bluuebunny/crossref_metadata_2025 huggingface dataset:
Synchronization of Activity in Afferent Nerve Branches within the Frog's Muscle Spindle
Authors: Ottoson D. , Shepherd G. M.
Published: December 2008

The mechanisms underlying the generation of activity in the afferent nerve branches within the muscle spindle have been studied in isolated frog spindles. Repetitive stimulation at given frequencies and strengths caused a disintegration of the synchronous activity of the spindle as revealed by a decomposition of the impulse into small abortive spikes of different amplitudes. The breakdown of synchronous activity was preceded by a stage during which the impulse appeared gradually later but then remained steady at a given delay. The isolated receptor potential exhibited a latency shift closely similar to that of the impulse response under repetitive stimulation. Treatment of the spindle with tetrodotoxin at critical concentrations caused a decomposition of the impulse similar to that with repetitive stimulation. It could be shown in these spindles that synchronization of the activity within the spindle is related to the amount of depolarization of the sensory endings. The mechanisms for generation of activity in the spindle are discussed in relation to the structural organization of the branches of the afferent fibre. It is concluded that the anatomical and functional properties of the spindle provide the basis for a synchronization of the activity of its different parts during the response to an applied stretch.
Regional Differences in the Incorporation Rates of 3H‐Acetate and 35S‐Sulfate into Chondroitin Sulfate of Mouse Costal Cartilage in Vitro
Authors: Herbai Georg , Lindahl Ulf
Published: December 2008

The rates of incorporation of 3H‐acetate and 35S‐sulfate into chondroitin sulfate of mouse costal cartilage were studied by an in vitro‐incubation technique. Cartilage specimens from two different regions of costal cartilage prepared from growing mice, were incubated for varying periods of time. Chondroitin sulfate was isolated, after proteolytic digestion of the tissues, by repeated precipitation with cetylpyridinium chloride. The average incorporation rates, which were followed during 24 hrs, showed a marked decrease after 2 hrs of incubation and then remeained essentially constant. During the entire incubation period much more exogenous sulfate than acetate was incorporated into the segments. Considerably more exogenous sulfate and acetate were incorporated into the lateral segments of the cartilage, including the osteochondral junctions, than into the medial segments. It is concluded that chondroitin sulfate is synthetized at a higher rate in the vicinity of the osteochondral junction than in other portions of mouse costal cartilage.
Studies on the Mechanism of Action of Lithium Ions
Authors: Giacobini E. , Hovmark S. , Stepita‐Klauco M.
Published: December 2008

The complete replacement of the extracellular Na+ by lithium (Li+) (in 7.8 mM K+ medium) leads to an accumulation of Li+, and a simultaneous decrease in Na+ and K+ in the stretch receptor neuron. Li+ replacement in a medium with a lower K+ concentration (2.4 mM) decreases the quantities of both K+ and Li+. The possibility of a K+ sensitive carrier transporting Li+ into the cell is suggested.
Regional Distribution of Red Cells, Plasma and Blood Volume in the Intestinal Wall of the Cat
Authors: Jodal Mats , Lundgren Ove
Published: December 2008

The distribution of red cells, plasma and blood volume in the wall of the small intestine and in the colon was determined by means of 51Cr‐labelled red cells and 125I‐labelled serum albumin. It was demonstrated that the submucosal tissue layer was the most vascularized. Assuming a total blood content in the intestinal and colonic wall of 5 ml blood/100 g tissue, the regional blood content in the submucosa could be calculated to 10–20 ml/100 g tissue, while the blood content of the mucosa and muscularis amounted to approximately 3 ml/100 g.
Ventilatory Responses to Hypoxia and Hypercapnia with External Airway Resistance
Authors: Barnett Thomas B. , Rasmussen Birger
Published: December 2008

The effects of added external airway resistance upon the steady state ventilatory response to hypoxia and hypercapnia were studied in three normal human subjects. The slope of the stimulus‐response line for CO2 was reduced in all subjects when this resistance was added to the airway. The ventilatory response to eucapnic hypoxia was measured in the same subjects with and without the same added external airway resistance. When end‐tidal carbon dioxide tension was maintained at the normal level by addition of CO2 to the inspired air, the ventilatory response to hypoxia was less in all subjects with added airway resistance than without. For purposes of comparison the level of hypoxia and of hypercapnia that were associated with hyper‐ventilation of 12 1/min were considered to be physiologically equivalent stimuli. At this stimulus level the magnitude of the effect of the same added airway resistance was greater in all subjects during hypercapnia than during hypoxia. These observations suggest that the ventilatory response to hypoxia is less dependent upon the resistive work of breathing than is the response to hypercapnia.
Discharge Patterns in Human Muscle Spindle Afferents during Isometric Voluntary Contractions
Authors: Vallbo Å. B.
Published: December 2008

