. , Meznarich Huei Kang
Published: December 2014

In order to measure the effect of hyperinsulinaemia on fetal glucose metabolism and oxygen consumption, we applied the glucose‐clamp technique to experiments in fifteen late‐gestation, unstressed, chronically catheterized fetal lambs. In a control period, and immediately thereafter following 2 h of hyperinsulinaemia, we measured fetal glucose utilization and oxidation rates (radioactive tracer methodology) and net fetal uptake rates of exogenous glucose and oxygen uptake rates (Fick principle). During the period of hyperinsulinaemia, fetal glucose concentration was maintained at the average control period value by a variable rate of glucose infusion into the fetus in response to serial 10 min measurements of fetal arterial blood glucose concentration. Hyperinsulinaemia in the fetus (12·12 ± 1·92 ng.ml−1 (mean ± S.E.M.) arterial plasma) resulted in a 13% increase in net fetal oxygen uptake rate (0·310 ± 0·011 to 0·349 ± 0·012 mmol.min−1.kg−1), a 106% increase of fetal glucose uptake rate (4·54 ± 0·43 to 9·35 ± 0·50 mg.min−1.kg−1) and an 83% increase of fetal glucose utilization rate (4·94 ± 0·43 to 9·05 ± 0·83 mg.min−1.kg−1). Fetal glucose uptake and utilization rates were not different from each other during the control and the hyperinsulinaemia periods. The fraction of glucose that was oxidized (0·58 ± 0·05, control; 0·54 ± 0·05, hyperinsulinaemia) did not change significantly; thus the glucose oxidation rate, the rate of entry of glucose into non‐oxidative pathways, and the amount of oxygen used for glucose oxidation all increased in proportion to glucose utilization. These results suggest that insulin promotes the entry of glucose into fetal tissues, thereby increasing fetal glucose utilization and oxidation rates and substituting glucose oxidation for that of other substrates. The insulin‐enhanced glucose utilization rate also increases slightly fetal metabolic rate.
INTRACELLULAR AND WHOLE‐CELL RECORDINGS FROM ZONA‐FREE HAMSTER EGGS: SIGNIFICANCE OF LEAK IMPALEMENT ARTIFACT
Authors: Georgiou P. , Bountra C. , House C. R.
Published: December 2014

Measurements have been made of membrane potential and input resistance of zona‐free hamster eggs from single micro‐electrode recordings. At room temperature (20‐23 °C) the mean (±S.D.) values for the potential and resistance were ‐30 ± 8 mV and 280 ± 130 MC (n = 94 eggs). At 37 °C the mean (±S.D.) values for the potential and resistance were ‐39 ± 13 mV and 230 ± 60 MΩ (n = 60 eggs). The most negative potential recorded at room temperature was ‐51 mV in a cell which had an input resistance of 620 MΩ. At 37 °C six eggs out of sixty had potentials more negative than ‐50 mV and three of these gave all‐or‐none action potentials in response to depolarizing current pulses. In a separate series of experiments with high resistance micro‐electrodes (ca1. 100 MΩ) six eggs out of twenty‐one had potentials more negative than ‐50 mV and four of these were electrically excitable. Transient potential recordings during impalement indicated that the potential was more negative than ‐30 mV but that the insertion of a micro‐electrode produced a leak pathway with a resistance of about 10 MΩ, substantially smaller than the steady‐state estimates of the input resistance (see above). Whole‐cell recordings with patch pipettes gave potentials in the range ‐30 to ‐80 mV and input resistances in the range 180 to 350 MΩ (n = 8); four eggs gave action potentials in response to depolarizing current pulses passed through the patch pipette. It is concluded that the leak impalement artifact is so significant in micro‐electrode recordings from hamster eggs that it prevents routine reliable potential measurements.
THE ONTOGENY OF VASOACTIVE INTESTINAL POLYPEPTIDE‐LIKE AND SUBSTANCE P‐LIKE IMMUNOREACTIVITY IN THE DIGESTIVE TRACT OF THE SHEEP
Authors: Harrison F. A. , Wathuta E. M.
Published: December 2014

