bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions between the leukaemia‐associated ETO homologues of nuclear repressor proteins
Authors: Lindberg Sofia Rondin , Olsson André , Persson Ann‐Maj , Olsson Inge
Published: November 2003

Abstract: The eight‐twenty‐one (ETO) homologues, represented by ETO, myeloid transforming gene‐related protein 1 (MTGR1) and myeloid transforming gene chromosome 16 (MTG16), are nuclear repressor proteins. ETO is part of the fusion protein acute myeloid leukaemia (AML)1‐ETO, resulting from the translocation (8;21). Similarly, MTG16 is disrupted to become part of AML1/MTG16 in t(16;21). The aberrant expression of these chimeras could affect interplay between ETO homologues and contribute to the leukaemogenic process. We investigated possible interactions between the ETO homologues. Ectopic co‐expression in COS‐cells resulted in heterodimerisation of the various ETO homologues suggesting that they may co‐operate. Similarly, the chimeric oncoprotein AML1‐ETO interacted with both MTGR1 and MTG16. However, results from cell lines endogenously expressing more than one ETO homologue did not demonstrate co‐precipitation. Results from IP‐Western and size determination by gel filtration of deletion mutants expressed in COS‐cells, indicated an important role of the HHR domain for oligomerisation. A role was also suggested for the Nervy domain in the homologue interactions. Our results suggest that ETO homologues can interact with each other as well as with AML1‐ETO, although it is unclear as to what extent these interactions occur in vivo.
Preliminary Research on Seed Production and Nutrient Content for Certain Quinoa Varieties in a Saline–Sodic Soil
Authors: Karyotis Th. , Iliadis C. , Noulas Ch. , Mitsibonas Th.
Published: November 2003

The aim of the present study was to compare the potential seed yield of eight quinoa varieties, to explore their mineral composition of seeds and to identify superior varieties in two locations with different soil properties. Compared with neutral soil conditions, seed yield in the marginal (saline–sodic) soil was decreased by 45 %. Under the latter soil conditions seed yield was negatively correlated with crop density, indicating that a considerable yield loss was due to poor and uneven plant density caused by adverse soil properties. Among the varieties, ‘RU–5–PQCIP–DANIDA–UNA’ produced the highest seed yield (>20 dt ha−1) when grown under neutral soil conditions. Under marginal conditions, the above‐mentioned variety and ‘N 407’ produced seed yields up to 10 dt ha−1whereas the rest reached yields of only about 5 dt ha−1. The majority of the varieties accumulated significantly more protein (20 %) in the seeds under saline–sodic soil conditions (lower yielding environment). The varieties originated from South America were superior in accumulating protein in the seeds at both locations. Mineral contents of calcium (Ca), magnesium (Mg), zinc (Zn) and manganese (Mn) in the seeds were significantly higher in the neutral soil. No differences were found for phosphorous (P), iron (Fe), copper (Cu) and boron (B) between the two locations. The South American varieties were again superior in mineral composition. Adaptation of certain quinoa varieties even under marginal environments seems promising for seed production and/or protein and mineral content in the seeds. Agronomic data are needed in a due course, over a higher number of locations and/or various climatic conditions.
Growth and Development of Six Barley (Hordeum vulgare ssp. vulgare L.) Cultivars in Response to a Model Weed (Sinapis alba L.)
Authors: Didon U. M. E. , Boström U.
Published: November 2003

The aim was to study the growth and development of six spring barley (Hordeum vulgare ssp. vulgare L.) cultivars as a response to a model weed population of Sinapis alba L. The development of light interception profiles over time was characterized for each cultivar in weed‐free stands. The cultivars were chosen such that they represent a range of weed‐suppressive abilities based on previously performed trials. One field experiment each was conducted in 1996 and 1997 at a site SE of Uppsala, Sweden. The two cultivars with low competitive ability against weeds, Etna and Blenheim, allowed the highest weed biomass and the lowest crop biomass in competition with the weeds. These two cultivars transmitted more photosynthetic active radiation through the canopy down to 20 and 40 cm height than did the other cultivars. Although the biomass of cv. Etna was low, the grain yield was higher than that of the other cultivars when grown in competition with weeds. In 1997, cv. Svani with good competitive ability against weeds transmitted least light and had greater grain yield than most other cultivars. The absence of a relationship between high grain yield and low weed suppressive ability in the present study indicates that it should be possible for plant breeders to combine high grain yielding capacity with approved weed‐competitive ability.
The Effect of Exposure to Ascending/Descending Imbibition Temperatures in Saline Solutions on Shoot and Root Growth Allocation in Germinating Sorghum Seed
Authors: Kader M. A. , Jutzi S. C.
Published: November 2003

Sorghum (Sorghum bicolor L. Moench) seeds were examined to determine the influence of exposure to ascending and descending imbibition temperature regimes on plumule and radicle axes behaviour of seed after treatment. Treatments included soaking in distilled water, 4.5 % NaCl or 4.5 % KCl for 3 days at three ascending or descending temperatures ranging from 11 to 21 °C. Root growth was enhanced by descending temperatures (21, 16 and 11 °C) over the 3‐day period, whereas ascending temperatures (11, 16 and 21 °C) increased growth differences between shoots and roots. Shoot–root growth was affected by imbibition temperature to a greater extent than germination. However, seed soaking treatments in NaCl or KCl did not improve root or shoot growth, but did improve germination rates.
Maturity Class and P Effects on Soya Bean Grain Yield in the Moist Savanna of West Africa
Authors: Ogoke I. J. , Carsky R. J. , Togun A. O. , Dashiell K. E.
Published: November 2003

