bluuebunny/crossref_metadata_2025 huggingface dataset:
Uridine transport in human erythrocytes: data from normal subjects and from patients with renal failure
Authors: Fervenza FC , Meredith D , Ellory JC , Hendry BM
Published: December 2014

Erythrocyte uridine transport has been studied in eight normal individuals and eight patients on haemodialysis for chronic renal failure. The initial rate of zero‐trans uridine influx at 37 degrees C has been measured as a function of extracellular uridine concentration using [14C]‐labelled uridine. The results are consistent with Michaelis‐Menten kinetics. In normal humans the mean Vmax for uridine influx was 32.8 +/‐ 6.4 mumol (1 cells)‐1 s‐1 (mean +/‐ S.D.) and the mean Km was 190 +/‐ 12.3 microM. The measurements made in renal failure patients were not significantly different (mean Vmax 30.1 +/‐ 7.1 mumol (1 cells)‐1 s‐1, mean Km, 185 +/‐ 13.2 microM). These results are discussed with reference to the reported data on uridine transport in human erythrocytes at temperatures between 4 and 35 degrees C; it is suggested that zero‐trans uridine influx shows a decrease in temperature dependence above 25 degrees C. The Vmax for zero‐trans uridine influx at 37 degrees C in normal erythrocytes represents a turnover number for the nucleoside transporter of 180 uridine molecules per second.
The effect of a rumen microbial fermentation on urea and nitrogen metabolism of sheep nourished by intragastric infusion
Authors: Whitelaw FG , Milne JS , Chen XB
Published: December 2014

Four sheep were maintained by infusion of volatile fatty acid (VFA), mineral and buffer solutions to the rumen and casein to the abomasum. After a 3 week period in which control measurements were made, glucose was introduced gradually to the rumen infusion mixture until glucose replaced about 65% of VFA energy. Further measurements were made in the fourth week of glucose additions after which the control VFA infusions were re‐established and measurements repeated. Urea kinetics were measured with [14C]urea. Rumen ATP concentrations were used as an index of microbial growth and increased from 1.5 nmol ml‐1 on control treatments to 46 nmol ml‐1 when glucose was given. The presence of a rumen fermentation resulted in a 40% decrease in plasma urea concentration but was without effect on rumen ammonia concentration. Urea irreversible loss rate decreased from 18.0 to 12.8 g urea day‐1 when glucose was given. This, however, was matched by a decrease in urinary urea excretion, with the result that urea degradation, obtained by difference, remained constant throughout the three treatment periods. Daily nitrogen (N) retention increased from 1.0 to 2.7 g when a rumen microbial population was present. A model of urea and NH3 transactions for the two dietary situations is presented. Calculations indicated that 0.40 of the casein N supply was reutilized as urea by the rumen micro‐organisms. It is suggested, however, that the improvement in N retention resulted from a change in protein:energy ratio of the infused nutrients rather than from an enhanced supply of protein to the intestine. The use of endogenous urea clearance as an index of epithelial permeability to urea is questioned.
Mechanisms of phosphate transport in sheep intestine and parotid gland: response to variation in dietary phosphate supply
Authors: Shirazi‐Beechey SP , Beechey RB , Penny J , Vayro S , Buchan W , Scott D
Published: December 2014

The transport of phosphate in intestinal brush‐border membrane and parotid basolateral membrane vesicles isolated from sheep maintained on high and low phosphate diets have been studied. The mechanism of the transport of phosphate in the intestine is via a proton symporter whilst in the parotid gland it is effected by a Na+ coupled transporter. In sheep fed a low‐P diet there is no change in the capacity of the parotid basolateral membrane to transport phosphate into the parotid end piece cells. This is in marked contrast to the response of the enterocyte brush‐border membrane, where there is a significant enhancement of the capacity of the membrane to transport phosphate. We conclude that in sheep the gut appears to play a major role in response to phosphate deprivation, by increasing the capacity to transport phosphate. This enhancement is not achieved by increases in the levels of circulating 1,25‐dihydroxycholecalciferol.
Okadaic acid, a protein phosphatase inhibitor, increases the calcium transients in isolated ferret ventricular muscle
Authors: Lee JA , Takai A , Allen DG
Published: December 2014

Okadaic acid is a protein phosphatase inhibitor which has been found to produce a marked positive inotropic effect in isolated cardiac muscle. Using aequorin‐injected ferret papillary muscles, we demonstrate that the increase in tension seen with okadaic acid is accompanied by a simultaneous increase in the amplitude of the calcium transients. By comparison with the effects of changing the extracellular calcium concentration, it is shown that the increase in calcium transient amplitude can account for the inotropic effect of okadaic acid.
Comparison of a single‐injection technique and inulin clearance for determining glomerular filtration rate in the sheep
Authors: Wholohan T , Yesberg NE , Cross RB
Published: December 2014

Glomerular filtration rate (GFR) was assessed over a 2 h period by the clearance of inulin (Cin) and in the subsequent 2 h period by a single‐injection technique using radiolabelled sodium iothalamate (Ciot) or chromium‐EDTA (CEDTA). Regression analysis yielded a significant correlation (P less than 0.05) between the standard clearance technique and the single‐injection method, with the relationship Ciot = ‐10.67 + 1.25Cin with a significant correlation coefficient of r = 0.71 (P less than 0.02). There was better agreement between clearance values of inulin measured on successive days than between values determined by the single‐injection technique on successive days. Cin remains the method of choice in sheep.
Are there more than two types of alpha‐adrenoceptors involved in physiological responses?
Authors: Wilson VG , Brown CM , McGrath JC
Published: December 2014