Unitary nerve impulses were recorded from the median nerve of waking human subjects with percutaneously inserted tungsten electrodes. Activities from 63 muscle spindle endings were studied during isometric voluntary contractions. Three main types of response patterns were encountered: a sustained increase of the discharge, a sustained decrease, and a weak discharge consisting of a few impulses. It was concluded that the sustained increase of the discharge was accounted for by an increase of the fusimotor activity, whereas the sustained decrease was accounted for by mechanical unloading. The weak discharge might be accounted for by either mechanical or fusimotor mechanisms. Fusimotor activation concomitant with the skeletomotor activity could be demonstrated for 81% of the spindle afferents. One particular response pattern was not characteristic for certain endings but many units responded with different patterns depending upon the intensity and spatial extent of the contraction. Analyses of the unitary responses to the contraction of different muscle portions indicated that there was a close spatial correspondence in the muscle between the skeletomotor activity and the fusimotor activity.
Metabolic Effects of Prolonged Sympathetic Nerve Stimulation in Canine Subcutaneous Adipose Tissue
Authors: Fredholm Bertil B. , Karlsson Jan
Published: December 2008

The release of glycerol, free fatty acids (FFA), lactate, pyruvate and CO2as well as the uptake of glucose and O2was investigated in canine subcutaneous adipose tissue perfused with blood at a constant rate. Biopsy specimens were analyzed for lactate and glycogen content. Water was found to constitute 17±4 per cent of the wet weight. In unstimulated adipose tissue net glycerol release was 0.25±0.03 and net FFA release 0.12±0.06 μmoles/min/100 g adipose tissue. Both increased during sympathetic nerve stimulation for 50 min. The release of FFA and glycerol was enhanced by inhibition of adrenergic α‐receptors (dihydroergotamine 75–150 μg i.a.) and abolished by blockade of adrenergic β‐receptors (propranolol 400 μg i.a.). Basal glucose uptake averaged 1.4 μmoles/min/100 g tissue and was not significantly affected by nerve stimulation either before or after receptor blockade. The glycogen content, which averaged 3 μmoles glucose/g tissue during basal conditions, decreased by 30 per cent during sympathetic nerve stimulation, provided β‐receptors were not inhibited. During nerve stimulation lactate accumulated in adipose tissue and there was an increased net release of lactate into the blood. These effects were inhibited by either α‐ or β‐receptor blockade. During basal conditions 2.4±0.6 μmoles O2were extracted per min per 100 g tissue. The extraction decreased upon nerve stimulation provided α‐receptors were intact and increased if they were inhibited.

The results indicate that stimulation of adrenergic β‐receptors in adipose tissue causes lipolysis and glycogenolysis and that this mobilization when combined with α‐adrenergic vasoconstriction leads to increased production and accumulation of lactate.
Adrenocorticoid regulation of Na+, K+‐ATPase in adult rat kidney: effects on post‐translational processing and mRNA abundance
Authors: CELSI G. , STÅHL J. , WANG Z. ‐M. , NISHI A.
Published: December 2008

The mechanisms by which adreno‐corticoid hormones regulate Na+, K+‐ATPase in adult kidney were studied in adrenalectomized (Adx) rats. Five days after adrenalectomy, Na+, K+‐ATPase activity was significantly reduced in the renal cortex homogenate (C = 13.0±0.8 vs. Adx = 7.1±0.7 μmol Pi mg‐1 protein h‐1) and in renal microsomes (C = 30.3 ± 1.9 vs Adx = 14.6 ± 1.3 μmol Pi mg‐1 protein h‐1). Glucocorticoid replacement treatment of adrenalectomized rats with betamethasone (20 μg kg‐1 body wt twice daily for 5 days) effectively counteracted the observed reduction in Na+, K+‐ATPase activity. In cortical homogenate the protein level of α1 and β1 subunits measured in immunoblots was not significantly different in Adx and control rats, indicating that 5 days after adrenalectomy the α1 and β1 subunits were present in renal cortical cells to almost normal extent but could not be assembled into a transmembrane functional unit. In support of this conclusion we found that the protein level of both the α1 and β1 subunits was significantly lower (P < 0.001 for both subunits) in microsomes from Adx than in control rats. The mRNA abundance for α1 and β1 subunits were not lower in Adx as compared to control rats 1 and 5 days after surgery. However, if Adx rats were given a single dose of betamethasone (600 μg kg‐1 body wt), a significant 2‐fold increase in both α1 and β1 mRNAs was observed (P < 0.05 for both subunits).

