bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic stimulation accelerates functional recovery of immobilized soleus muscles of the rabbit
Authors: Cotter MA , Cameron NE , Barry JA , Pattullo MC
Published: December 2014

Unilateral immobilization of rabbit hindlimbs was carried out for 2 weeks with an ankle angle of 90 deg. This was followed either by natural recovery for a further 2 or 4 weeks, or by chronic electrical stimulation of the soleus nerve during 2 weeks recovery using a low‐frequency pattern of activation. Immobilization caused gross degeneration and functional disruption of soleus. Mean fibre area was reduced by 60% compared with unoperated controls, twitch and tetanic tensions by 90% and there was speeding of the rising phase of contraction. Natural recovery for 2 weeks had little effect; some regeneration occurred but muscle fibres remained atrophied and immature as indicated by the histochemical expression of both fast and slow myosin. Function continued to be grossly impaired, twitch and tetanic tensions were 66 and 79% reduced and the time‐to‐peak twitch tension 31% faster than controls. Prolonging the natural recovery period to 4 weeks increased muscle fibre area to 60% of normal, and increased the acquisition of mature staining properties but most functional characteristics remained impaired. Stimulated muscles had normal fibre areas, mature appearance and functional improvements which matched and in most cases exceeded those seen after natural recovery for 4 weeks. Thus chronic low‐frequency stimulation of soleus muscles accelerates recovery of structure and function following degenerative immobilization atrophy and may represent an important therapeutic aid in patient rehabilitation.
MDL 72222 (a selective 5‐HT3 receptor antagonist) prevents stimulation of intrapulmonary C fibres by pulmonary embolization in anaesthetized rabbits
Authors: Kay IS , Armstrong DJ
Published: December 2014

We have investigated the effects of the intravenous administration of 5‐hydroxytryptamine upon the discharge frequency of pulmonary stretch receptors, irritant receptors and C fibres. Only C fibres were stimulated by this autacoid. MDL 72222 a selective 5‐HT3 receptor antagonist blocks the C fibre stimulation by 5‐hydroxytryptamine. It also blocks the C fibre response to miliary pulmonary embolism. These data confirm the hypothesis that 5‐hydroxytryptamine is the humoral link between pulmonary embolism and tachypnoea.
Cardiovascular effects of parathyroid hormone in conscious sheep
Authors: Jordan LR , Dallemagne CR , Cross RB
Published: December 2014

The cardiovascular effects of the synthetic amino terminal fragment of parathyroid hormone, PTH(1‐34), were studied in intact conscious sheep. Physiological doses of bovine (b) PTH(1‐34), 0.188, 0.376, 0.56 and 0.75 micrograms kg‐1 h‐1 were infused in random order into conscious sheep for periods of 1 h each. Isotonic saline was infused as a control. Mean arterial blood pressure (MABP) decreased from 99.2 +/‐ 1.2 mmHg during the control infusion to 88.9 +/‐ 1.4 mmHg during infusion of the highest dose of PTH. Heart rate (HR) increased from 81.6 +/‐ 7.3 beats min‐1 during the control infusion to 142.3 +/‐ 14.0 beats min‐1 at the highest PTH dose and plasma renin activity (PRA) increased from 0.33 +/‐ 0.15 ng ml‐1 h‐1 to 1.54 +/‐ 0.46 ng ml‐1 h‐1. Cardiac output (CO), calculated by an indirect method, increased to 176 +/‐ 28% of the control values. The changes in all four parameters were dose dependent. Renal blood flow (RBF) increased during the PTH infusion period.
Resonant frequency at the wrist in hypermobile women
Authors: Walsh EG , Lambert M , Wright GW , Powers N , Nuki G
Published: December 2014

The resonant frequency of the wrist has been measured in sixteen hypermobile and nine normal women at ten levels of peak torque. At the lowest level the results were identical but at the others the hypermobile values were lower. Damping and thixotropy appeared to be normal. In another group the grip strength of hypermobile subjects was similar to that of controls. The possibility that the connective tissue of the musculature of hypermobile subjects is of enhanced compliance is discussed.
Compensatory increase in lactase expression by enterocytes of neonatal pigs on a low energy intake
Authors: Tivey DR , Hilton KJ , Dauncey MJ
Published: December 2014

A restricted energy intake in the immediate postnatal period has been found to result in a significant increase in the maximal expression of lactase by enterocytes from 2‐week‐old pigs. Although villus size was significantly reduced on a low compared with a high food intake, total villus lactase activity was unaffected because of the compensatory increase in lactase expression by individual enterocytes.
Cumulative dose‐response curves for bethanechol‐induced electrogenic secretion in rat jejunum in vitro: is tachyphylaxis a significant factor?
Authors: Przyborski SA , Levin RJ , Young A
Published: December 2014

Electrogenic secretion was monitored as the short‐circuit current (Isc) by an automatic voltage clamp across the isolated rat jejunum incubated in vitro. Responses to consecutive additions of bethanechol (1 mM) to the serosal surface showed tachyphylaxis. Addition of prostaglandin E2, however, after a single dose of 1 mM‐bethanechol, induced an undiminished Isc response indicating that the tachyphylaxis was homologous. Dose‐response curves for serosal applications of bethanechol obtained by serial‐cumulative addition did not show tachyphylaxis when compared with those from a non‐cumulative technique. The method of automatically recording the intestinal Isc with serial‐cumulative addition of a serosal secretagogue gives dose‐response curves free from tachyphylaxis.
Parathyroid hormone‐(1–34) peptide activates cyclic adenosine 3',5'‐monophosphate in the human placenta
Authors: Williams JM , Abramovich DR , Dacke CG , Mayhew TM , Page KR
Published: December 2014