The application of the four main techniques available for examining the properties of alpha‐adrenoceptors, gene coding, radioligand, biochemical and functional methods, has reinforced the earlier subclassification (alpha 1‐ and alpha 2‐subtypes). These different techniques have not yet yielded subclassifications which entirely align when the subtypes have been examined in detail, although a prime reason for this is that the different techniques have not yet all been applied to the same receptors. There is evidence available on each level to indicate that there are further subtypes within the alpha 1‐ and alpha 2‐adrenoceptors as originally defined pharmacologically, with the possible exception of functional evidence at cellular and tissue level for subtypes of alpha 2. The present extension of the subclasses to three each (A,B,C) for alpha 1 and alpha 2 does not withstand cross‐examination on every level and seems unlikely to withstand further probing. It remains true that the set of subtypes of alpha‐adrenoceptor which can be activated or blocked by drugs in functioning intact tissue preparations and which are shown in Fig. 4 has not been added to by knowledge derived from ligand binding or molecular biology. These techniques have bolstered confidence in the existing functioning categories and have enabled acceleration of drug screening programmes to find new, potent, highly selective antagonists for the known receptors. Rather than taking the categorization of receptors away from the recognition site to the larger molecule, they have reinforced its supremacy. The advantages being gained from the molecular biology of receptors lie in understanding cell signalling and, on the wider genetic scale, on the place of the receptors, among other elements of the cell, in regulation and function within the organism. From the physiologist's point of view, classical pharmacology can still be relied on as the basis for understanding the specificity of drugs which activate or block plasmalemmal receptors and to keep the numbers of these receptors within reason, while molecular biology may increasingly provide the tools to study the subsequent physiological events. A few years ago, one of us commented (in jest!) that the availability of so many different techniques for examining the properties of alpha‐adrenoceptors may eventually provide the ultimate answer that there are forty‐two subtypes, but that along the way, the original reason for requiring classification might become lost (McGrath, 1983 b).(ABSTRACT TRUNCATED AT 400 WORDS)
The effects of neuromuscular stimulation on muscle tone at the knee in paraplegia
Authors: Douglas AJ , Walsh EG , Wright GW , Creasey GH , Edmond P
Published: December 2014

Resting muscle tone of the leg was measured in terms of thigh muscle stiffness and knee resonant frequency in muscles of spinal cord injured subjects who had been involved in an electrical neuromuscular stimulation training programme of the thigh muscles over at least 2 months. The thigh circumference of these patients was 6.6% larger than before training commenced (P less than 0.001) and showed increased muscle stiffness and resonant frequency compared to a similar group of paralysed subjects who had not used any neuromuscular stimulation. Resonant frequency and stiffness after the long‐term training were similar to those of non‐injured controls and therefore the stimulation programme seemed to reverse the effects of paralysis on muscle tone. Short periods of rest (30 min) caused increased muscle stiffness in non‐injured controls and paralysed muscles trained by neuromuscular stimulation. Additional 15 min periods of neuromuscular stimulation further increased muscle stiffness in the trained muscles but also in the muscles of paralysed subjects who had no long‐term neuromuscular training. In contrast, 15 min sessions of passive movement of the knee decreased muscle stiffness in long‐term trained paralysed muscles and untrained paralysed muscles. Knee resonant frequency was also significantly decreased in the trained paralysed muscles. Results show that muscle tone varies depending on the amount of previous movement or rest and that although neuromuscular stimulation of paralysed muscles increases muscle stiffness and knee resonant frequency, it is in fact restoring such properties of the muscle to a state approaching that of non‐injured controls.
Electrical fields, nerve growth and nerve regeneration
Authors: McCaig CD , Rajnicek AM
Published: December 2014

The presence of voltage gradients within developing and damaged tissues led to the notion that the resultant electrical fields provide instructional cues to cells. Field effects on avian and amphibian neurones in vitro include increased differentiation, turning of neurites towards the cathode, increased rate of growth towards the cathode, resorption of anodefacing neurites, increased branching and increased filopodial activity. Electric fields enhance regeneration of damaged PNS and CNS neurones in animals as diverse as lampreys, frogs, rats and guinea‐pigs, but the mechanisms by which fields produce their effects are not understood. Further examination of the interaction of fields with intracellular elements, such as the cytoskeleton and second messenger systems, may offer some insight.
Cerebral blood flow in the anaesthetized immature sheep fetus and the response to hypercapnia
Authors: Habgood MD , Jones SE , Maroni JM , Pickard JD , Richards HK , Saunders NR
Published: December 2014