Using the technique of indirect immunofluorescence cytochemistry, the development of structures showing vasoactive intestinal polypeptide‐like (VIP‐l.i.) and substance P‐like (SP‐l.i.) immunoreactivity was studied in the gut of the fetal sheep and of new‐born lambs. The fetuses were obtained by hysterotomy at known stages of gestation. VIP‐l.i. immunoreactivity was first detected at mid‐gestation (70 d) in neuronal structures in the myenteric plexus of the oesophagus and the forestomachs. SP‐l.i. immunoreactivity was detectable at 50 d of gestation in neuronal structures in the myenteric and submucous plexuses of the forestomachs and abomasum and in the myenteric plexus of the rectum. SP‐l.i. immunoreactivity was also seen in open‐type endocrine cells in the abomasal epithelium.

Subsequently, VIP‐l.i. staining progressively appeared caudally from the oesophagus and later cranially from the rectum. By birth the full adult staining pattern had developed in all regions except the colon. SP‐l.i. was found to progress cranially and caudally from the forestomachs and abomasum and also cranially from the rectum and by birth the gut showed staining fully representative of the adult distribution. The SP‐reactive endocrine cells appeared progressively along the intestine as the fetus developed and by birth were found predominantly in the small and large intestine with only a few in the abomasum.
EFFECTS OF REMOVING MILK FROM THE MAMMARY DUCTS AND ALVEOLI, OR OF DILUTING STORED MILK, ON THE RATE OF MILK SECRETION IN THE GOAT
Authors: Henderson A. J. , Peaker M.
Published: December 2014

Goats were milked frequently (at 10.00, 11.30, 13.00 and 14.30 h) between normal morning and afternoon milking, using a catheter to drain the milk stored in the cistern and large ducts of the mammary gland; no increase in the rate of milk secretion occurred. When the same study was repeated but oxytocin was injected to elicit milk ejection and empty the alveoli, the rate of milk secretion increased significantly. The stimulatory effect of frequent catheter‐milking plus exogenous oxytocin was evident at peak lactation as well as during declining lactation. When milk stored in the mammary gland was diluted with an isosmotic sucrose solution, the rate of milk secretion increased significantly. Again this effect was apparent at all stages of lactation. These results are discussed in relation to the local inhibitor hypothesis on the modulation of milk secretion.
A HIGH‐CONDUCTANCE CALCIUM‐DEPENDENT CHLORIDE CHANNEL IN ASCARIS SUUM MUSCLE
Authors: Thorn P. , Martin R. J.
Published: December 2014

The properties of a high‐conductance Ca‐dependent Cl channel in the body muscle membrane of the nematode parasite Ascaris suum were examined with the patch‐clamp technique. In Ascaris Ringer solution the current‐voltage relationships of the channel appeared linear during hyperpolarization with a slope conductance of 200 pS (in symmetrical 175 mM‐Cl): during depolarization the slope conductance reduced. Cation and anion replacement experiments showed this channel to be permeable to Cl ions. In artificial perienteric fluid (in symmetrical 78 mM‐Cl) the channel conductance was found to be 114 pS. Subconductance states were seen when the patch was depolarized. The channel conductance showed saturation with increasing Cl concentrations. The channel was voltage sensitive: the probability of the channel being open and the mean open time of the channel reduced when the patch was depolarized. Mean channel open times between 2·4 and 215 ms were observed. Frequency histograms of the distributions of open and closed times were fitted with two and three exponentials respectively; this suggests complex channel kinetics with multiple open and closed states. Ca applied to the intracellular surface of the patch increased in a dose‐dependent manner the number and probability of the channels being open. These channels were seen in about 20% of all patches and occasionally up to 15 channels were seen in a single patch. The distributions of the probabilities of seeing N channels open in multichannel patch records were not always well fitted by the binomial distribution: it is suggested that adjacent channels could have different probabilities of being open. The possible functions of this channel are discussed.
INPUT IMPEDANCE OF THE CANINE VERTEBRAL ARTERY
Authors: Taylor David E. , Tukmachi Emad S.
Published: December 2014