Dually perfused human term placental lobules were exposed to forskolin, bovine parathyroid hormone (bPTH(1‐34)) and human parathyroid hormone related‐peptides, hPTHrP(1‐34), hPTHrP(67‐86)NH2 or PTHrP(107‐138) for 15 min in the presence of 3‐iso‐butyl‐1‐methyl‐xanthine (IBMX); control lobules were exposed to IBMX alone. Homogenates of these tissues were then assayed for cyclic adenosine 3',5'‐monophosphate (cyclic AMP) and results normalized per mg of protein. Exposure to forskolin or bPTH(1‐34) on both sides, and exposure to bPTH(1‐34) at a concentration of 30 nM on the maternal side of the placenta or 120 nM on the fetal side of the placenta, significantly enhanced tissue cyclic AMP production compared with tissue exposed to IBMX alone. Exposure to hPTHrP(1‐34), hPTHrP(67‐86)NH2 and hPTHrP(107‐138) at a concentration of 30 nM on both sides of the placenta had no significant effect upon tissue cyclic AMP production.
Action of sympathomimetic drugs on the bronchial circulation of the horse
Authors: Sanders EA , Gleed RD , Hackett RP , Dobson A
Published: December 2014

In the quietly standing horse I.V. administration of adrenaline decreased, and of dobutamine increased, bronchial artery flow. These changes paralleled changes in arterial pressure. With phenylephrine and noradrenaline bronchial artery flow decreased while arterial pressure increased, indicating active vasoconstriction in the bronchial circulation. With clenbuterol an increase in bronchial artery flow was accompanied by a decrease in systemic blood pressure, indicating bronchial arterial vasodilatation. We conclude that alpha‐constrictor and beta 2‐dilator receptors are present in the bronchial artery bed and that stimulation of these receptors could explain changes in flow seen in the horse during exercise and anaesthesia.
The effects of cholesterol depletion on the sodium pump in human red cells
Authors: Lucio FJ , Hendry BM , Ellory JC
Published: December 2014

Sodium pump function has been studied in human erythrocytes depleted of membrane cholesterol by incubation with phosphatidylcholine liposomes. The cells were sodium loaded by incubation in alkaline sodium phosphate and sodium pump activity was assessed by measurements of ouabain‐sensitive 86Rb uptake at 37 degrees C. Cholesterol depletion had a biphasic effect; depletion by 5–25% increased sodium pump activity by a mean of 16.1% (S.D. 3.2%), whereas depletion by 35–50% decreased sodium pump activity by a mean of 14.8% (S.D. 3.8%). Cholesterol depletion had no reproducible effect on the ouabain‐insensitive uptake of Rb. These results support the hypothesis that there may be an optimum membrane cholesterol content for sodium pump function.
Arginine vasopressin stimulation of chloride secretion in Madin‐Darby canine renal epithelial layers
Authors: Simmons NL , Brown CD
Published: December 2014

Arginine vasopressin (AVP) at a concentration of 0.1 microM stimulates an inward short‐circuit current (SCC) in voltage‐clamped Madin‐Darby canine kidney epithelial layers with a mean peak of 3.1 +/‐ 0.8 microA cm‐2 (n = 6). The response to AVP is markedly attenuated when inward SCC is stimulated with forskolin or prostaglandin E1, in Cl(‐)‐free media and by the Cl(‐)‐transport inhibitors, bumetanide and 5‐nitro‐2‐(3‐phenylpropylamino)‐benzoic acid, consistent with an AVP‐stimulated basal to apical Cl‐ secretion. Endogenous release of prostaglandins may contribute to AVP stimulation of Cl‐ secretion.
Central and peripheral doses of cholecystokinin that inhibit feeding in pigs also stimulate vasopressin and cortisol release
Authors: Parrott RF , Ebenezer IS , Baldwin BA , Forsling ML
Published: December 2014

The effects on vasopressin and cortisol secretion of centrally and peripherally administered cholecystokinin octapeptide (CCK) were investigated in conscious prepubertal pigs. Injection of 1.3 micrograms CCK into the lateral cerebral ventricle resulted in a sustained increase in plasma vasopressin after a latency of 5 min but no change in cortisol concentrations. Intravenous injection of 0.7 and 1.3 micrograms/kg CCK initiated a rapid surge (within 2 min) in plasma vasopressin and a later increase in cortisol secretion. The time course of the vasopressin response to the central injection of CCK was found to be similar to the period of behavioural inhibition induced when an equivalent dose of the peptide was given by the same route in an earlier feeding experiment. An analogous situation was also observed when CCK was given peripherally and, in this case, the threshold dose at which the behavioural and endocrine responses were induced was found to be the same.
Intracellular degradation of newly synthesized casein in perfused rat mammary gland
Authors: Wilde CJ , Kerr MA , Calvert DT
Published: December 2014

Degradation of newly synthesized casein in rat mammary gland perfused in situ was measured by a pulse‐chase method using [3H]proline. Casein degradation during secretion was observed in the absence of prolactin, but not with prolactin present. Partial inhibition by chloroquine showed that hormone‐dependent degradation occurred intracellularly by a lysosomal mechanism. The study indicates that this post‐translational mechanism is a physiological regulator of net casein secretion.
Rabbit intestinal smooth muscle calcium current in solutions with physiological calcium concentration
Authors: Aaronson PI , Russell SN
Published: December 2014