Field trials were replicated at four sites in the moist savanna ecological zone of West Africa to study the effect of maturity class and phosphorus (P) rate on grain yield and total protein yield (TPY) of some new soya bean varieties. Grain yield and TPY averaged 1.43 Mg ha−1 and 587 kg ha−1, respectively. Without P application grain yield and TPY were not significantly different among the varieties. In addition, at zero P treatment, grain yield and TPY were not significantly different among three sites where available P was 6.2 mg kg−1 or less. P application depressed grain yield and TPY at a site where the available soil P was high (16.2 mg kg−1). With P application grain yield and TPY were in the range of 1.2–2.28 Mg ha−1 and 505–948 kg ha−1, respectively, for the varieties compared with 0.99–1.12 Mg ha−1 and 454–462 kg ha−1 when P was not applied. The response of grain yield to 30 kg P ha−1 was substantial at Gidan Waya (113 %), Kasuwan Magani (63 %) and Fashola (60 %), three sites where available soil P was low. The application of 30 kg P ha−1 increased grain yield by 21 % in early, 26 % in medium and 58–70 % in the late varieties. Significant variety by P rate interaction effects were observed on grain yield and TPY but not on grain protein concentration (GPC). TPY showed greater response to P in the late varieties than in the early or medium. While seed size correlated significantly and positively with GPC, P application had no significant effect on GPC.
Extracellular distribution of insulin in muscle of rats exposed to long‐term hyperinsulinaemia
Authors: HOLMÄNG A. , LÖNNROTH P. , BJÖRNTORP P.
Published: November 2003

The importance of increased capillary density for the regulation of insulin sensitivity by transcapillary delivery of insulin to muscle cells in insulin‐exposed rats was investigated by direct microdialysis measurements of interstitial [125I]insulin concentrations in the femoral muscle during an euglycaemic hyperinsulinaemic clamp. In insulin‐exposed rats plasma insulin was ∼25% (P<0.05) higher than that in control animals during the first 100 min and reached their maximal concentrations after 100 min. After a nitroprusside infusion given at 100 min both groups had similar concentrations of insulin in plasma as well as in muscle interstitial fluid. However, mean glucose infusion rate during the first clamp hour was 20.5±2.3 and 12.6±5.2 mg kg‐1 min‐1 (P<0.05) in insulin‐exposed and control animals, respectively. During the second clamp hour the corresponding figures were 21.1±2.4 and 13.9±2.6 (P<0.05). It may be concluded that capillarization and/or nitroprusside affected plasma insulin concentrations without altering either the interstitial insulin levels or the insulin effect on glucose consumption. The data suggest that the elevated insulin sensitivity after chronic insulin exposure is dependent on other than transcapillary transport events and demonstrate the different kinetics for insulin distribution in plasma and in the interstitial fluid.
Role of potassium in the regulation of systemic physiological function during exercise
Authors: PATERSON D. J.
Published: November 2003

In exercise, potassium (K+) is released from contracting muscle predominately through K+ channels associated with the repolarization phase of the action potential. Increases in extracellular K+ are directly related to increases in metabolic rate and may reach concentrations as high as 8–9 mm in the arterial blood during exhaustive work. Exercise‐induced hyperkalaemia has been implicated in several physiological processes, in particular skeletal muscle fatigue, hyperaemia, pressor reflex, arterial chemosensitivity and myocardial stability. There is no direct evidence to show that hyperkalaemia causes muscle fatigue, although raised extracellular [K+] may contribute to fatigue during prolonged tetani by depressing the propagation of the action potential down the t‐tubule system, thus impairing the release of Ca2+ from the sarcoplasmic reticulum. The vasodilating properties of K+ may transiently contribute to the early phase of exercise hyperaemia and interact synergistically with other vasoactive substances to cause relaxation by hyperpolarizing K+ channels in vascular smooth muscle. Hyperkalaemia has been implicated in the regulation of arterial blood pressure through activation of the muscle afferent reflex where potassium‐depolarized C fibres may contribute to a reflex increase in arterial blood pressure. K+ can also increase ventilation and the sensitivity of the ventilatory response to hypoxia through direct excitation of the arterial chemoreceptors. Finally, to maintain myocardial electrical stability in exercise, there is a beneficial interaction between raised K+ and catecholamines on the heart, so that when they combine, each offsets the other's deleterious effects.
Na+, K+‐pump activity and skeletal muscle contractile deficits in the spontaneously hypertensive rat
Authors: CARLSEN R. C. , GRAY S. D. , PICKAR J. G.
Published: November 2003