In experiments on six anaesthetized dogs it was found that the vertebral artery contributed 69·2 ± 1·7% of cerebral and 41·5 ± 2·5% of cephalic flow. The input characteristics were that the vertebral artery had a flow of 0·71 ± 0·05 ml.s−1 into an input impedance of 23·7 ± 1·9 GN.m−5.s. This compared to external and internal carotid flows of 0·69 ± 0·05 and 0·31 ± 0·02 ml.s−1 into input impedances of 23·9 ± 2·1 and 52·1 ± 2·7 GN.m−5.s respectively. Standardized per 100 g of tissue the impedances of the vertebral and internal carotid arteries were similar at 18·6 ± 2·0 and 19·1 ± 1·5 GN.m−5.s.100 g−1 respectively, while that for the external carotid was higher at 129·9 ± 10·2 GN.m−5.s.100 g−1. The impedance spectrum for the vertebral artery was of low impedance type, settling about a characteristic impedance of 2·01 ± 0·28 GN.m−5.s without significant oscillation, associated with the phase only becoming slightly positive above 10 Hz and reflexion coefficients of less than 0·25 by a frequency of 6 Hz. This was similar to the spectrum for the internal carotid artery and contrasted with the high impedance spectrum with major reflexion found for the external carotid artery.
FLOW THROUGH S‐SHAPED GLASS MODELS SIMULATING ARTERIAL TORTUOSITIES
Authors: Stehbens William E. , Stehbens Gilbert R. , Fee Conan J.
Published: December 2014

Flow patterns in twenty‐one glass models of S bends were examined using the dye‐injection technique. The glass models were of different configurations designed to simulate arterial tortuosities. In each model flow disturbances were observed in the stem distal to the S bend or in the distal portion of the S bend itself at Reynolds numbers below 2000. The disturbances were periodic in nature and mostly regular, but with considerable sensitivity to external disturbances. The sharpness of the flexures appeared to be important in determining the Reynolds number at which flow disturbances occurred. The significance of the flow disturbances is their seeming applicability to the human vascular system.
INVOLVEMENT OF THE REFLEX INCREASE IN HEART RATE IN THE DIFFERENCES IN URINARY RESPONSES TO STIMULATION OF ATRIAL RECEPTORS IN DOGS WITH DIFFERENT BLOOD VOLUMES
Authors: Hicks M. N. , Linden R. J. , Mary D. A. S. G. , Walters G. E.
Published: December 2014

The effect of increasing heart rate by increasing the rate of atrial pacing in the absence of any reflex effects from atrial receptors, by cooling the vagi to 12 °C, was studied in two groups of dogs with different blood volumes. In one group of nine dogs with a high blood volume increasing heart rate, by an amount similar to that reflexly obtained in response to stimulation of atrial receptors, resulted in significant increases in urine flow and sodium excretion; in another group of eight dogs with a low blood volume similar increases in heart rate did not result in a diuresis or natriuresis. The findings suggest that the effects of an increase in heart rate in combination with differences in blood volume could contribute to the previously reported differences in the urinary responses that result from stimulation of atrial receptors in dogs with different blood volumes.
ATTRIBUTION OF [3H]BUMETANIDE BINDING TO THE Na+K+Cl ‘CO‐TRANSPORTER’ IN RABBIT RENAL CORTICAL PLASMA MEMBRANES: A CAVEAT
Authors: Griffiths Nina M. , Simmons N. L.
Published: December 2014