The calcium channel current in enzymatically isolated cells of the longitudinal muscle of rabbit jejunum was studied using the whole‐cell voltage clamp technique. The current‐voltage relationship was measured in cells held at potentials ranging from ‐90 to ‐30 mV in the presence of 1.5 mM‐calcium or barium in order to test for the presence of multiple current components. The kinetics and current‐voltage relationship of the current showed no evidence of a discrete low‐threshold or ‘transient’ current. Measurable current was observed at ‐55 mV. Current availability was dependent on the holding potential but not on the test potential, suggesting the presence of only one type of calcium channel. A component of current persisted for at least 25 s following depolarization. Nifedipine reduced the Ca2+ current amplitude without shifting the current‐voltage relationship; the degree of inhibition was enhanced by depolarization of the holding potential. The peak and sustained currents were similarly inhibited by nifedipine. The results indicate the presence of a single type of dihydropyridine‐sensitive calcium channel current which is partially activated at or near the physiological resting membrane potential of these cells.
The influence of temperature on the effects of acetylcholine and adrenaline on the membrane potential and 86Rb efflux in mouse pancreatic B‐cells
Authors: Debuyser A , Drews G , Henquin JC
Published: December 2014

Pancreatic mouse islets were used to evaluate the influence of temperature on the B‐cell response to acetylcholine and adrenaline. At 20 degrees C, the rate of 86Rb efflux from islet cells was lower, the membrane potential of B‐cells was slightly less negative, and glucose‐induced electrical activity was characterized by longer slow waves than at 37 degrees C. At 20 degrees C, the acceleration of 86Rb efflux produced by 1 microM‐ACh was only reduced by 25%, but its reversibility was slower. Acetylcholine rapidly depolarized the B‐cell membrane and increased electrical activity regardless of the temperature. However, this increase was characterized by the appearance of short slow waves of high frequency at 37 degrees C and by continuous spiking at 20 degrees C. Adrenaline (1 microM) inhibited 86Rb efflux at 37 and 20 degrees C, but the amplitude of the inhibition was decreased and its time course and reversibility were altered at the lower temperature. Adrenaline repolarized the B‐cell membrane and abolished glucose‐induced electrical activity for a longer period at 20 degrees C than at 37 degrees C. In conclusion, no marked decrease in signal transduction occurs at 20 degrees C. This suggests that the difficulty of identifying the currents induced by acetylcholine and adrenaline in patch‐clamp experiments performed at room temperature is probably due to the small magnitude of these currents.
Influence of ileal resection, type of diet and ursodeoxycholic acid on biliary secretion in rats
Authors: Lisbona F , Campos MS , Coves F , Garcia JA , Barrionuevo M , Lopez-Aliaga I
Published: December 2014

We studied the effects of the type of dietary fat and of ursodeoxycholic acid, an exogenous bile acid added to the diet, on bile physiology in rats with 50% resection of the distal small intestine. The amount of fat was the same (4%) in all diets assayed, which differed only in the type of fat, (olive oil in diet A, and 1/3 medium‐chain triglycerides, 1/3 sunflower oil and 1/3 olive oil in diet B). The removal of 50% of the distal small intestine raised the de novo hepatic synthesis of bile acids with respect to controls, regardless of whether diet A or diet B was given. The addition to diet B of ursodeoxycholic acid decreased bile flow and osmotic activity of bile acid in resected rats and raised bile acid‐independent bile flow in comparison to resected rats given diet B without ursodeoxycholic acid.
Additional force during stretch of single frog muscle fibres following tetanus
Authors: Kilgore JB , Mobley BA
Published: December 2014

Single fibres from the anterior tibialis muscles of frogs were used in paired difference experiments to investigate the long‐term effect (up to 3.8 s) of tetanic stimulation on fibre stiffness during relaxation. The fibres were stretched from sarcomere lengths of 2.5 microns to 3.0 microns at constant velocities for periods ranging from 0.5 to 1.75 s. The first stretch of each pair took place when the fibres had not experienced a tetanus for at least 5 min. The second stretch took place 20–30 s after the first, but it was preceded by a tetanus (100 Hz stimulation applied for 190 ms; temperature, 23 degrees C). The force produced by the first stretch was subtracted from the force produced by the second to produce a paired difference. The fibres were held at the sarcomere length of 3.0 microns except for a brief period of time immediately prior to the stretches (1200 or 1450 ms). During those periods the fibres were shortened to 2.5 microns (250 ms) and then held at 2.5 microns, regardless of whether a tetanus was elicited, for either 950 or 1200 ms. The second stretch of each pair began either at the end of, or 250 ms after, the last stimulating pulse of the tetanus. At every velocity of stretch, the force produced by the fibres during the stretches was greater when the stretches were preceded by a tetanus than when they were not, and the additional force peaked at the conclusion of the stretches. The additional force, which was produced during the stretches following the tetani, declined for the remainder of the data acquisition period (up to 3 s) following the completion of stretches; it extrapolated to zero at 7–8 s after the completion of the stretches. The magnitude of the additional force was a non‐linear direct function of the rate of stretch. Thixotropy or an increased stiffness to stretch was observed in all of the fibres following periods of quiescence.
Resistance to fatigue of single muscle fibres from Xenopus related to succinate dehydrogenase and myofibrillar ATPase activities
Authors: van der Laarse WJ , Lannergren J , Diegenbach PC
Published: December 2014