Skeletal muscles in an animal model of genetic hypertension (the spontaneously hypertensive rat, SHR) exhibit significant deficits in contractile performance. These deficits appear to be unrelated to the rise in blood pressure. Slow‐twitch soleus muscles show a decrease in specific muscle tension and a reduced resistance to muscle fatigue during prolonged contractile activity. We tested the hypothesis that the reduced fatigue resistance occurs as a consequence of an impaired ability to maintain or restore Na+ and K+ balance across the sarcolemma during repeated contractions. This may result from a genetically based increase in the Na+ permeability of SHR muscles, coupled with a reduction Na+, K+ pump capacity as the animals mature. Soleus muscles in adult SHR exhibit a significant increase in intracellular Na+ content and a significant decrease in intracellular K+ content at rest. 86Rb+ uptake in Na+‐loaded hypertensive muscles is 45% less than predicted from the number of ouabain‐binding sites available. Activation of Na+, K+ pumps using adrenaline or insulin produces a significantly smaller hyperpolarization in hypertensive soleus than in control muscles. Control soleus muscles are hyperpolarized for at least 10 min after a 4 min period of high‐frequency activity, but hypertensive soleus muscles remain at resting polarity. Nonetheless, the number of ouabain‐binding sites in hypertensive muscles is significantly greater than in control soleus, and binding affinities are similar. This apparent deficit in pump capacity might lead to a greater and more prolonged increase in extracellular K+ during repetitive contractions, and an associated decline in tension. Recently, we have been able to prevent the abnormal decrease in hypertensive soleus fatigue resistance by long‐term treatment (8 weeks) with the Ca2+ blocker amlodipine. The therapy prevented or reversed the contractile deficits, but did not restore the responsiveness of the Na+, K+ pump to hormonal stimulation. The current data suggest that both a reduction in Na+, K+‐pump capacity and changes in Ca2+ distribution play a role in the development of contractile deficits in hypertensive muscles.
Slow recovery of force in single skeletal muscle fibres
Authors: LÄNNERGREN J. , WESTERBLAD H. , BRUTON J. D.
Published: November 2003

After a bout of intense exercise, especially in untrained persons, recovery of muscle force is often slow. Force depression is much more marked at low frequencies of stimulation than at high frequencies (recovery is also seen in single muscle fibres from frog and mouse after fatigue induced by repeated, brief contractions. Evidence from our own and other laboratories indicates that the impairment is unlikely to result from metabolic changes and points to a defect in excitation–contraction coupling. We demonstrate that the likely site of failure is in the coupling between t‐tubule depolarization and release of Ca2+ from the SR. The causative agent appears to be a localized increase in cytoplasmic Ca2+ which initiates some disruptive process, which can, however, be fully reversed, albeit slowly. Our experimental evidence does not support the involvement of Ca2+‐activated proteases. Attempts to clarify the possible role of Ca2+‐activated lipases (phospholipase A2) and Ca2+/calmodulin have been hampered by side‐effects of available inhibitors. Efforts to clarify how Ca2+ exerts its effects are continuing.
Effects of training on potassium, calcium and hydrogen ion regulation in skeletal muscle and blood during exercise
Authors: McKENNA M. J. , HARMER A. R. , FRASER S. F. , LI J. L.
Published: November 2003

Ionic regulation is critical to muscle excitation, contraction and metabolism, and thus for muscle function during exercise. This review focuses on the effects of training upon K+, Ca2+ and H+ ion regulation in muscle and K+ regulation in blood during exercise. Training enhances K+ regulation in muscle and blood and reduces muscular fatiguability. Endurance, sprint and strength training in humans induce an increased muscle Na+, K+ pump concentration, usually associated with a reduced rise in plasma [K+] during exercise. Although impaired muscle Ca2+ regulation plays a vital role in fatigue, little is known about possible training effects. In rat fast‐twitch muscle, overload‐induced hypertrophy and endurance training were associated with reduced sarcoplasmic reticulum Ca2+ uptake, consistent with fast‐to‐slow fibre transition. In human muscle, endurance and strength training had no effect on muscle Ca2+ ATPase concentration. Whilst muscle Ca2+ uptake, release and Ca2+ ATPase activity were depressed by fatigue, no differences were found between strength athletes and untrained individuals. Muscle H+ accumulation may contribute to fatigue during intense exercise and is also modified by sprint training. Sprint training may increase muscle Lac‐ and work output with exhaustive exercise, but the rise in muscle [H+] is unchanged or attenuated, indicating a reduced rise in muscle [H+] relative to work performed. Muscle buffering capacity can be dissociated from this improved H+ regulatory capacity after training. Thus, training enhances muscle and blood K+ and muscle H+ regulation during exercise, consistent with improved muscular performance and reduced fatiguability; however, little is known about training effects on muscle Ca2+ regulation during contraction.
Stimulation of Na+, K+‐pump activity in skeletal muscle by methylxanthines: evidence and proposed mechanisms
Authors: LINDINGER M. I. , WILLMETS R. G. , HAWKE T. J.
Published: November 2003

Evidence is presented to support the hypothesis that submillimolar concentrations of methylxanthines stimulate Na+, K+‐ATPase activity in skeletal muscle. Administration of methylxanthines to skeletal muscle results in plasma membrane hyperpolarization and increased rates of K+ uptake and Na+ efflux. These effects are both dose‐ and time‐dependent and inhibited by blockers of the Na+, K+ ATPase. The mechanisms for stimulation of Na+, K+‐ATPase activity and the signal transduction pathways are not known. The methylxanthine concentrations required for stimulation of Na+, K+‐ATPase activity are less than those required to cause a 50% inhibition of phosphodiesterase activity, and therefore increases in cyclic AMP due to inhibition of the enzyme are not involved. Possible mechanisms by which methylxanthines may increase Na+, K+‐ATPase activity include: (1) a role for increased intracellular [Ca2+]; (2) Ca2+ or adenosine‐receptor‐mediated increases in intracellular cyclic AMP; and (3) a direct action of methylxanthines on the Na+, K+ ATPase.
The Na+, K+ pump in skeletal muscle: quantification, regulation and functional significance
Authors: CLAUSEN T.
Published: November 2003

In skeletal muscle, the Na+, K+ pump is predominantly situated in the sarcolemma (1000–3500 pumps per μm2). The total concentration can be determined in fresh or frozen biopsies (1–5 mg) using a 3H‐ouabain binding assay. The values obtained have been confirmed by measurements of maximum ouabain suppressible Na+, K+‐transport capacity in intact muscles as well as Na+, K+‐ATPase‐related enzyme activity in muscle homogenates. In the mature organism, the concentration of Na+, K+ pumps varies with muscle type and species in the range 150–600 pmol (g wet wt)‐1. In rat and human muscle, the concentration increases markedly with thyroid status. Semi‐starvation and untreated diabetes reduce the concentration by 20–48%. K+ deficiency leads to a downregulation of up to 75%. Both in animals and in humans, training increases the concentration of Na+, K+ pumps in muscle, and inactivity leads to a downregulation.