Regional cerebral blood flow (CBF) has been measured in eight anaesthetized, exteriorized, fetal sheep between 58 and 62 days gestation; four were controls, four were hypercapnic (PaCO2 = 78 +/‐ 5 mmHg, mean +/− S.E.M.). Blood flow values were calculated from quantitative autoradiography following the infusion of [14C]iodoantipyrine into a cannulated fetal placental vein, for the cerebellum, medulla, and five layers of the developing neocortex: cortical plate (CP), subplate zone (SP), intermediate zone (IZ), subventricular zone (SV), and the ventricular zone (VZ). The highest control CBF rates were recorded in the cortical plate (49.3 +/‐ 7.4 ml min‐1 (100 g)‐1, mean +/− S.E.M., posterior cortex) and in the ventricular zone (40.5 +/− 4.8, posterior cortex), which at this stage of development are the regions of greatest cell density. The lowest CBF rates were recorded in the subplate zone (23.8 +/− 6.8, anterior cortex) and in the intermediate zone (23.4 +/− 7.6, anterior cortex), which are the regions of lowest cell density. Experimentally induced hypercapnia increased CBF in all brain regions and enhanced the regional pattern of flow. The results provide evidence that CBF in the immature fetal sheep brain (at 58–62 days gestation) is heterogeneous under both control and hypercapnic conditions (especially in the neocortex). Blood vessels of the fetal sheep brain at this early stage of development are clearly responsive to CO2.
Unidirectional transport of glucose and lactate into brain of fetal sheep and guinea‐pig
Authors: Bissonnette JM , Hohimer AR , Chao CR
Published: December 2014

The first‐passage multiple‐indicator dilution method was used to measure blood to brain transport of D‐ and L‐glucose, D‐ and L‐lactate and sucrose relative to 22Na, an impermeable reference tracer, in fetal sheep. Fractional extraction for D‐glucose was 0.315 +/− 0.051 (S.E.M.) at normal glucose levels and fell to 0.198 +/− 0.041 at 5.2 +/− 0.4 mM‐glucose. Fractional extractions for L‐glucose, D‐ and L‐lactate and sucrose were not different from zero. No specific blood‐brain transport system was detected for L‐lactate in fetal sheep in vivo (fractional extraction = ‐0.024 +/− 0.019). Uptake of L‐lactate into isolated microvessels from fetal sheep cerebrum in vitro showed a slightly higher rate (32.2 +/− 8.9 pmol min‐1 (mg protein)‐1) than that for D‐lactate (22.6 +/− 5.6). In fetal guinea‐pigs, the carotid arterial injection method with tritiated water as the permeable reference was used to measure the brain uptake index (BUI). BUI was determined for D‐glucose (0.304 +/− 0.065) sucrose (0.008 +/− 0.001), L‐lactate (0.418 +/− 0.112) and D‐lactate (0.071 +/‐ 0.024). Unidirectional influx calculated from these measurements and estimates of cerebral blood flow showed that transport would be rate‐limiting for cerebral glucose utilization at arterial glucose levels below 0.5 mM in fetal sheep and 1.7 mM in fetal guinea‐pig. In fetal sheep, but not in fetal guinea‐pigs, lactate efflux may be limited by brain‐blood transport.
The cholinergic regulation of potassium (86Rb+) permeability in sweat glands isolated from patients with cystic fibrosis
Authors: Wilson SM , Pediani JD , Cockburn F , Bovell DL , Jenkinson DM , Paton JY , Coutts J , Davidson R , Lambert J , Morris G , et al.
Published: December 2014

Sweat glands isolated from skin obtained from normal subjects and patients with cystic fibrosis (CF) were pre‐loaded with 86Rb+ and superfused with a physiological salt solution and the rate of 86Rb+ efflux was measured as an indicator of cellular potassium permeability. Acetylcholine always evoked a permeability increase in the glands from control subjects and this response could be resolved into calcium‐dependent and calcium‐independent components. Sweat glands from CF patients did not show such consistent responses. In three individuals the glands were abnormally insensitive to acetylcholine but normal responsiveness was seen in a fourth case. It is proposed that CF can induce dysfunction of calcium‐dependent control processes in sweat glands.
Conductance rise induced by the calcium ionophore A23187 in unfertilized eggs of tilapia
Authors: House CR
Published: December 2014

Current‐clamp measurements on unfertilized tilapia eggs gave linear current‐voltage relations in the range 0 to ‐120 mV. Eggs had low resting potentials (‐22 mV) and high specific membrane resistances (500 k omega cm2) and specific membrane capacitances (0.9 microF cm‐2) indicating no marked folding of their plasma membrane. Application of A23187 induced a small depolarization and a conductance rise, the response having a reversal potential of about ‐16 mV. The results suggest that tilapia eggs have a calcium‐gated conductance probably activated at fertilization.
The role of calcitonin gene‐related peptide in gastric mucosal protection in the rat
Authors: Forster ER , Dockray GJ
Published: December 2014

The presence of circulating antibodies to calcitonin gene‐related peptide (CGRP) enhanced the damaging effect of ethanol on the rat gastric mucosa. Taken together with previous experimental and morphological data the results suggest that CGRP released from the peripheral terminals of visceral afferent fibres plays a role in mediating gastric mucosal defence mechanisms.
Catabolism of hyaluronan in rabbit skin takes place locally, in lymph nodes and liver
Authors: Laurent UB , Dahl LB , Reed RK
Published: December 2014