This report describes how the resistance to fatigue of a muscle fibre relates to the fibre's most important ATP‐producing and ATP‐consuming reactions. Twelve intact single muscle fibres were dissected from lumbrical muscles of Xenopus laevis. Their resistance to fatigue induced by repeated tetanic stimulation was determined, as well as their succinate dehydrogenase activity and calcium‐stimulated myofibrillar ATPase activity. The enzyme activities were determined by means of quantitative histochemistry. It was found that resistance to fatigue correlates with succinate dehydrogenase activity (r = 0.83) and with myofibrillar ATPase activity (r = ‐0.74). The highest correlation was found between resistance to fatigue and the ratio of succinate dehydrogenase to myofibrillar ATPase activity (r = 0.93). It is concluded that muscular fatigue is closely related to cellular energetics.
The mechanical effects of rhinoceros horned viper (Bitis nasicornis) venom on the isolated perfused guinea‐pig heart
Authors: Alloatti G , Gattullo D , Losano G , Marsh NA , Pagliaro P , Vono P
Published: December 2014

In the guinea‐pig Langendorff heart preparation, addition of 0.1 mg Bitis nasicornis venom to the perfusion solution caused transient increases in heart rate (HR) and left ventricular systolic pressure (LVSP) with peak increases at 2 min. With higher doses (0.6 and 1.4 mg), these increases were followed by the return of HR to normal, significant decreases in LVSP below control values and marked increases in left ventricular diastolic pressure. Histaminergic blockade with ranitidine reduced the positive responses. The results suggest that a venom component, possibly acting on intracellular calcium movement, could be responsible for both positive and negative effects.
Agonist‐induced fluctuations in cytoplasmic calcium in primary cultures of bovine endothelial cells
Authors: Gillespie JI , Greenwell  , Johnson C
Published: December 2014

Endothelial cells play an important role in the vascular responsiveness to many stimuli by releasing locally active agents. The intracellular signal which links the external stimulus to the release of the active compounds is almost certainly an elevation in cytoplasmic calcium (Cai2+). Thus a detailed knowledge of Cai2+ regulation is central to an understanding of the physiology and pharmacology of endothelial cells. The present experiments, on single bovine aortic endothelial cells, demonstrate that agonists stimulate complex changes in Cai2+. These include rapid and regular fluctuations in Cai2+ which are different from the oscillations reported in other endothelial cells and non‐excitable cells. The fluctuations are completely abolished in media containing low calcium, 2 mM‐cobalt or caffeine but are not affected if the cells are bathed in isotonic potassium solutions. The hypothesis is put forward that the fluctuations in Cai2+ are associated with localized influxes of calcium and are possibly involved with the recycling of calcium between the internal stores, the cytoplasm and the external medium.
Outward currents in rabbit pulmonary artery cells dissociated with a new technique
Authors: Clapp LH , Gurney AM
Published: December 2014

Single cells from the rabbit pulmonary artery were isolated using a new and convenient procedure. Strips of muscle were incubated overnight in papain at 6 degrees C and dispersed the following morning after warming the tissue for 10 min. This method consistently produced a high yield of relaxed cells, which reversibly responded to vasoconstrictors and remained viable for many hours. The electrophysiological properties of these cells were studied using the patch‐clamp technique in the whole‐cell configuration. In physiological Ca2+ solution with K(+)‐filled pipettes, cells had a high input resistance (approximately 17 G omega) and an average resting potential of ‐55 mV. In voltage clamp, several components of outward current could be identified. Depolarizing voltage steps revealed a prominent, transient current (Itran), having extremely rapid activation (less than 5 ms) and inactivation (less than 15 ms) kinetics. Itran was followed by a more slowly activating current (IKso) that was sustained over 100 ms. Both currents were essentially abolished by a 4‐aminopyridine (4‐AP) and sensitive to Ca2+ influx. IKso, but not Itran, was blocked by tetraethylammonium (TEA) and had the properties of a Ca(2+)‐activated K+ current. Holding the membrane potential at ‐40 mV completely inactivated Itran and unmasked a time‐independent, background current superimposed on IKso. The background current was also blocked by 4‐AP. In addition, when adenosine triphosphate (ATP), but not guanosine triphosphate (GTP), was omitted from the patch‐pipette, spontaneous bursts of outward current (SOCs) were superimposed on the voltage‐activated currents. However, since SOCs were rarely observed when ATP and GTP were present together, they are unlikely to be active under physiological conditions. Thus at least four types of outward current can be distinguished in isolated rabbit pulmonary artery cells. These include a novel transient current which could be activated from the resting potential. It activates much more rapidly than outward currents previously reported in vascular muscle, and would rapidly oppose action potential firing. This current could therefore be responsible for the inability of large elastic arteries to fire action potentials.
Avian lower intestine adapts to dietary salt (NaCl) depletion by increasing transepithelial sodium transport and microvillous membrane surface area
Authors: Sodring Elbrond V , Dantzer V , Mayhew TM , Skadhauge E
Published: December 2014