High‐frequency stimulation elicits up to a 20‐fold increase in the net efflux of Na+ within 10 s This is the major activation mechanism for the Na+, K+ pump, utilizing its entire capacity and possibly represents a drive on de novo synthesis of Na+, K+ pumps. A variety of hormones (insulin, insulin‐like growth factor I, adrenaline, noradrenaline, calcitonin gene‐related peptide, calcitonin, amylin) increase the rate of active Na+, K+ transport by 60–120% within a few minutes. This leads to a decrease in intracellular Na+ and hyperpolarization. In isolated muscles, where contractility is inhibited by high extracellular K+, such agents produce rapid force recovery, which is entirely suppressed by ouabain and closely correlated to the stimulation of K+ uptake and the decline in intracellular Na+. The observations support the conclusion that the Na+, K+ pump plays a central role in the acute recovery and maintenance of excitability during contractile activity.
Fuzzy space and control of Na+, K+‐pump rate in heart and skeletal muscle
Authors: SEMB S. O. , SEJERSTED O. M
Published: November 2003

Since intracellular Na+ activity (aiNa) is one important determinant of Na+, K+‐pump rate as well as excitability and the finely tuned contractility, it is surprising that the relation between aiNa and pump rate reported by different authors has k0.5 varying between 10 and 40 mmol L‐1. Other data also point to a variable relation between pump rate and aiNa. During stimulation of isolated rat soleus muscles at 2 Hz, ouabain‐sensitive 86Rb uptake was increased in spite of the intracellular Na+ remaining unaltered. In isolated cardiomyocytes, a transient Na+, K+‐pump current was observed upon activation by extracellular K+ in spite of good control of aiNa. Na+‐loaded, isolated, sheep cardiac Purkinje fibres initially hyperpolarized over a period of up to 1 min upon activation of the Na+, K+ pump with no detectable change of aiNa. These examples are compatible with the existence of a micro‐environment close to the membrane where diffusion is slower than in the rest of the cytosol, so that local aiNa may fluctuate or gradients may develop as visualized by Wendt‐Gallitelli et al. (1993). We conclude that the reported relationships between Na+, K+‐pump rate and aiNa in intact cells probably underestimate the true affinity of the Na+, K+ pump for Na+ due to a functional diffusion barrier beneath the sarcolemma, and also because of incomplete cell dialysis in whole‐cell voltage clamp experiments. The Na+, K+ pump seems to be preferentially supplied with Na+ from the outside through neighbouring channels and transporters.
Acute effects of C‐peptide on the microvasculature of isolated perfused skeletal muscles and kidneys in rat
Authors: LINDSTRÖM K. , JOHANSSON C. , JOHNSSON E. , HARALDSSON B.
Published: November 2003

The C‐peptide has recently been suggested to have beneficial effects in several organs and improve glycaemic control in human type I diabetes, while there were no such effects in healthy controls. The exact mechanisms behind these effects are, however, not clear. In an attempt to study the actions of C‐peptide on the microvasculature in normal rats during more controlled conditions, isolated rat hindquarters and kidneys were perfused with albumin solutions in order to obtain low basal concentrations of C‐peptide. In rat hindquarters, infusion of C‐peptide significantly increased the capillary filtration coefficients (CFC) from 0.035±0.002 to 0.044±0.002 mL min‐1 100 g‐1 mmHg‐1 (P<0.001, n=9) and the permeability surface area product (PS) for vitamin B12 from 3.48±0.29 to 4.02±0.37 mL min‐1 100 g‐1 (P<0.01, n=6). Addition of C‐peptide to the perfusate during infusion of sodium nitroprusside did not induce any additional alteration of CFC or PS. The vascular resistance was slightly decreased from 2.74±0.17 to 2.64±0.17 mmHg min 100 g mL‐1 (P<0.01, n=9). These effects of C‐peptide are compatible with increases in capillary surface area without alteration of the permeability per se. In isolated rat kidneys perfused at low temperature (8 °C) prepared to inhibit all metabolic processes, C‐peptide induced no changes in glomerular filtration rate, total vascular resistance or fractional albumin clearance. Therefore, C‐peptide causes active vasodilation of the normothermic microvasculature and hence recruitment of capillaries. These findings support the previous observations in man that C‐peptide indeed has biological effects.
Electrophoretic analysis of rat parotid salivary protein composition: investigation of the parasympathetic atropine‐resistant secretion
Authors: EKSTRÖM J. , MARSHALL T. , TOBIN G. , WILLIAMS K. M.
Published: November 2003