The 3H‐labelled loop diuretic bumetanide has been used to investigate loop diuretic binding to purified plasma membranes from rabbit kidney cortex (and outer medulla). Bumetanide binding to partially purified cortical plasma membranes in the range 0‐10 µM, in a buffer containing principally Na, K and Cl ions, consists of a linear non‐saturable component as assessed by 100 µM unlabelled bumetanide, and a saturable component consisting of high‐ and low‐affinity binding sites, half‐maximal binding being observed at 1·3 and 220 µM, respectively. The high‐affinity site was found to be present in a fraction enriched in basolateral membrane markers when plasma membranes were further purified on a continuous Percoll gradient, whilst bumetanide binding to fractions enriched in brush‐border or mitochondrial membrane markers was of lower affinity. Several features of bumetanide binding to basolateral membrane marker‐enriched fractions are consistent with binding to the Na+K+Cl ‘co‐transporter’ inhibited by loop diuretics: half‐maximal binding was observed at 1·8 µM, with a finite maximal binding capacity of 78 pmol/mg. The relative efficacy of several loop diuretics for displacement of [3H]bumetanide was bumetanide 〉 piretanide 〉 furosemide = ethacrynic acid. Binding of loop diuretic was found to be dependent upon the medium ionic composition, Na, K and Cl being required to give maximal binding. The ability of probenecid and 4,4'‐diisothiocyanostil‐bene‐2,2'‐disulphonate (DIDS) to compete with [3H]bumetanide was tested since these compounds are known inhibitors of anion secretion in the proximal nephron. Both DIDS and probenecid were able to effectively compete with [3H]bumetanide binding. A test of the ability of these compounds to inhibit ‘co‐transport’ flux was made in intact MDCK cells using the ouabain‐insensitive 86Rb (K) influx. Probenecid, at the concentrations seen to displace [3H]bumetanide binding to renal plasma membranes, was an effective inhibitor of ‘co‐transport’ whereas DIDS was not. The adequacy of present criteria as to the identification of the ‘co‐transporter’ in renal membranes using [3H]bumetanide binding are discussed in the light of this evidence.
EFFECT ON EFFERENT CARDIAC VAGAL NERVE FIBRES OF DISTENSION OF THE URINARY BLADDER IN THE DOG
Authors: Hassan A. A. M. , Hicks M. N. , Walters G. E. , Mary D. A. S. G.
Published: December 2014

In dogs anaesthetized with chloralose, the effect of distension of the urinary bladder on the activity in efferent vagal nerves was studied; the urinary bladder was distended with warm saline, and the carotid sinuses were vascularly isolated and perfused with blood at constant flow. In one group of efferent vagal nerve fibres distension of the bladder always caused a decrease in activity. These fibres also responded to stimulation of receptors in the carotid region by an increase in activity and to stimulation of superficial branches of the left radial nerve by a decrease in activity. Another group of vagal nerve fibres which did not respond to stimulation of receptors in the carotid region, also did not respond to distension of the urinary bladder. It is concluded that distension of the urinary bladder results in the response of a decrease in activity in efferent cardiac vagal nerve fibres, onto which converge the effects of stimulating receptors in the carotid region and the somatic nerves.
SINGLE‐CHANNEL CURRENTS FROM ZONA‐FREE MOUSE EGGS
Authors: Bountra C. , Martin R. J.
Published: December 2014

Cell‐attached patch recordings were made from zona‐free mouse eggs to examine currents at the single‐channel level; two types were identified. A channel with a mean conductance of 130 pS showed changes in reversal potential on dilution of the patch pipette solution consistent with a cation channel; the channel current persisted when the only cation in the pipette was K+: it was concluded that this channel was permeable to K+. The binomial distribution was used to describe the proportion of time 0, 1, 2, ..., n channels were open in multichannel recordings of the K+ channel. Bursts of inward currents of about 1 pA, which showed voltage activation and could be recorded in the presence of CsCl and tetraethylammonium (TEA), were identified as Ca2+ channels.
THE EFFECT OF ACUTE JOINT DISTENSION ON MECHANORECEPTOR DISCHARGE IN THE KNEE OF THE CAT
Authors: Ferrell W. R.
Published: December 2014