A tissue sampling scheme for tandem assessments of whole‐organ physiology and ultrastructure was applied to the lower intestine (coprodaeum) of White Plymouth Rock hens on low‐ and high‐NaCl diets. The objective was to correlate net amiloride‐sensitive Na transport determined using the Ussing chamber with the plasma membrane surface areas due to microvilli at the epithelial cell apex. Hens kept on the low‐NaCl diet for 3‐4 weeks displayed a substantial increase in short‐circuit current and in total microvillous membrane surface area. The latter rose from a group mean +/‐ S.E.M. of about 90 +/‐ 9.7 cm2 to one of 200 +/‐ 38 cm2 per organ. An increase in epithelial cell membrane contributed to, but did not fully explain, the increase in microvillous area. No differences in mean cell height or mean cell volume were found but the average cell in the low‐NaCl birds was better developed in possessing a greater surface area of microvilli. On the high‐NaCl diet, the epithelium was 33 +/‐ 2.7 microns tall and contained about 270 +/‐ 15 million cells. Each cell had a volume, on average, of 540 +/‐ 59 microns 3 and a microvillous surface of 32 +/‐ 2.6 microns 2. After NaCl depletion, there were 420 +/‐ 75 million cells and the average microvillous surface was 49 +/‐ 5.3 microns 2 per cell. The morphological adaptations alone do not explain the increased net Na transport found on the low‐NaCl diet. Of cardinal importance is greater density of open Na channels in apical cell membranes.
Permeability of blood‐brain and blood‐nerve barriers in experimental diabetes mellitus in the anaesthetized rat
Authors: Bradbury MW , Lightman SL , Yuen L , Pinter GG
Published: December 2014

Diabetes was induced with streptozotocin in rats weighing about 160 g. These were maintained with age‐matched controls for up to 14 months, blood glucose being periodically monitored. Half the diabetic and control rats received the aldose reductase inhibitor, Ponalrestat, in their diet. At 3 weeks, 6‐7 months and 13‐14 months, the vascular permeability in regions of brain, and in optic and sciatic nerves, were measured by maintaining radiotracers in the bloodstream‐‐125I‐albumin (100 min), [14C]sucrose (60 min) and 131I‐albumin (5 min)‐‐followed by tissue sampling and counting at termination. 131I‐albumin estimated residual intravascular plasma. Diabetes of up to 13‐14 weeks caused no measurable increase in the sucrose permeability of microvessels in eight different brain regions, in optic or in sciatic nerve. At 3 weeks of diabetes, sucrose permeability in all brain regions and in optic nerve was reduced relative to that in controls. Extravascular albumin entry into different regions of brain and optic nerve was insignificant and insensitive to diabetes, except in the hypothalamus and optic nerves where it was raised with increasing duration of diabetes. In sciatic nerve, extravascular albumin distribution was markedly increased by diabetes, but sucrose permeability was not demonstrably affected. At the level used in the diet, Ponalrestat reduced the sorbitol content of diabetic sciatic nerve but did not protect again the increased permeability to albumin.
A two‐dimensional morphometry‐based model of interstitial and transcapillary flow in rabbit synovium
Authors: Levick
Published: December 2014

The synovial lining of a joint is a layer of specialized connective tissue, containing fenestrated capillaries, that regulates the volume and composition of fluid in the joint cavity. The hydraulic conductance of the synovial lining and of the plasma‐to‐cavity pathway is increased by high intra‐articular pressures (IAP greater than 9 cmH2O) and this is accompanied by an increase in the interstitial pathway's area/pathlength ratio. In order to assess the contribution of the altered pathway geometry to the conductance changes, and also to evaluate the conductivity of the synovial interstitial matrix (Ki) and local flow patterns, a two‐dimensional model of trans‐synovial flow was developed from morphometric data at low IAP (5 cmH2O) and high IAP (25 cmH2O). Darcy's law was applied to finite elements within a ‘unit cell’ of synovium to compute a steady‐state pressure field. Elements adjacent to limited discrete porous regions of the capillary wall were additionally subjected to the Starling principle. Appropriate values of Ki and capillary wall conductance were obtained by iteration to match the experimentally measured net conductances. The value of Ki that matched the data at low IAP was 1.4‐2.1 x 10(‐12) cm4 s‐1 dyn‐1 (1.4‐2.1 x 10(‐15) m4 s‐1 N‐1). This is in the range reported for some other fluid‐confining tissues, namely scleral stroma and aortic wall. Comparison between a capillary model with localized porous regions and one with a uniformly distributed permeability showed that the uniformity assumption (commonly used in mathematical modelling) leads to severe underestimation of the local pericapillary pressure gradients. At high IAP, synovial deformation was found to account for 24‐50% of the increased hydraulic conductances. To explain the remainder, it was necessary to postulate a rise in Ki, especially in the zone between the joint cavity and capillary wall. Possible mechanisms involving tissue hydration and/or glycosaminoglycan wash‐out at high IAP are discussed. The model highlights a need for quantitative biochemical analysis.
Evidence for volume regulatory increase by Na‐K‐Cl co‐transport in rat arterial smooth muscle
Authors: Chipperfield AR , Davis JP , Harper AA
Published: December 2014

A component of K efflux (86Rb as tracer) from rat femoral arterial smooth muscle was blocked by loop diuretics. Following hypertonic challenge with 100 mM‐sucrose, K efflux increased but not in the presence of loop diuretics. This is taken as evidence for a volume regulatory increase mediated by Na‐K‐Cl co‐transport.
Regional characteristics of intestinal iron absorption in the guinea‐pig
Authors: Chowrimootoo G , Debnam ES , Srai SK , Epstein O
Published: December 2014