Rats pretreated with atropine and adrenoceptor antagonists show secretion of saliva upon electrical stimulation of the parasympathetic nerve of the parotid gland. The protein composition of this secretion has been analysed by sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS–PAGE) and compared with the protein profiles obtained with secretions evoked by parasympathetic stimulation (in the absence of atropine) or infusion of bethanechol with or without vasoactive intestinal peptide (VIP, a probable transmitter conveying parasympathetic secretory impulses). The SDS–PAGE patterns were highly reproducible for an individual rat although minor differences were detected between different rats. The method requires only microlitre volumes of unconcentrated rat saliva and thus is ideal for monitoring sequential aliquots collected from the same rat. The SDS–PAGE patterns indicated (i) little change in the protein profile during prolonged stimulation, (ii) a similar profile with parasympathetic stimulation or infusion of bethanechol, and (iii) a quantitative, rather than qualitative, response to administration of atropine (during parasympathetic stimulation) or VIP (during bethanechol infusion). Thus, the salivary protein composition associated with non‐adrenergic, non‐cholinergic (NANC) secretion appears similar to that evoked in response to parasympathetic nerve stimulation in the absence of muscarinic receptor blockade.
Effect of nitric oxide and renal nerves on renomedullary haemodynamics in SHR and Wistar rats, studied with laser Doppler technique
Authors: BERGSTRÖM G. , RUDENSTAM J. , TAGHIPOUR K. , GÖTHBERG G. , KARLSTRÖ G.
Published: November 2003

The threshold for activation of the humoral renal antihypertensive system, presumably residing in the renomedullary interstitial cells (RIC), is substantially reset upwards in the spontaneously hypertensive rat (SHR). Depressor reactions, normally elicited by an increased renal perfusion pressure, can be inhibited either by high frequency renal nerve stimulation or blockade of nitric oxide synthesis, i.e. manoeuvres decreasing renal blood flow at this high perfusion pressure. The present study was designed to explore the effects on regional renal haemodynamics of blocking NO synthesis with N‐ω‐nitro‐l‐arginine (l‐NNA) in chloralose anaesthetized SHR and Wistar rats. Mean arterial blood pressure (MAP), heart rate (HR), renal blood flow (RBF), cortical blood perfusion (CBP) and papillary blood perfusion (PBP) were measured in renally innervated and denervated SHR (Sin=8, Sdn=8) and in Wistar rats (Win=10, Wdn=10). An innervated non‐treated Wistar group served as control (Cin=12). The laser Doppler technique was used to record CBP and PBP. MAP increased in all groups receiving l‐NNA while HR, RBF and CBP simultaneously decreased. The relative decreases in RBF were more marked into the two SHR groups than in the corresponding Wistar groups. After l‐NNA PBP also decreased in all four groups despite the increased MAP and more so in the Si group; Wi ‐19±8 (P<0.05), Wd ‐17±6 (P=0.07), Si ‐50±9 (P<0.01) and Sd‐25±9% (P<0.05). We conclude that NO is important for maintaining PBP especially in SHR. The more marked decrease in PBP in the innervated SHR suggests a NO/renal nerve interaction in the control of renomedullary blood flow in SHR. This finding may be of importance for the regulation of the humoral renal depressor mechanism.
Effect of changes in transmural pressure on contraction frequency of the isolated right atrium of the rabbit
Authors: BOLTER C. P.
Published: November 2003

Experiments were made on preparations of the rabbit right atrium maintained at 37 °C in oxygenated Krebs–Henseleit solution. Baseline diastolic transmural pressure was held at 2 mmHg. A step increase in diastolic pressure was accompanied by an immediate and rapid increase in atrial rate (fast response), followed by a slower increase (t1/2∼0.5 min) (slow response). The slow response to pressure steps was graded, approaching a maximum increase after a 12 mmHg step (44±4 min‐1 from a baseline of 196±5 min‐1; mean±SEM; n=7; P<0.01). In preparations where baseline atrial rate had been reduced 50% by application of carbamylcholine, the slow response to an increase in pressure was augmented (n=7; P<0.01); an increase of 55±9 min‐1 for a 12 mmHg step in atrial pressure. In preparations where baseline rate had been increased 63% by the application of isoprenaline, the slow response was attenuated (n=5, P< 0.01), an increase of 22±7 min‐1 for a 12 mmHg step. During sinusoidal pressure forcing (0.002–1.0 Hz), rate responses of control and carbamylcholine‐treated preparations had a high gain at frequencies 0.02 Hz. Carbamylcholine‐treated preparations also showed a high gain at frequencies 0.2 Hz. There appear to be two distinct intrinsic responses to changes in right atrial pressure; a rapid response which is augmented by cholinergic stimulation, and a slower response which is augmented by cholinergic stimulation and reduced by β‐adrenergic stimulation.
Effects of hCGRP 8‐37 and the NK1‐receptor antagonist SR 140.333 on capsaicin‐evoked vasodilation in the pig nasal mucosa in vivo
Authors: RINDER J. , LUNDBERG J. M.
Published: November 2003

A novel pig in vivo model was used to study vascular effects of capsaicin, substance P and calcitonin gene‐related peptide (CGRP) in the nasal mucosa and skin. An acoustic rhinometer was used to measure changes in nasal cavity volume, mainly representing changes in capacitance vessels in the vascular beds. The non‐peptide NK1‐receptor antagonist SR 140.333 and the CGRP‐receptor antagonist hCGRP 8‐37 were used to investigate the role of substance P and CGRP, respectively, in capsaicin‐evoked vasodilation mediated through activation of sensory C‐fibre afferents. In this study we show that SR 140.333 is a potent inhibitor of substance P‐induced vasodilation in the nasal mucosa whereas it has no effect on the capsaicin‐evoked responses. Substance P only elicited a minor and shortlasting increase in superficial skin blood flow; this response, however, was completely blocked after administration of SR 140.333. Capsaicin‐evoked vasodilation in the skin was slightly reduced by SR 140.333. CGRP‐induced vasodilation in the nasal mucosa and skin was of much longer duration than the substance P‐induced response, and was thus similar to the vascular effects mediated by capsaicin. hCGRP 8‐37 significantly reduced both the CGRP‐ and capsaicin‐mediated vasodilation in the nasal mucosa and the decrease of nasal cavity volume. Although the peak vasodilation in the skin in response to capsaicin, was unaltered by blockade of CGRP‐receptors, the integrated response was significantly reduced by hCGRP 8‐37. The present results show that vasodilatory responses to activation of afferent nerves in the pig nasal mucosa and superficial skin are mainly dependent on CGRP, while NK1‐receptor mechanisms seem to be of no or minor importance.
Impaired glomerular permselectivity for albumin in chemically medullectomized WKY rats
Authors: BERGSTRÖM G. , JOHNSSON E. , LINDSTRÖM K. , RUDENSTAM J. , HARALDSSON B.
Published: November 2003