The catabolism of hyaluronan has been studied by injecting hyaluronan, labelled with 125I‐tyramine cellobiose (125I‐TC), subcutaneously into the hindpaw of rabbits. Following endocytosis, 125I‐TC remains in the cells at the site of uptake, allowing localization of the site of catabolism. At 6 h after subcutaneous injection, 65% of the injected radioactivity was recovered. The skin at the injection site contained 47%, the popliteal gland at the side of injection 10%, and the liver 8% of the injected dose. At 48 h the three organs contained 40% of the injected dose with 17% in the skin, 10% in the lymph node and 13% in the liver. The decline in recovery could be accounted for by urinary excretion of the tracer, implying that some tracer had been released from the cells after endocytosis. Chromatography revealed that over 85% of 125I‐TC‐hyaluronan in the lymph nodes and liver was of low molecular mass throughout the experiment. In skin, 4% of the injected tracer was recovered with low molecular mass at 6 h, increasing to 12% of injected dose at 24 and 48 h. Thus, a minimum of 12% of the injected tracer was catabolized per 24 h at the skin injection site. If cells in skin are responsible for the subsequent release of tracer, as seen from the decrease in recovery of the injected dose, another 10‐15% of the tracer could have been catabolized locally in the skin per day. The major part of the hyaluronan injected in the skin was, however, catabolized by lymphatic removal and subsequent degradation in local lymph nodes and liver.
Where in the muscle spindle is the resting discharge generated?
Authors: Proske U , Gregory JE , Morgan DL
Published: December 2014

This is a report of experiments on muscle spindles of the soleus muscle of the anaesthetized cat. Following a step shortening of the muscle, muscle spindles fall silent. At suitable muscle lengths their discharge may restart several seconds later to gradually recover a maintained rate of discharge. These experiments examine the question of where within the spindle the resumption of a resting discharge may originate. It was found that stimulation of some static fusimotor fibres immediately after the shortening led to early recovery of the resting discharge. Stimulation of dynamic and other static gamma motoneurones had much less effect. Since the dynamic gamma axons innervate almost exclusively the bag1 intrafusal fibre, contraction of this fibre appears to have little influence on the mechanisms responsible for restarting the resting discharge. Bag and chain fibres do seem to be involved. For primary endings, the bag2 fibre contraction was especially effective since static axons, which did not evoke ‘driving’ of the afferent response, and which are thought to predominantly innervate bag2 fibres, did restart the resting discharge. For secondary endings, stimulation of nearly all gamma axons led to an early restart of the resting discharge suggesting that here the nuclear chain fibres were responsible.
Arteriolar vasodilatation in frog skeletal muscle in vivo: modification of second messenger systems
Authors: Fuglsang A
Published: December 2014

This study was concerned with the role of cyclic nucleotides in the post‐junctional vasodilatation mechanism. Interventions with second messenger systems involving cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP), allowed the role of these nucleotides in vascular smooth muscle to be evaluated in the autoperfused, transparent frog muscle, m. cutaneous pectoris. The microcirculation was observed by intravital microscopy, and arteriolar diameters were continuously recorded. Pre‐ and post‐junctional effects were distinguished by comparing results in control frogs with those obtained in frogs that had been chemically sympathectomized with either 6‐hydroxydopamine or tetrodotoxin. Arterioles that were pre‐contracted with adrenaline dilated in response to topical application of forskolin or sodium nitroprusside, which are direct activators of intracellular adenylate cyclase and guanylate cyclase, respectively. Arterioles were also dilated by 3‐isobutyl‐1‐methylxanthine (IBMX), which is a non‐selective inhibitor of cyclic AMP‐ and cyclic GMP‐phosphodiesterase, and by rolipram, which is a selective inhibitor of the calcium‐independent cyclic AMP‐phosphodiesterase. Dibutyryl‐cyclic AMP and dibutyryl‐cyclic GMP also caused vasodilatation. These results indicate that in vascular smooth muscle, intracellular mechanisms involving cyclic nucleotides (cyclic AMP and cyclic GMP) are important in vasodilatation. They may act in conjunction with pre‐junctional inhibitory mechanisms on sympathetic nerves.
Primary cultures of guinea‐pig gall‐bladder epithelial cells suitable for patch‐clamp studies
Authors: O'Brien JA , James PS , Torre M
Published: December 2014

Cells derived from explants of guinea‐pig gall‐bladder maintained in culture for up to 14 days, exhibit a network of cytoskeletal filaments that are labelled by an anti‐cytokeratin antibody, but not by an anti‐desmin antibody, suggesting that they are of epithelial origin. These cells proved suitable for patch‐clamp studies and by using this method channels selective for K+ and Cl‐ were observed.
Intracellular pH and buffering power measured in isolated single cells from pregnant rat uterus
Authors: Eiesland J , Baro I , Raimbach S , Eisner DA , Wray S
Published: December 2014

Intracellular pH (pHi) affects smooth muscle function yet there have been few direct pHi measurements. Using the fluorescent indicator, 2',7'‐bis‐2‐(carboxyethyl)‐5(6)‐carboxyfluorescein acetoxymethyl ester, we report here the first measurements of pHi and buffering power (beta) in single, isolated, uterine smooth muscle cells. Mean pHi in cells from pregnant rat uteri was 7.09 +/‐ 0.08 (+/‐ S.E.M., n = 16 cells; 37 degrees C), and beta was found to be 12.8 +/‐ 2.8 mmol/l per pH unit (n = 15). The cells were able to regulate their pHi in the presence of butyrate when perfused in nominally CO2‐free solution.
Capillary filtration‐absorption balance reconsidered in light of dynamic extravascular factors
Authors: Levick
Published: December 2014