Features of iron absorption by the upper small intestine and ileum in the adult guinea‐pig have been compared. Autoradiographic methods have revealed that whilst only upper villus enterocytes in the duodenum‐jejunum are involved in brush‐border uptake, the entire villus epithelium in the ileum displays this function. Consistent with these results was the finding that brush‐border membrane vesicles prepared from ileal mucosa demonstrated a higher capacity for iron uptake (expressed per mg protein) compared to vesicles of duodenal origin. Iron transport to blood following 30 min exposure of mucosa to 59Fe‐ascorbate was some elevenfold higher in upper, compared to lower, small intestine. The relevance of these findings to our knowledge of the cellular processes involved in intestinal iron absorption and its regional localization is discussed.
A diet enriched in essential fatty acids protects against the loss of lymphocytes which occurs in rats suffering from streptozotocin‐induced diabetes
Authors: Oon BB , Muggleston D , Warley A
Published: December 2014

Blood glucose, circulating lymphocyte numbers, and the percentage of T‐ and B‐lymphocytes were measured in diabetic and non‐diabetic rats which had been fed on control diets, or diets which included oil of evening primrose or coconut oil. In diabetic animals fed on the control or coconut oil diet the number of circulating lymphocytes decreased; this was caused by a decrease in both T‐ and B‐lymphocytes. The decreases in lymphocyte numbers was less in the diabetic animals fed on the diet enriched in evening primrose oil. In these animals the decrease in T‐lymphocytes was less and the percentage of B‐lymphocytes was increased. It is suggested that the diet enriched in evening primrose oil exerts its protective effect by providing gamma‐linolenic acid which is necessary for biosynthesis of prostaglandin E1.
Interaction between secretin and cholecystokinin‐octapeptide in the exocrine rat pancreas in vivo and in vitro
Authors: Singh J , Lennard R , Salido GM , Wisdom D , Render CL , Pozo MJ , Pariente JA , Camello PJ
Published: December 2014

This study investigates the interaction between physiological doses of the synthetic gut hormones, cholecystokinin‐octapeptide (CCK8) and secretin on pancreatic juice secretion in the anaesthetized rat and on amylase secretion and Ca2+ and Mg2+ mobilization in isolated pancreatic segments and acinar cells. CCK8 (150 pmol kg‐1 h‐1) and secretin (100 pmol kg‐1 h‐1) evoked marked time course increases in pancreatic juice flow, total protein output and amylase secretion in the anaesthetized rat when administered separately compared to saline controls. Simultaneous intravenous infusion of CCK8 and secretin did not yield either an additive response or a potentiation but instead it caused a decrease in secretory responses. Administration of either polymyxin B (10(−8) mol kg‐1 h‐1) or staurosporine (10(−8) mol kg‐1 h‐1), two protein kinase C inhibitors, simultaneously with both CCK8 and secretin caused a further decrease in all secretory parameters. Superfusing pancreatic segments with either CCK8 (10(−11) M) or secretin (10(−11) M) elevated amylase output compared to the smaller response with a combination of CCK8 and secretin. Combining staurosporine (10(−6) M) with CCK8 and secretin resulted in a further decrease in amylase output. CCK8 (10(−11) M) evoked a large increase in radiolabelled Ca2+ influx into pancreatic segments and elevated cytosolic free Ca2+ concentration ([Ca2+]i) in acinar cells loaded with the fluorescent dye, Fura‐2. Secretin (10(−11) M) alone had no significant effect on Ca2+ mobilization but it markedly attenuated the increases in radiolabelled Ca2+ influx and [Ca2+]i elicited by CCK8. In superfused pancreatic segments CCK8 (10(−11) M) evoked a net efflux of Mg2+ whereas secretin (10(−11) M) induced a net uptake of Mg2+. Combining secretin with CCK8 also resulted in a net uptake of Mg2+. The results indicate that both Ca2+ and Mg2+ mobilization may be associated with the interaction between CCK8 and secretin in the rat pancreas.
Effect of potassium on ventilation in the rhesus monkey
Authors: Paterson DJ , Dorrington KL , Bergel DH , Kerr G , Miall RC , Stein JF , Nye PC
Published: December 2014

Increasing the concentration of arterial plasma K+ to 6–8 mM increased ventilation in two sedated analgesic‐treated rhesus monkeys who had their end‐tidal CO2 held constant during euoxia (arterial oxygen pressure, Pa,O2, ca 100 Torr) and hypoxia (Pa,O2, ca 40 Torr). During euoxia and hypoxia, hyperkalaemia increased ventilation up to 40 and 250%, respectively. This effect was reduced in euoxia and virtually abolished in hypoxia following an abrupt switch to 100% oxygen. Thus the ventilatory response of this primate to hyperkalaemia is at least as sensitive as that of the cat and if hypoxia is added the two stimuli generate a powerful drive to breathing.
Mobilization of calcium by the brief application of oxytocin and prostaglandin E2 in single cultured human myometrial cells
Authors: Thornton S , Gillespie JI , Greenwell  , Dunlop W
Published: December 2014