Chemical renal medullectomy with 2‐bromo‐ethylamine hydrobromide (BEA) has been used to study the importance of the renal medulla in blood pressure regulation. However, conclusive evidence as to whether BEA treatment affects the glomerular barrier is lacking. In the present study, the effects of BEA upon glomerular permselectivity for albumin were studied using isolated kidneys (IPK) perfused at a low temperature (8 °C) to inhibit tubular reabsorption of proteins. Sixteen WKY rats (WB) received an i.v. injection of BEA (150 mg kg‐1) while 10 rats served as controls (WC). Volume balance, urinary osmolality and creatinine clearance (GFR) were measured in metabolic cages. Acute paired experiments (n=9) were performed 5–7 weeks after BEA. The rats were anaesthetized and the total in vivo albumin excretion was recorded. The kidneys were then isolated and perfused for measurements of inulin clearance (GFR) and fractional albumin clearance without tubular reabsorption of protein. The nine BEA treated rats showed polyuria and hypoosmotic urine. In vivo GFR was lower in the BEA treated groups when measured with creatinine clearance (459±22 vs. 213±41 μL min‐1 100 g‐1 body wt, P<0.001), while GFR was not significantly changed in the IPK (WC=135±27, WB=92±14 μL min‐1 100 g‐1 body wt, n.s.) when perfused at identical pressures. The fractional albumin clearance was increased three times in the BEA group (WB=9.6±3.4J, P<0.05). Moreover, albumin excretion in vivo was similar in the two groups despite low GFR in the BEA group. We conclude that BEA treatment affects glomerular permselectivity for albumin.
Specificity of training velocity and training load on gains in isokinetic knee joint strength
Authors: AAGAARD P. , SIMONSEN E. B. , TROLLE M. , BANGSBO J. , KLAUSEN K.
Published: November 2003

The present study investigated the effects of three different strength training regimes on the isokinetic strength profile of the knee extensors (quadriceps, Q) and flexors (hamstrings, H) and if increases in isokinetic strength were accompanied by an enhanced performance during a more complex leg movement, the soccer kick. Twenty‐two elite soccer players performed 12 weeks of strength training (three times per week) at either high resistance (HR group: 4 sets, 8 reps, 8RM loading), low resistance (LR group: 4 sets, 24 reps, 24RM loading), loaded kicking movements (LK group: 4 sets, 16 reps, 16RM loading) while one group served as controls (CO group). Isokinetic concentric and eccentric moment of force was obtained (KinCom) as peak moment (Mpeak) and moment at 50° knee flexion (M50) at angular velocities of 30, 120, 240° s‐1. Isokinetic knee joint strength was unchanged in groups LR, LK, CO. However, after the HR strength training, concentric Mpeak (±SD) increased (P<0.01) at 30° s‐1 (Q, 258±37 to 297±57 Nm; H, 122±22 to 140±21 Nm). Furthermore, eccentric Mpeak increased at 30, 120 and 240° s‐1 (Q, 274±60 to 345±57 Nm (P<0.01), 291±56 to 309±49 Nm and 275±43 to 293±36 Nm (P<0.05), respectively; H, 143±32 to 158±25 Nm, 152±39 to 169±31 Nm and 148±27 to 163±19 Nm (P<0.05)). Corresponding increases (P<0.05) were observed for M50. The H/Q ratio calculated as eccentric hamstring strength divided by concentric quadriceps strength (Hecc/Qcon, representative for knee extension) at 240° s‐1 increased (P<0.05) from 107 to 118% (based on Mpeak) and from 90 to 105% (M50). Kicking performance estimated by maximal ball flight velocity was unaffected by any of the strength training regimes investigated. In conclusion, only heavy‐resistance strength training induced increases in isokinetic muscle strength in the absence of learning effects. Concentric strength gains were observed at the actual velocity of training, while eccentric strength gains were found over the entire range of velocities examined. The capacity of the hamstring muscles for providing stability to the knee joint during fast extension was augmented as a result of the heavy‐resistance strength training. Strength training should be integrated with other types of training involving the actual movement pattern in order to increase the performance within more complex movement patterns.
A comparison of the effects of two antispastic drugs, tizanidine and baclofen, on synaptic transmission from muscle spindle afferents to spinal interneurones in cats
Authors: SKOOG B.
Published: November 2003