The evidence for the functional importance of extravascular Starling pressures now seems overwhelming, and when these terms are taken into account it is difficult to uphold the traditional conception that upstream microvascular filtration is largely matched by a sustained downstream reabsorption. Transient absorption can occur, however, during spontaneous vasomotion cycles, during sympathetic‐induced vasoconstriction and during hypovolaemic hypotension. Sustained absorption is possible in specialized tissues where the interstitium is ‘flushed’ by an independent stream (intestinal mucosa, renal cortex, lymph nodes). Both theory and experiment show, however, that absorption cannot be maintained across most low‐pressure exchange segments due to the finite permeability of microvessels to plasma protein, which leads to a rise in pericapillary interstitial oncotic pressure with time around absorbing microvascular segments. Extravascular hydraulic resistance may be a further determinant of net fluid transfer rate in situations where capillary wall resistance is low.
Effect of benzamil on sheep tracheal epithelium
Authors: Acevedo M , Olver RE , Ward MR
Published: December 2014

Apical membrane potential (Va), voltage divider ratio (f), transepithelial potential (Vt) and transepithelial resistance (Rt) were measured in isolated sheep tracheal epithelium. Individual membrane resistances and electromotive forces were calculated by a method described in the text. Whereas Va hyperpolarized and fa increased in tissues acutely exposed to amiloride or benzamil, the values for these parameters in tissues bathed for 1 h with mucosal benzamil (0.38 microM) were not significantly different from those found in control tissues. Circuit analysis revealed a higher value for both apical and basolateral membrane resistances in the benzamil‐treated tissues. These results suggest a decrease in the basolateral potassium conductance secondary to the initial decrease in the apical sodium conductance, thereby ensuring that the electrical driving force for other ions across the apical membrane is restored to normal in the face of a hyperpolarizing perturbation to the apical membrane.
Stretch‐induced increase of resting intracellular calcium concentration in single guinea‐pig ventricular myocytes
Authors: Le Guennec JY , White E , Gannier F , Argibay JA , Garnier D
Published: December 2014

Single guinea‐pig ventricular myocytes were loaded with the fluorescent Ca2+ indicator Indo‐1 AM and stretched by carbon fibres. Stretching increased resting tension. Sarcomere lengths were increased by 2‐18%. It was observed that a stretch increased resting [Ca2+]i in seven out of eight cells. The change in [Ca2+]i increased with the size of the stretch and returned to pre‐stretch levels on return to resting cell length. These observations suggest a means by which changes in resting muscle length can modify the contractile state of cardiac muscle.
Segmental heterogeneity of rat colonic electrogenic secretion in response to the bacterial enterotoxin Escherichia coli STa in vitro
Authors: Young A , Levin RJ
Published: December 2014

The effects of the bacterial toxin Escherichia coli STa on electrogenic secretion in proximal, mid and distal rat colon were examined in vitro using the short‐circuit current (Isc) as an index of secretion. All areas showed toxin‐elevated Isc which was reduced by bumetanide. The proximal colon was the most sensitive (lowest ED50) but displayed the lowest maximal increase in Isc, the mid colon had the largest maximal electrogenic response while the distal colon proved to be the least sensitive (highest ED50). Atropine (1 microM) and tetrodotoxin (1.25 microM) reduced the maximum Isc response to STa by up to 42%, indicating that the enteric nervous system may be partly involved in the response.
The effect of intracisternal injection of thyrotropin‐releasing hormone on gastric and duodenal motility in the urethane‐anaesthetized rat
Authors: Davison JS , Wootton P
Published: December 2014

Intracisternal injection of thyrotropin‐releasing hormone (TRH; 1‐3 micrograms) caused an increase in gastric motility and usually an inhibition of duodenal motility. These effects were abolished by vagotomy and atropine. No inhibition was seen even after tone and motility had been restored to a point at which vagal stimulation could evoke profound inhibition of gastric and duodenal motility. It is concluded that TRH is a specific activator of enteric excitatory pathways and that duodenal inhibition seen in control animals is a consequence of gastro‐duodenal inhibitory reflexes.
Opioidergic inhibition of reflexes evoked by selective stimulation of sural nerve C fibres in the rabbit
Authors: Clarke RW , Harris J , Ford TW , Taylor JS
Published: December 2014

Reflexes were evoked in the gastrocnemius medialis (GM) muscle nerve by selective electrical stimulation of the non‐myelinated C fibres of the ipsilateral sural nerve of decerebrated, spinalized rabbits. The opioid antagonist (‐)‐quadazocine (555 micrograms/kg i.v.) enhanced responses to sural C fibre stimulation to an average of 236% of pre‐drug levels. In addition, C fibre‐evoked reflexes were depressed for 7‐9 min after repetitive activation of the high threshold axons of the common peroneal nerve, and this effect was reversed after quadazocine. Thus, GM responses to stimulation of non‐myelinated sural afferent fibres are suppressed by endogenous opioid peptides, but the degree of inhibition does not appear to be as profound as that previously reported for reflexes evoked by myelinated fibres.
Characteristics of augmented breaths provoked by almitrine bismesylate in cats
Authors: Szereda‐Przestaszewska M , Jakus J , Stransky A , Barani H
Published: December 2014