Intracellular calcium ([Ca2+]i) mobilization was studied in single cultured human myometrial cells in response to the agonists oxytocin and prostaglandin E2 (PGE2) using the fluorescent dye Fura‐2. Oxytocin and PGE2 applications were associated with an increase in [Ca2+]i, although there was a marked intercell variation in the amplitude of the agonist‐induced response. Removal of extracellular calcium ([Ca2+]o) reduced the oxytocin‐induced rise and abolished the PGE2‐induced rise in [Ca2+]i, thereby demonstrating that oxytocin but not PGE2 can mobilize intracellular stores of calcium. In nominally calcium‐free medium, [Ca2+]i was not increased by PGE2 but subsequent application of oxytocin increased [Ca2+]i, thereby demonstrating that, within a single cell, calcium stores were mobilized by oxytocin and not PGE2. The intracellular calcium stores were completely depleted by a single application of oxytocin and not replenished in the absence of [Ca2+]o. Perfusion with calcium‐containing medium for 100 s enabled store refilling. Cell depolarization by 140 mM‐K+ caused a transient increase followed by a sustained elevation of [Ca2+]i on which were superimposed small fluctuations. Oxytocin caused an influx of calcium in cells depolarized by K+. This was more marked than that obtained with PGE2.
Modulation by peripheral conditioning stimuli of the responses of trigeminal brain stem neurones and of the jaw opening reflex to tooth pulp stimulation in chronically prepared, anaesthetized cats
Authors: Banks D , Kuriakose M , Matthews B
Published: December 2014

The effects of peripheral conditioning stimuli on the thresholds of the jaw opening reflex (JOR) and of trigeminal brain stem neurones to tooth pulp stimulation were examined in chronically prepared, anaesthetized cats. High intensity electrical conditioning stimuli applied to the ipsilateral forepaw produced an increase in the thresholds of both responses, with the JOR thresholds being elevated significantly more, and remaining elevated for significantly longer, than those of the neurones. These findings suggest that the elevation of the JOR cannot be explained just by inhibitory effects on the brain stem neurones.
Prostaglandin E2 in adipose tissue extracellular fluid of sheep
Authors: Thompson GE , Vernon RG
Published: December 2014

Prostaglandin E2 concentration in perfusate from microdialysis tubing implanted in subcutaneous adipose tissue of sheep did not consistently change during feeding. Noradrenaline infused into this tissue produced a prompt increase of glycerol concentration in the perfusate, but this changed to a slight decrease towards the end of the infusion. At approximately the time of this decrease, levels of prostaglandin E2 in the perfusate increased.
Parathyroid hormone‐related peptide increases urinary phosphate excretion in fetal lambs
Authors: Davicco MJ , Coxam V , Lefaivre J , Barlet JP
Published: December 2014

The effect of synthetic human parathyroid hormone‐related peptide fragment 1–34 (hPTHrP) on plasma concentration and urinary excretion of inorganic phosphorus (P) was compared to that of synthetic bovine PTH fragment 1‐34 (bPTH) in four 120‐ to 130‐day‐old fetal lambs chronically catheterized in utero. They received by I.V. infusion according to a Latin square design either bPTH (6 nmol per fetus) or hPTHrp (6 nmol per fetus) alone, or after the synthetic analogue [Tyr34]bPTH(7–34)NH2 (12 nmol per fetus). Control fetuses received the same volume of solvent alone. Both bPTH and hPTHrP stimulated diuresis. They induced hypercalcaemia, hyperphosphaturia and hypophosphataemia. The effects of hPTHrP were inhibited by [Tyr34]bPTH(7–34)NH2, indicating that PTHrP might work through the PTH receptor.
Microvillus growth and M‐cell formation in mouse Peyer's patch follicle‐associated epithelial tissue
Authors: Smith MW , Peacock MA
Published: December 2014

Development of microvillus structure on the surface of enterocytes migrating over follicle‐associated lymphoid tissue appears to take place in an identical way to that seen on villus enterocytes. M‐cells, which are not found in crypts, possess microvilli of constant length in all parts of the follicle dome epithelial tissue. The surface area of M‐cell microvilli is not however different from that determined on fully formed follicle‐associated enterocytes. These results support the hypothesis that M‐cell formation takes place throughout the dome epithelium by immune‐induced transformation of already existing enterocytes.
Coronary flow and left ventricular pressure during diastole in the anaesthetized dog
Authors: Gattullo D , Linden RJ , Losano G , Pagliaro P , Westerhof N
Published: December 2014

There is controversy about the effect of left ventricular pressure on resistance of the intramyocardial coronary vessels. In anaesthetized dogs the effect of left ventricular pressure on coronary flow during diastole was studied using an extracorporeal circulation and allowing the heart to contract and relax isovolumically. At constant coronary perfusion pressure of about 45 mmHg with maximal coronary vasodilatation, produced by dipyridamole, increases in diastolic left ventricular pressure to 22 mmHg, producing a volume of 50 ml, did not affect diastolic coronary flow. It is suggested that in the intact animal over the physiological range of left ventricular diastolic pressure the resistance in the coronary vessels is not affected.
Diversity and homogeneity within endplates associated with physiologically identified static gamma‐axons in cat tenuissimus muscle
Authors: Arbuthnott ER , Gladden MH , Sutherland FI
Published: December 2014

The terminations of static gamma‐axons on chain fibres may be associated with a muscle surface contour thrown into complex folds at one extreme, ranging through lesser degrees of folding to being apparently uninfluenced by the presence of the terminals. The folding is not necessarily confined to the postsynaptic membrane. As a quantitative indicator of the degree of folding seen in cross‐sections, the perimeters of the two halves of the intrafusal fibre with, and without the ending were compared. Both complexity of endplate structure and an undifferentiated appearance could co‐exist within individual endings (of six static gamma‐axons on thirteen chain fibres), associated with axons that supplied only chain fibres in the spindle isolated. (It should be noted, however, that the type of intrafusal fibres innervated by a particular axon was definitively identified only for the spindle isolated.) Endings of three other static gamma‐axons on six chain fibres had a more homogeneous and less complex endplate structure; these supplied bag2 fibres in addition to the chain fibres and their endplates on the bag2 fibres were less folded than those of three axons which supplied bag2 fibres only. A sensory inhibitory influence on folding was not apparent because complexly folded endplates on chain fibres lay close (less than 500 microns) to sensory endings. All the endings studied were functional. In our experimental conditions all nine static gamma‐axons which innervated chain fibres, alone, or together with a bag2 fibre, drove the Ia afferent at some stimulus frequencies; none of the three static gamma‐axons innervating bag2 fibres alone caused driving at any frequency. These findings are discussed in relation to the concept of a dynamic remodelling of ending structure during life, to the relationship between the motor axon and the intrafusal fibre it innervates, and to the possibility that subgroups of static gamma‐motoneurones might exist which could release different amounts of the trophic substances responsible for moulding the endplate structure.
Reflex vascular responses to changes in left ventricular pressures, heart rate and inotropic state in dogs
Authors: al-Timman JK , Hainsworth R
Published: December 2014