The α2‐adrenergic agonist tizanidine was reported to be more efficient than baclofen in reducing muscle tone in some spastic patients. The aim of this study was to investigate if this might be due to more specific depressive actions of tizanidine on transmission from muscle afferents which contribute to muscle tone. This was done by comparing the effects of tizanidine and baclofen on amplitudes of monosynaptic spinal focal field potentials produced by stimulation of muscle nerves in the cat. Such field potentials were recorded in the intermediate zone of the fourth lumbar segment, where they display two distinct components, an early one from group I afferents and a later one from group II afferents. Both reflect EPSPs produced in interneurones in disynaptic pathways to motoneurones. Tizanidine strongly depressed potentials caused by group II afferents, while it had no effect or slightly facilitated potentials produced by group I afferents. In contrast, baclofen had inconsistent effects on the group II potentials; in some cases it caused a depression and in others it caused only an increase in the latency and time to peak, at doses that strongly and consistently depressed the group I potentials. These effects have been found after both local and systemic applications. The antispastic actions of tizanidine may therefore only be related to the depression of transmission from group II muscle afferents, while antispastic actions of baclofen may be secondary to the depression of any sensory fibres. Since tizanidine is as effective in depressing spasticity as baclofen, it is suggested that the enhancement in synaptic transmission from group II muscle afferents may play an important role in the development of exaggerated stretch reflexes in spastic patients.
Restoration of cardiac contraction by angiotensin II during raised [K+]o in the rabbit
Authors: RYAN D. M. , PATERSON D. J.
Published: November 2003

Catecholamines restore cardiac contraction depressed by hyperkalaemia (raised [K+]o) and acidosis, yet in exercise hyperkalaemia and acidosis are tolerated during βadrenergic blockade. To test whether the negative effects of raised [K+]o are offset by a non‐adrenergic hormone, angiotensin II (AII) was given to rabbit papillary muscle (AII 75 nm, n=9) and rabbit isolated working hearts (AII 5 nm, n=8) perfused with 8 and 10 mm K+ Tyrode at 37 °C. A similar protocol was also performed in a further nine isolated hearts treated with propranolol (1 μm) and prazosin (1 μm). AII caused a significant (P<0.01) increases in contraction and aortic flow in normal Tyrode and maintained aortic flow during high [K+]o. In the papillary muscle and isolated heart treated with adrenergic blockers, high [K+]o reduced the stimulatory effects of AII, but contraction and aortic flow was still significantly greater (P<0.01) than in high [K+]o alone. These results show that AII can ameliorate the depressive effects of high [K+]o on the heart. The local release of AII in the heart during activation of the sympathetic nervous system and the rise in circulating AII during exercise could therefore play a role in protecting the heart from hyperkalaemia.
Oleic acid binding and transport capacity of human red cell membrane
Authors: BOJESEN I. N. , BOJESEN E.
Published: November 2003

Resealed human red cell membranes, ghosts, bind oleate (OL) by a limited number of sites when equilibrated at 37 °C, pH 7.3 with OL bound to bovine serum albumin (BSA) in molar ratios below 1.5. The binding capacity is 34±2.2 nmol g‐1 ghosts with a dissociation equilibrium constant (37 °C) Kdm 1.38±0.15 fold Kd of albumin binding. Kdm is temperature independent and ∼7–8 nm.

Exchange efflux kinetics at 0 °C to buffers of various albumin concentrations ([BSAy]) is biexponential and is analysed in terms of a three‐compartment model. Accordingly the ratio of inner to outer membrane leaflet binding sites is 0.450±0.018 and the rate constant of unidirectional flux from inside to outside is 0.067±0.01 s‐1. The rate constant of flux from the extracellular side of the membrane to BSAy increases with the square root of [BSAy] as expected of an unstirred layer effect. This provides an estimate of the dissociation rate constant of OL–BSA complex at 0 °C of 0.0063±0.0003 s‐1.

Exchange efflux from ghosts containing four different [BSAi] obeys the expected kinetics of a three‐compartment approximation of the theoretical model. Accounting for the effect of an unstirred fluid inside ghosts, the rate coefficients fit the values predicted by the parameters obtained by the studies of albumin‐free ghosts. The results show that the OL transport across the membrane is mediated exclusively by the asymmetrically distributed binding sites. The differences between transport sites of three long‐chain fatty acids suggest that they are protein determined microdomains of phospholipids.
Tachykinins increase vascular permeability in the gastrointestinal tract of the rat
Authors: LÖRDAL M. , HÄLLGREN A. , NYLANDER O. , HELLSTRÖM P. M.
Published: November 2003

The occurrence of inflammation as indicated by extravasation of Evans blue bound to plasma proteins was examined in various parts of the gastrointestinal tract in the rat, following administration of tachykinins, capsaicin and hydrochloric acid. Intravenous neurokinin A dose‐dependently induced extravasation in stomach, duodenum, jejunum, caecum and colon, but had no effect in ileum. Neurokinin B equipotently induced extravasation in the stomach but had no effect in other parts of the gut and substance P had no effects on extravasation of Evans blue in any of the examined parts of the gastrointestinal tract. Capsaicin given intraperitoneally increased vascular permeability in stomach and duodenum only, while extravasation of Evans blue after capsaicin given intraluminally did not differ from the effect of the vehicle alone. As a comparison, HCl given intraluminally in the duodenum was found to induce a prominent extravasation of Evans blue of a greater magnitude than that of tachykinins. We suggest that tachykinins, and in particular neurokinin A, may be of importance for extravasation of plasma proteins as part of inflammatory reactions in the upper and lower gastrointestinal tract.
Proximal tubular lithium/plasma concentration ratio depends on tubular fluid flow rate
Authors: LEYSSAC P. P. , CHRISTENSEN P.
Published: November 2003