The contribution of almitrine bismesylate to the occurrence and pattern of augmented breaths was studied in fifteen spontaneously breathing, anaesthetized cats. Breathing was via a tracheostomy, while the laryngeal resistance to airflow was measured with the larynx isolated in situ. Almitrine bismesylate at a dose of 0.5 mg kg‐1 of body weight was injected intravenously in the intact animals and following bilateral vagotomy which spared the right recurrent laryngeal nerve. Almitrine injected intravenously elicited augmented breaths within the first 45 s in thirteen cats and within 1 min in the remaining two cats. During augmented breaths inspiratory and expiratory airflows rose, the mean increases being 385.2 and 159.6% respectively above the controls (P less than 0.01). The inspiratory laryngeal resistance declined to 77.7% of the control (P less than 0.01) and expiratory laryngeal resistance increased by 95.4% above the control level (P less than 0.01). The inspiratory and expiratory times were prolonged by 56 and 58% compared with baseline breathing. Following the augmented breaths the respiratory airflows exceeded baseline values, the respiratory timing was slightly reduced, and the inspiratory laryngeal resistance was significantly lowered below the control level (P less than 0.01). The expiratory laryngeal resistance showed the same trend without statistical significance. Bilateral vagotomy abolished the occurrence of augmented breaths following almitrine injection.
Evidence for Na(+)−Ca2+ exchange and Ca(2+)−induced Ca2+ release in a cultured vascular smooth muscle cell line from the rat
Authors: Gillespie JI , Otun H , Greenwell  , Dunlop W
Published: December 2014

Measurements of intracellular calcium (Cai2+) and sodium (Nai+) have been made in single smooth muscle cells from the rat aortic cell line (A10) using the Ca(2+)‐ and Na(+)‐sensitive dyes Fura‐2 and SBFI (sodium‐binding benzofuran isophthalate). The effects of manipulation of intracellular and extracellular Na+ on Cai2+ have been investigated. Reversal of the Na+ gradient in control cells does not result in any measurable increase in Cai2+ or change in the rate of recovery of the cells from agonist stimulation, suggesting that there is little functional Na(+)‐Ca2+ exchange. In ouabain‐pre‐treated cells however, the recovery from agonist stimulation is significantly slowed, suggesting that in the presence of an elevated intracellular Na+ concentration there is an alteration in the Ca(2+)‐handling mechanisms. Reversal of the Na+ gradient in ouabain‐pre‐treated cells results in a transient increase in Cai2+ followed by a slow secondary rise. The transient component of this rise is absent on a second activation of the cell or by prior mobilization of the intracellular stores of Ca2+ by agonist. Data presented in this paper suggest the possibility that the transient component is due to a Ca(2+)‐induced Ca(2+)‐release mechanism triggered by an initial influx of Ca2+. The mechanism underlying this influx is not known but may involve the Na(+)‐Ca2+ exchanger operating in reverse. The possible modulation of the Na(+)‐Ca2+ exchanger and Ca(2+)‐induced Ca2+ release by internal Na+ is discussed.
Calcium oscillations in single isolated human vascular smooth muscle cells
Authors: Otun H , Gillespie JI , Greenwell  , Dunlop W
Published: December 2014

When cultured human vascular smooth muscle cells are exposed to sodium‐free solutions oscillations in intracellular calcium concentration are observed. In some cells the oscillations are maintained at constant amplitude throughout the exposure to Na(+)‐free solution, in others the amplitude of the oscillations falls to a lower, steady‐state level. The oscillations are also activated and maintained in isotonic, Na(+)‐free, K+ solutions suggesting that the underlying mechanism does not involve the opening and closing of voltage‐dependent channels. The possible mechanisms responsible for this behaviour are discussed.
Role of endothelium in the responses of human intracranial arteries to a slight reduction of extracellular magnesium
Authors: Szabo C , Hardebo JE , Salford LG
Published: December 2014

The effect of a slight reduction of extracellular magnesium on the tone of precontracted small human pial arteries and the dependence of the response on the functional integrity of the vascular endothelium was investigated in vitro. A decrease in extracellular magnesium from 1.2 to 0.8 mM resulted in sustained relaxation when the endothelium was intact. When the endothelium was disrupted, the same reduction resulted in an elevation of tone. These results suggest that small changes in extracellular magnesium modulate human cerebro‐arterial tone through an endothelium‐derived relaxing factor rather than by altering smooth muscle tone directly.
Electric field‐induced orientation of rat hippocampal neurones in vitro
Authors: Rajnicek AM , Gow NA , McCaig CD
Published: December 2014

Rat hippocampal neurones in primary culture exhibited directional growth in response to DC electric fields. Neurites lay perpendicular to the field after exposure to 28, 80 or 219 mV/mm but there was no orientation effect at 9 mV/mm or in unexposed control cultures. Fields that evoked perpendicular responses also reduced the number of cathode‐facing neurites. Orientation was the same for neurite initiation sites and the direction of overall neurite growth.
Abdominal chemo‐ and mechanosensitivity in ruminants and its role in the control of food intake
Authors: Forbes JM , Barrio JP
Published: December 2014