Recordings were obtained from afferents travelling in the posterior articular nerve of the cat knee joint. These arose from tonically active slowly adapting mechanoreceptors which were located in the joint capsule and whose conduction velocities were in the group II range. Intra‐articular fluid injection resulted in enhancement of receptor discharge. Both the static index (adapted discharge 2s after ramp displacement) and the dynamic index (difference between peak discharge during joint displacement and that occurring 0·5s later) increased after injection. However, whereas the dynamic index increased by three‐ to fivefold the static index never exceeded a twofold increase. Incremental rise of intra‐articular volume resulted in progressive increase in both parameters at all angular velocities. Thus both position and velocity sensitivity are enhanced by the acute introduction of fluid into the synovial cavity.
TRANSPORT OF SELENATE AND SULPHATE ACROSS THE INTESTINAL BRUSH‐BORDER MEMBRANE OF PIG JEJUNUM BY TWO COMMON MECHANISMS
Authors: Wolffram S. , Grenacher B. , Scharrer E.
Published: December 2014

The objectives of the present study were to find out whether selenate and sulphate are transported by a common Na+‐dependent transport mechanism across the intestinal brush‐border membrane and whether selenate is also transported by the anion‐exchange system transporting sulphate across the brush‐border membrane. Results from cis‐inhibition as well as from trans‐stimulation experiments show that selenate and sulphate are transported across the brush‐border membrane by both Na+ co‐transport and anion exchange. The influence of various dicarboxylates (oxalate, oxaloacetate, glutamate) and of the anion‐exchange inhibitor 4,4'‐diisothiocyanostilbene‐2,2'‐disulphonate (DIDS) on selenate and sulphate transport across the brush‐border membrane was also investigated. Under Na+‐gradient conditions selenate uptake across the brush‐border membrane was reduced by oxalate and oxaloacetate but not by L‐glutamate or L‐leucine. Additionally sulphate uptake under this condition was significantly inhibited by oxalate (about 50%) and DIDS (25%). Sulphate transport by anion exchange was inhibited about 80% by both oxalate and DIDS. These results suggest that under Na+‐gradient conditions sulphate (selenate) uptake in part occurs via anion exchange. Furthermore, oxalate seems to inhibit both Na+‐sulphate (selenate) co‐transport and sulphate (selenate) transport by anion exchange.
COMPARISON OF FORCE‐VELOCITY CHARACTERISTICS OBTAINED USING TWITCHES AND TETANI FROM IN SITU RAT SKELETAL MUSCLES
Authors: de Haan A.
Published: December 2014

Force‐velocity and power‐velocity characteristics of three different rat skeletal muscle‐tendon complexes (soleus, extensor digitorum longus and medial gastrocnemius) were obtained using twitch and tetanic contractions. No differences were found between twitches and tetani with respect to the shape of the force‐velocity curves, or to the velocity at which the highest power output occurs. The results indicate that twitch contractions can be used to standardize muscle preparations in experiments aimed to study muscle energetics during dynamic contractions.
RELATION BETWEEN TRANS‐SYNOVIAL FLOW AND PLASMA OSMOTIC PRESSURE, WITH AN ESTIMATION OF THE ALBUMIN REFLECTION COEFFICIENT IN THE RABBIT KNEE
Authors: Knight A. D. , Levick J. R. , McDonald J. N.
Published: December 2014