Previous studies have given slightly different values of proximal tubular fluid/plasma lithium concentration ratios (TF/P)Li. The aim of the present study was to investigate whether the technique of tubular fluid collection by micropuncture might contribute to this difference. Early distal and late proximal tubular fluid was collected by micropuncture during recording of early proximal hydrostatic pressure with varying pressures applied to the collection pipette. Distal fluid collection with 2–3 mmHg suction was unable to influence distal flow, proximal tubular pressure, nephron filtration rate (SNGFR), (TF/P)Li or (TF/P)Na significantly, as compared with values obtained without suction. In contrast, during late proximal collections, tubular pressure could be controlled. Within the range 2 mmHg below to 6 mmHg above free flow pressure maintained during collection, proximal flow rate varied from 9 to 44 nL min‐1. (TF/P)Li was positively and significantly correlated to late proximal flow rate (P<0.005, r=0.65), independent of tubular pressure. (TF/P)Na was 1.03 and independent of flow rate and pressure. With collection adjusted to a late proximal flow of 24 nL min‐1, (TF/P)Li would be about 1.15. At the more physiological flow rate of 12–14 nL min‐1, (TF/P)Li was not significantly different from 1.00. It is concluded that proximal Li transport is distinct from Na transport and lags behind Na and water transfer only when flow rate is increased above normal. The result emphasizes the importance of the micropuncture fluid collection technique for estimates of proximal (TF/P)Li.
Effects of strength and endurance training on isometric muscle strength and walking speed in elderly women
Authors: SIPILÄ S. , MULTANEN J. , KALLINEN M. , ERA P. , SUOMINEN H.
Published: November 2003

The separate effects of 18 weeks of intensive strength and endurance training on isometric knee extension (KE) and flexion (KF) strength and walking speed were studied in 76‐to 78‐year‐old women. Maximal voluntary isometric force for both KE and KF was measured in a sitting position on a custom‐made dynamometer chair at a knee angle of 60° from full extension. Maximal walking speed was measured over a distance of 10 m. The endurance‐trained women increased KE torque and KE torque/body mass after the first 9 weeks of training when compared with the controls. When comparing the baseline, 9 week and 18 week measurements within the groups separately, both the endurance‐ and strength‐training groups increased KE torque, KE torque/body mass and walking speed. Individual changes in KE torque/body mass before and after 18 weeks of training averaged 19.1% in the strength group, 30.9% in the endurance group and 2.0% in the controls. This study indicates that in elderly women the effects of physical training on muscle strength and walking speed occur after endurance as well as strength training. The considerable interindividual variation in change of muscle performance is also worth noticing.
Effects of preceding movements and contractions on the tonic vibration reflex of human finger extensor muscles
Authors: NORDIN M. , HAGBARTH K.‐E.
Published: November 2003

The vibration sensitivity of feline muscle spindle endings is known to vary as a result of preceding muscle conditioning manoeuvres. If similar after‐effects occur in man they should be expected to influence the strength of the tonic vibration reflex (TVR). To study this issue, vibration was applied over the finger extensor tendons of 11 volunteers who actively held their fingers in a semi‐extended position. The TVR, measured as electromyographic responses and angular deflections at the metacarpophalangeal joints, was found to be stronger when the extensors prior to the test had been contracted in a shortened position than when they had been contracted in a stretched position. This difference was reduced when the vibration stimulus was preceded by a strong extensor contraction in the test position. The antigravity extensor EMG activity required to keep the fingers in the test position was weaker when the conditioning contraction was performed at a short muscle length than when it was performed at a long muscle length. The variations in magnitude of the TVR can be attributed to ‘thixotropic’ properties of intrafusal muscle fibres, resulting in a slack following conditioning at a long muscle length. The different EMG levels required for position holding can be explained by similar properties of extrafusal muscle fibres. In conclusion, the results demonstrate the importance of taking the ‘history of movement’ into account in the design of all TVR studies.
Reversible depression of action potentials and force production in frog single muscle fibres by calmodulin‐inhibitors
Authors: BRUTON J. D. , WESTERBLAD H. , LÄNNERGREN J.
Published: November 2003

The effects of the calmodulin‐inhibitors trifluoperazine, thioridazine and zaldaride maleate on the responses to electrical stimulation in isolated frog skeletal muscle fibres were investigated. All three drugs initially reduced the amplitude of the action potentials but potentiated twitch force. This was followed by a total loss of action potentials and force production. However, the resting membrane potential was not changed. The effects were completely reversible upon removal of the drugs. These results suggest that an intact calmodulin system is required for normal function of the sarcolemmal sodium channels of frog skeletal muscle.
Effect of increased interstitial fluid flux on fractional catabolic rate of high molecular weight [3H]hyaluronan injected in rabbit skin
Authors: REED R. K. , LAURENT U. B. G. , KING S. , FRASER J. R. E. , LAURENT T. C.
Published: November 2003

The removal rate of high molecular weight (Mr 3×106) [3H]hyaluronan has been measured in rabbit paw skin in control and during increased local venous pressure induced by ligation of the femoral vein. The increased venous pressure resulted in a 20% increase of interstitial volume at 4 h after ligation, a value which relates to at least a doubling of lymph flow, i.e. also to doubling of fluid flux through the tissues. The fractional catabolic rate of hyaluronan was 0.0918±0.0170 h‐1 (n=10) and 0.0775±0.0206 h‐1 (n=11) in control and following increased venous pressure respectively (P>0.05). Since the fractional catabolic rate of hyaluronan is not affected by increased venous pressure, the removal of hyaluronan via lymphatic drainage in rabbit paw skin must be small compared to the local turnover of the polysaccharide.