Ruminant animals have evolved a large and complex set of stomachs which allow fermentation of fibrous food by symbiotic micro‐organisms. These stomachs are well innervated and generate signals which are thought to be important in the control of voluntary food intake. Tension receptors in the muscular wall of the rumen and reticulum are slowly adapting and provide a measure of distension while epithelial receptors are rapidly adapting and provide information on the fibrousness of the digesta; they are involved in the control of stomach motility and voluntary food intake in order to prevent excessive distension. The epithelial receptors are also sensitive to the chemical nature of the digesta, particularly acidity. There are mechano‐ and chemoreceptors in the abomasum (true stomach) and duodenum and chemoreceptors in the liver, all of which have been implicated in the control of intake. It is relatively easy to prepare and maintain ruminants with a rumen fistula and many studies have shown the effects of such manipulations as distension of balloons in the rumen on voluntary intake. With fibrous, slowly digested feeds intake is primarily limited by rumen distension. With more rapidly digested feeds, however, the products of digestion play an important role in controlling intake. Short‐chain fatty acids are the main products of fermentation and infusion of their salts into the rumen depresses food intake to a much greater extent than infusion into the general circulation. Acetate or propionate given into the rumen are more effective, mole for mole, than butyrate but must be given at rates exceeding the natural rate of production in order to have a significant effect. It has been suggested that much of the effect of sodium acetate is via the increase in the osmolality of rumen fluid but there is considerable uncertainty as to the physiological significance of osmotic effects, especially when animals have free access to water and can prevent excessive increases in tonicity by increasing their water intake. Other constituents of rumen fluid have been implicated in the control of food intake, particularly lactic acid and nitrogenous compounds, especially as these can be found in fermented feeds such as silage. The omasum controls the flow of digesta to the abomasum; it is therefore well placed to control rumen fill and thus intake but there has been little study in this area and this is also true for the abomasum.(ABSTRACT TRUNCATED AT 400 WORDS)
Factors affecting the components of the alveolar CO2 output‐O2 uptake relationship during incremental exercise in man
Authors: Cooper CB , Beaver WL , Cooper DM , Wasserman K
Published: December 2014

The VCO2‐VO2 (alveolar CO2 output‐alveolar O2 uptake) relationship (V‐slope) during increasing work rate (ramp) cycle ergometer exercise has two approximately linear components: a lower component slope (S1) with a value of about 0.95 and a steeper, upper component (S2). We examined the effect of muscle glycogen depletion (protocol 1) and the rate of increase in work rate (ramp rate) without muscle glycogen depletion (protocol 2) on S1 and S2. In protocol 1, ten healthy men with a mean age of 31.4 years (S.D. 6.2) were studied on each of 3 days (days 1 and 3 were control days). They performed a ramp exercise test to maximum tolerance and steady‐state tests at rest, during unloaded pedalling and at two constant work rates below their anaerobic threshold (AT). To deplete muscle glycogen before the test on day 2, the subjects performed 2 h of very heavy cycle exercise on the preceding day and fasted overnight. S1 was reduced on day 2 (0.79 compared with 0.95, P less than 0.001), as was the VCO2‐VO2 slope derived from steady‐state measurements (0.81 compared with 0.99, P less than 0.001), but AT and the slope difference (S2 ‐ S1) were unchanged. In protocol 2, seven healthy men with a mean age of 20.6 years (S.D. 2.4) performed ramp tests at three different rates of increasing work rate (15, 30 and 60 W min‐1), each ramp rate being performed twice in random sequence. The ramp rate did not affect S1 but S2 was steeper with the faster rates of work rate increase (1.27, 1.43 and 1.63, respectively, P less than 0.01). Our findings support the concept that the lower component of the V‐slope plot (below AT) represents muscle substrate respiratory quotient (RQ) while the difference between S1 and S2 reflects 'excess CO2' derived from bicarbonate buffering of lactic acid.
Indices for detection of changes in cardiorespiratory fitness during exercise training in man
Authors: Swaine IL , Linden RJ , Mary DA
Published: December 2014

A decrease in the elevation of the linear relation of heart rate on oxygen consumption (HR/VO2) throughout submaximal exercise testing has previously been used in individuals as an index of improvement in cardiorespiratory fitness after a moderate intensity training programme. In the present investigation, changes in HR/VO2 elevation and its variability were quantified and compared with those of other similar indices. These comprised changes in the level of oxygen consumption or heart rate attained at respiratory exchange ratio (R) of unity (VO2/R=1 or HR/R=1. In a first trial in six healthy volunteers, the decrease in HR/VO2 elevation caused by 16 weeks of training significantly exceeded measurement variability, and was associated with increases and decreases respectively in VO2/R=1 and HR/R=1. In a second trial in eight healthy volunteers, the three indices were obtained at four stages during the course of the 16 weeks of training, to grade the improvement in fitness. There were progressive changes in the three indices, the magnitude of which was greatest in the case of the HR/VO2 index. The findings make it possible quantitatively to obtain a graded measure of improvement in fitness during exercise training as indicated by the magnitude of decreases in HR/VO2 elevation.
Muscle and nerve dysfunction in rats with experimental galactosaemia
Authors: Cameron NE , Cotter MA , Robertson S , Cox D
Published: December 2014

The effects of up to 4 months dietary supplementation with 40% galactose on muscle and nerve function were examined in rats. Galactitol, a polyol pathway metabolite, accumulated to high levels in both tissues. This led to changes similar to those found in experimental diabetes, which were largely prevented by treatment with an inhibitor of the first enzyme in the pathway, aldose reductase. For fast twitch extensor digitorum longus muscle there was weight loss, fibre damage, slowing of twitch time to peak, increased twitch tension, and reduced tetanic tension. There were no relaxation deficits. For slow twitch soleus there were no changes in tension production. However, contraction and relaxation for both twitch and tetanus were prolonged. Fatigue resistance was reduced after 1 week. Damage in soleus led to a reduction in mean fibre area after 2 months, which largely recovered by 4 months. There was a selective loss of fast oxidative glycolytic fibres. Histochemical staining for succinic dehydrogenase was normal in galactosaemic soleus, in contrast to the marked reduction seen in diabetes. Sciatic nerve conduction velocity was reduced after 2 months, particularly in normally fast conducting motor and sensory fibres. Resistance to hypoxic conduction block was increased in galactosaemic nerves to diabetic levels. It was concluded that polyol pathway hyperactivity is likely to contribute to the aetiology of diabetic myopathy and neuropathy, and that experimental galactosaemia provides a good model in which to study pathway effects without the complicated hormonal changes found in diabetes.
Liquid flow through monolayers of cultured Madin‐Darby canine kidney cells
Authors: Turner MR
Published: December 2014