The volume of synovial fluid in a joint correlates inversely with plasma colloid osmotic pressure (COP). The inferred influence of plasma osmotic forces on trans‐synovial flow was investigated directly here, in isolated perfused hindquarters of sixteen rabbits. Flow of intra‐articularly infused Krebs solution across the synovial lining of the cannulated knee was recorded at controlled intra‐articular pressure (18 cmH2O). Colloid osmotic pressure in the synovial microcirculation was varied by perfusion with oxygenated red cells resuspended in albumin solution or plasma from an extra‐corporeal system at constant perfusion pressure. Studies in vitro showed that the COP versus concentration curve for commercial bovine albumin samples was variable and not reliably described by a widely used polynomial. The rate of trans‐synovial absorption Qs was a positive linear function of intravascular COP πn (r = 0·936, P 〈 0·001, n = 83). The average slope dQs/dπp was 0·20 µl min−1 cmH2O−1 (S.E. ± 0·01 µl min−1 cmH2O−1), the slope depending on hydraulic conductance and osmotic reflection coefficient. Trans‐synovial flow was a negative linear function of synovial capillary pressure (Pc). Absolute slope dQs/dπp was on average only 78% of dQs/dPc in the same joint. The osmotic reflection coefficient of the blood‐joint barrier to serum albumin was estimated from these slopes as 0·78‐0·81 (S.E.M. ± 0·06). Vascular perfusion with a hyperosmolar solution of glucose, sucrose or NaCl generated a transient, rapidly decaying osmotic absorption from the joint cavity, with a half‐life of 17‐60 s. A reversed osmotic transient occurred on reperfusion with isotonic fluid. It was concluded that the blood‐joint barrier, which comprises fenestrated endothelium and synovial intima, approximates to an imperfect semipermeable membrane for albumin solutions, justifying the application of Starling's hypothesis to trans‐synovial flow. For small solutes the tissues form a highly permeable but nevertheless slightly osmotically reflective membrane.
THE EFFECT OF ACUTE JOINT INFLAMMATION ON FLEXION REFLEX EXCITABILITY IN THE DECEREBRATE, LOW‐SPINAL CAT
Authors: Ferrell W. R. , Wood L. , Baxendale R. H.
Published: December 2014

Experiments were performed to investigate whether acute knee joint inflammation, induced by intra‐articular injection of carrageenan and kaolin, significantly influences the magnitude of the flexion withdrawal reflex of knee flexors in the decrebrate, low‐spinal cat. It was observed that after injection of these inflammatory agents, reflex intensity increased with a time course that matched the development of the inflammatory process, as assessed by monitoring the intra‐articular temperature. Control experiments involving intra‐articular injection of saline showed neither a rise in intra‐articular temperature, nor any change in reflex intensity. The normal pattern of modulation of reflex intensity with changing joint angle was abolished in the inflamed joint with the reflex being equally intense at all positions tested. Abolition of neural activity in the inflamed joint by intra‐articular injection of lignocaine resulted in a marked decrease in the reflex back to control values, suggesting that there is no maintained increase in central excitability in the absence of joint afferent input. It was also observed that the spontaneous activity of knee flexor motor units was modulated during continuous passive rotation of the knee, with activity being greater in extension than in flexion. This pattern reversed when the knee was acutely inflamed, but could be returned to the control pattern by joint anaesthesia, although now the response was attenuated when compared to the control.
THYROID HORMONE NUCLEAR RECEPTORS IN SKELETAL MUSCLE AS INFLUENCED BY ENVIRONMENTAL TEMPERATURE AND ENERGY INTAKE
Authors: Dauncey M. J. , Ingram D. L. , Brown D. , Hayashi M.
Published: December 2014

Young litter‐mate pigs were kept at either 10 or 35 °C and fed either a high (H) or a low (L) food intake producing four groups: 10 H, 10 L, 35 H and 35 L. The numbers of receptors for thyroid hormone in the nuclei of skeletal muscle were estimated and found to be greatest in the 35 H group and least in the 10 L group. The numbers of receptors in the 10 H and 35 L groups were similar and took intermediate values. It is suggested that the differences in receptor numbers represent an adaptation which regulates the tissue response to thyroid hormone. Some possible consequences of this adaptation are discussed.
PRESSURES IN NORMAL AND ACUTELY DISTENDED HUMAN KNEE JOINTS AND EFFECTS ON QUADRICEPS MAXIMAL VOLUNTARY CONTRACTIONS
Authors: Wood L. , Ferrell W. R. , Baxendale R. H.
Published: December 2014