Dogs were anaesthetized with chloralose, artificially ventilated and the chests widely opened. Left ventricular mechanoreceptors, including those in or near the coronary arteries, were stimulated by changing the pressure in the aortic root. The pressures distending the left atrium and the aortic and carotid baroreceptors were controlled. Reflex vascular responses were assessed from changes in perfusion pressures to a hind limb and to the rest of the systemic circulation, which were perfused independently at constant flows. Physiological increases in peak left ventricular and coronary arterial pressures resulted in vasodilatation in both regions. These responses were not influenced by changes in the heart rate. Stimulation of the left cardiac sympathetic nerves resulted in increases in peak ventricular pressure and in the maximal rate of change of pressure (dP/dtmax). This also resulted in increases in perfusion pressures (vasoconstriction) at all levels of peak ventricular pressure although there was little effect on the responses to changes in ventricular pressure. Sympathetic stimulation had little effect on the relationship between perfusion pressures and aortic root pressure. Increases in ventricular filling also resulted in vasoconstriction at all levels of peak ventricular pressure. Increases in filling, however, did not affect the relationship between either perfusion pressure and aortic root pressure. Conversely, decreases in left ventricular filling, by bypassing some of the left atrial blood, resulted in vasodilatation at all levels of peak ventricular pressures but had no effect on the perfusion pressures at any aortic root pressure. The combination of sympathetic stimulation with decreased ventricular filling resulted in little effect on perfusion pressures or on their responses to changes in either aortic root or ventricular systolic pressures. We conclude that the vascular responses to stimulation of left ventricular mechanoreceptors are not enhanced by sympathetic stimulation, decreases in ventricular filling or the combination of the two. The apparent effects of each of these interventions alone on the relationships between perfusion pressures and ventricular, but not aortic root, pressure, could be explained if the receptors responsible were sensitive more to changes in aortic root and coronary arterial pressures than to pressure changes in the ventricle itself.
The effects in the rat of two fragments of parathyroid hormone‐related protein on uterine contractions in situ
Authors: Barri ME , Abbas SK , Care AD
Published: December 2014

Synthetic parathyroid hormone fragment PTH(1–34) has been reported recently to inhibit uterine contractions stimulated by a variety of agonists. We have studied the effect in this system of the parathyroid hormone‐related protein fragment PTHrP(1–34) which shows 60% homology with PTH over the first thirteen amino acid residues. The effects of two different PTHrP fragments on acetylcholine‐stimulated uterine contractions in vitro were studied. Whereas synthetic hPTHrP(75–86 amide) (10(−9)−10(−7) M) was without effect, synthetic hPTHrP(1–34) (10(−9)−10(−7) M) was capable of inhibiting, in a dose‐related fashion, uterine muscle contractions precontracted with 10(−6) M‐acetylcholine. In a second series of experiments the bovine PTH(3–34) fragment itself was shown to have no stimulatory effect on acetylcholine‐stimulated contractions. Also this fragment in an equimolar concentration (10(−7) M) failed to antagonize the effects of PTHrP(1–34) on acetylcholine‐stimulated uterine contractions. However, a 100‐fold excess molar concentration of bPTH(3–34) (10(−6) M) completely abolished the inhibitory action of hPTHrP(1–34) (10(−8) M) on acetylcholine‐stimulated uterine contractions. These results clearly show that the inhibitory action of PTH(1–34) and PTHrP(1–34) on uterine contractions depends on the integrity of the amino‐terminal region of the molecule.
Evidence for involvement of nitric oxide in the non‐adrenergic non‐cholinergic (NANC) relaxation of human lower oesophageal sphincter muscle strips
Authors: McKirdy HC , McKirdy ML , Lewis MJ , Marshall RW
Published: December 2014

Electrical field stimulation of circular muscle strips from human lower oesophageal sphincter reveals a predominant relaxation response. This relaxation is non‐adrenergic non‐cholinergic (NANC). The nitric oxide synthesis‐blocking agent N omega‐nitro‐L‐arginine (10‐100 microM) reduces or abolishes this NANC relaxation, suggesting involvement of nitric oxide in the response.
Involvement of carbonic anhydrase in ammonia flux across rumen mucosa in vitro
Authors: Bodeker D , Oppelland G , Holler H
Published: December 2014

Carbonic anhydrase activity in mucosa of the sheep rumen wall was completely inhibited by acetazolamide and ethoxyzolamide. This inhibition significantly reduced ammonia flux across mucosal discs in vitro but was ineffective if short‐chain fatty acids were present in the bathing solution. The findings are discussed in relation to the mechanism of ruminal ammonia absorption.