The rate of liquid flow per unit area (Jv/A) through Madin‐Darby canine kidney cell monolayers has been studied at temperatures between 0 and 38 degrees C and at transmonolayer hydrostatic pressures between 14 and 44 cmH2O. Jv/A decreased exponentially with time during application of a constant pressure to the free surface of each monolayer. This behaviour resembles the sealing of cultured vascular endothelium. For monolayers sealed between 33–38 degrees C and 30–33 cmH2O, the mean (+/− S.E.M.) half‐time (t1/2) of sealing was 228 (+/− 88) s (n = 6). The decrease in Jv/A during sealing can be expressed as a fraction of the initial Jv/A. Between 33‐38 degrees C and 30–33 cmH2O, the mean (+/− S.E.M.) sealing fraction was 0.58 (+/− 0.06; n = 6). Mean sealing t1/2 was longer at lower temperatures, and longer for glutaraldehyde‐fixed than for unfixed monolayers, but did not vary with transmonolayer pressure. Sealing fraction was not affected by variations in temperature or transmonolayer pressure, or by glutaraldehyde fixation of monolayers. It is argued that sealing is a physical, rather than a biological, phenomenon and that monolayers have non‐linear mechanical properties.
Segmental differences of short‐chain fatty acid transport across guinea‐pig large intestine
Authors: von Engelhardt W , Rechkemmer G
Published: December 2014

Unidirectional fluxes of short‐chain fatty acids (SCFAs) were measured under short‐circuit current conditions across guinea‐pig caecum, proximal and distal colon. Fluxes increased linearly with concentration. In the caecum with equal concentrations on both sides of the mucosa the serosal‐to‐mucosal (sm) fluxes were nearly twice the mucosal‐to‐serosal (ms) fluxes for all SCFAs; in the distal colon ms fluxes were always higher than sm fluxes. Thus, in the caecum the net effect was secretion while in the distal colon net absorption occurred. In caecum, ms fluxes decreased with chain length while sm fluxes were similar for the three fatty acids, acetic, propionic and butyric acid. In the distal colon both unidirectional fluxes increased with chain length. Fluxes across the mucosa of the proximal colon were intermediate to those in caecum and distal colon. A paracellular transport of short‐chain fatty acids is not present. The results indicate that other processes are involved in transcellular transport of SCFA besides non‐ionic diffusion.
Growth‐related change in specific force but not in specific power of rat fast skeletal muscle
Authors: de Haan A , de Ruiter CJ , Lind A , Sargeant AJ
Published: December 2014

The effect of growth on the dynamic performance of rat medial gastrocnemius muscle was studied. From approximately 1.5 to 5 months of age specific force increased by 18%. Reductions were found in both optimal stimulation frequency (from 120 to 100 Hz) and optimal shortening velocity (by 16%) indicating that the fibres became slower. Specific power did not change during growth but was obtained at a lower shortening velocity. Possible mechanisms for the observed changes are discussed.
The effect of [Na+]i and [Na+]o on Ca2+ mobilization in the rat aortic smooth muscle cell line A7r5
Authors: Gillespie JI , Otun H , Greenwell  , Dunlop W
Published: December 2014

Measurements of intracellular calcium (Ca2+i) and sodium (Na+i) have been made in single smooth muscle cells in confluent cultures of the A7r5 cell line using the Ca(2+)‐ and Na(+)‐sensitive dyes Fura‐2 and sodium‐binding benzofuran isophthalate (SBFI). Reversal of the Na+ gradient in control cells results in a small increase in Ca2+i and slows the rate of recovery in Ca2+i following agonist stimulation. This suggests that a Na(+)‐Ca2+ exchange mechanism may be functioning in these cells. In ouabain‐pretreated cells, Na+i is elevated and the recovery from agonist stimulation is significantly slowed. This suggests that the elevation of Na+i alters Ca2+ homeostasis. Reversal of the Na+ gradient in ouabain‐pretreated cells results in a transient increase in Ca2+i which was larger than in control cells. This response is reduced during a second or third exposure to zero Na+o.NA+i, in Na(+)‐loaded cells, falls in the absence of external Na+. This fall is slowed in the absence of external Ca2+ supporting the idea that the Na+ loss is via Na(+)‐Ca2+ exchange. The possible modulation of the Na(+)‐Ca2+ exchanger and Ca2+ mobilization by internal Na+ is discussed.
Is the milk‐fat‐globule membrane a model for mammary secretory cell apical membrane?
Authors: Shennan DB
Published: December 2014

K+(Rb+) uptake by milk‐fat‐globule membrane (MFGM) vesicles and skim‐milk membrane vesicles isolated from bovine milk has been studied. The K+(Rb+) permeability of MFGMs was very low in both high‐ and low‐strength ionic media. In contrast, skim‐milk membranes displayed a significant permeability to K+(Rb+). The results suggest that these membrane preparations do not originate from the same source on the mammary secretory cell and also call into question the suitability of the MFGM as a model for the apical membrane of mammary epithelial cells.