Pressures were recorded in ten knees from five subjects with informed consent. Resting intra‐articular pressures were found to be sub‐atmospheric with a mean value of ‐5±1·5 mmHg (S.E. of mean). There was little variation in intra‐articular pressure with changing joint angle in the normal joint. Infusion of as small a volume as 5 ml of sterile saline into the joint cavity caused the intra‐articular pressure to increase to supra‐atmospheric levels. Changing joint angle now produced clear modulations in intra‐articular pressure. Pressure increased as the limb was moved out to extension and back to flexion with a minimum occurring in the mid‐range. These modulations were more pronounced with active positioning of the joint than with passive positioning. Successive increases in intra‐articular volume produced increases in intra‐articular pressure as well as the degree of modulation of intra‐articular pressure with joint angle. Cyclical flexion‐extension movements caused a progressive decrease in the maximum pressure observed in extension. Non‐noxious distension of the knee joint caused substantial reductions in the magnitude of isometric and isokinetic maximal voluntary contractions of quadriceps due to a reflex inhibition from joint mechanoreceptor afferents.
POSTURAL THIXOTROPY AT THE HUMAN HIP
Authors: Walsh E. G. , Wright G. W.
Published: December 2014

In these experiments the person relaxed on his back with one leg free to swing in the horizontal plane into abduction or adduction; the weight was taken by a cord attached to the ceiling over the hip joint. Records of acceleration following a displacement showed a series of decrementing swings which could last for more than 10 s. The imposition of sinusoidal torques generated by a printed motor showed that the system was non‐linear for when small torques were used the resonant frequency rose indicating stiffening. The use of a biasing force to move the mean position of the leg showed that the stiffening was not related to any particular position and was the result of the low level of movement. Under certain conditions the stiffening could be abolished by larger active or passive movements. Even a single active or passive movement could be effective. Such a history‐dependent compliance was an indication of postural thixotropy. It was present and apparently normal in patients with artificial joints. Reasons are given for believing that the effects are a reflection of muscle properties.
EFFECT OF LIDOCAINE ON ACTION POTENTIALS, CURRENTS AND CONTRACTIONS IN THE ABSENCE AND PRESENCE OF OUABAIN IN GUINEA‐PIG VENTRICULAR CELLS
Authors: Mitchell M. R. , Plant S.
Published: December 2014

The effects of lidocaine have been investigated on electrical and contractile activity in guinea‐pig ventricular cells in the absence and in the presence of ouabain. At low (therapeutic) doses, lidocaine induced a small reduction in action potential duration and contraction but had no effect on transient depolarizations or, under voltage‐clamp conditions, on the transient inward currents. At much higher concentrations of lidocaine (〉 500 µM), where the fast inward sodium current was substantially blocked, there was also a marked reduction in the amplitude of the calcium current and accompanying phasic contraction. Again, lidocaine did not inhibit the transient depolarizations or transient inward currents. This suggests that there is no direct effect of lidocaine on the calcium‐induced release of calcium from the sarcoplasmic reticulum and that lidocaine does not indirectly inhibit arrhythmic activity by reducing intracellular sodium in the isolated ventricular cell. Possible mechanisms for the antiarrhythmic action of lidocaine in whole heart are discussed.
SODIUM ENTRY INTO HUMAN PLACENTAL MICROVILLOUS (MATERNAL) PLASMA MEMBRANE VESICLES
Authors: Chipperfield A. R. , Steele Lorna W. , Langridge‐Smith Jane E.
Published: December 2014

The uptake of sodium into vesicles isolated from the microvillous, maternal‐facing plasma membrane of human placenta was studied. In equilibrium exchange conditions, sodium entry increased with time towards an equilibrium value after 30‐60 min. Over 90% of the uptake was into an osmotically active space and the initial rate of uptake was halved by amiloride but unaffected by loop diuretics and capnophorin inhibitors. The apparent inhibition constant (Ki) for amiloride was 3·5 x 10−6 M and the Michaelis constant (Km) with respect to sodium of the amiloride‐sensitive component was 7‐11 mM. With an imposed outward H+ gradient, sodium was transiently accumulated within the vesicles. The overshoot was abolished by amiloride and shown, by experiments with FCCP (carbonyl cyanide p‐trifluoromethoxy‐phenylhydrazone) and potassium and valonomycin, not to be dependent on any electrical potential generated by the H+ gradient. The evidence for Na+‐H+ exchange at this surface and its possible functions are discussed.
THE BRAIN STEM LOCALIZATION OF VAGAL PREGANGLIONIC NEURONES IN THE FERRET, MUSTELA PUTORIUS FURO
Authors: Withington-Wray D. J. , Spyer K. M.
Published: December 2014

Horseradish peroxidase‐wheatgerm agglutinin was injected into the cervical vagus nerve of adult ferrets. Efferent fibres coursing in the vagus nerve were shown to originate in the dorsal vagal motor nucleus (DmnX), the nucleus ambiguus (nA), a region ventral to the nucleus ambiguus (VnA) and the reticular formation between DmnX and nA. The distribution of vagal preganglionic neurones in the ferret is compared with data already obtained in similar studies conducted in other mammals.
IN VITRO MOTILITY OF NON‐PREGNANT RAT UTERINE HORNS
Authors: Mancinelli R. , Racanicchi C. , Guariglia L. , Bertuzzi A. , Vitelli R. , Salinari S.
Published: December 2014

The in vitro spontaneous mechanical and electrical activity of the non‐pregnant rat uterine horn was investigated. An isometric isovolumic preparation was used to obtain records of intraluminal pressure, axial force, extracellular electrical activity and horn morphology. Mean intraluminal pressure was 28·6 cmH2O and mean force 2·5 g. Burst electrical activity was initiated at the ovarian end in 70% of the cases. Detailed analysis of electrical and mechanical events during a single contraction showed a preparatory phase involving the longitudinal muscle layer, followed by a stronger contractile event involving both longitudinal and circular layers. Moreover, the mechanical activity was modulated at the frequency of a component (0·16‐0·20 Hz) of the slow electrical activity of the horn. Burst electrical activity appeared at five equidistant electrodes along the horn with variable delays: the highest delays (mean values 7·4 s for burst activity initiated at the ovarian end and 6·5 s at the vaginal end) were observed in the middle part of the horn. The spontaneous contraction of the segment appeared to be due to the activation of separate regions of the horn (i.e. an ovarian and a cervical region), more than to a propagated excitatory action.
THE EFFECTS OF PHYSOSTIGMINE SULPHATE EYEDROPS ON HUMAN VISUAL FUNCTION
Authors: Kay C. D. , Morrison J. D.
Published: December 2014

Instillation of 0·25% physostigmine sulphate eyedrops in twelve subjects caused a sustained miosis, a transient reduction in near‐point and a transient increase in the amplitude of accommodation. The latter had a peak at 30 min and had recovered by 90 min, though its amplitude varied widely between subjects. Contrast sensitivity to stationary grating patterns of 3‐30 cycles/deg and phase‐reversed grating patterns of 0·5‐3 cycles/deg was reduced transiently with a time course similar to that of the increase in accommodation. The peak reduction in contrast sensitivity was correlated significantly with the peak amplitude of accommodation. Contrast sensitivity to laser interference fringes, observed in Maxwellian view where the effects of defocus are bypassed, was also reduced, indicating that physostigmine also had a direct deleterious action on the visual system.
AN EVALUATION OF THE EFFECTIVENESS OF INTRAMUSCULAR ATROPINE OR HOMATROPINE EYEDROPS IN PREVENTING THE EFFECTS OF PHYSOSTIGMINE EYEDROPS ON HUMAN VISION
Authors: Kay C. D. , Morrison J. D.
Published: December 2014

An intramuscular injection of 2 mg atropine sulphate was given at either 8 or 120 min prior to instillation of 0·25% physostigmine sulphate eyedrops. In this way, the maximum accommodative change and the concomitant reduction in contrast sensitivity caused by physostigmine coincided with, respectively, the peak plasma atropine concentration or the fully developed mydriasis and reduction of near‐point accommodation caused by atropine. Atropine at both times did not affect the miosis, the reduction in near‐point, the increase in accommodation or the reduction in contrast sensitivity caused by physostigmine. Contrast sensitivity to a phase‐reversed grating pattern was actually diminished by atropine, though this was not statistically significant. By contrast, 2% homatropine hydrobromide eyedrops did effectively anatagonize physostigmine's actions. This indicates that the rate of delivery of atropine from the intramuscular injection was insufficient to compete against the ocular effects of physostigmine.