These data suggest that glucocorticoids can upregulate the mRNA of both Na+, K+‐ATPase subunits but that the low renal Na+, K+‐ATPase activity in adult Adx rats is mainly due to loss of glucocorticoid regulation of the post‐translational processing of the enzyme.
Postural changes in atrial natriuretic peptide (ANP) and fluid balance in conscious goats
Authors: KOKKONEN U.‐M.
Published: December 2008

To gain insight into how weak physiological stimuli suffice to release ANP, the effects of 15° head‐up and head‐down tilt, 90 min each in succession, on plasma atrial natriuretic peptide (ANP), plasma cortisol, plasma and urinary Na, K and osmolality, plasma proteins and haematocrit were studied in five conscious goats before and after 2 wk daily training for the tilting procedure.

In the trained goats the 15° tilt did not affect the plasma ANP, cortisol or the urine excretion significantly. Total plasma proteins decreased significantly. In the untrained goats, on the other hand, an increasing trend was observed in the plasma ANP and cortisol as well as in the urine Na excretion during the head‐up tilt. During the head‐down tilt, the levels of ANP and Na excretion remained elevated. The plasma ANP was significantly increased after 40 min, by 28% as compared to the pre‐tilting level. The plasma cortisol was first elevated, but then returned to the starting level. The results suggest that in the trained goats the responses to tilting were unmasked. Despite minor effects of the 15° tilt in itself, increased plasma ANP seemed to be associated with increased natriuresis.
Is the mean power frequency shift of the EMG a selective indicator of fatigue of the fast twitch motor units?
Authors: GERDLE B. , FUGL‐MEYER A. R.
Published: December 2008

During repeated maximum isokinetic contractions parallel decreases in output and the mean power frequency (MPF) of the electromyogram (EMG) occur, followed by stable levels (the endurance level). This study aimed to investigate if hypoxia of the plantar flexors will result in a shift in MPF during the endurance level.

Mechanical performance and simultaneous surface EMG activity of three plantar flexors (m. soleus, m. gastrocnemius medialis and m. gastrocnemius lateralis) were recorded during repeated isokinetic plantar flexions at 1.05 rad s‐1 in 10 healthy women. The study consisted of two tests with 14 days in between:

(1) a maximum test consisting of 125 maximum plantar flexions. After 100 contractions, using a tourniquet, a relative ischaemia (hypoxia) was induced.

(2) a submaximum test performed at the level established between contractions 70–100 of the maximum test, consisting of 125 plantar flexions.

During the maximum test mechanical performance output, the signal amplitude (RMS) of the EMG and the MPF decreased in parallel during the initial 50 contractions followed by stable levels during the subsequent 50 contractions. When hypoxia was induced decreases in mechanical performance and RMS appeared without significant decreases in MPF.

The present study indicates that the MPF shift is mainly sensitive to biochemical changes in the type 2 fibres. Hypoxia mainly located to the type 1 fibres will not be detected using the MPF variable.
Differential responses in post‐ and pre‐ganglionic adrenal sympathetic nerve activity and renal sympathetic nerve activity after injection of 2‐deoxy‐d‐glucose and insulin in rats
Authors: CARLSSON S. , SKARPHEDINSSON J. O. , DELLE M. , HOFFMAN P. , THORÉN P.
Published: December 2008

The aim of the study was to compare pre‐ganglionic adrenal nerve activity (pre‐aSNA) to post‐ganglionic adrenal nerve activity (post‐aSNA) in rats after administration of 2‐deoxy‐d‐glucose (2‐DG, 500 mg kg‐1, i.v.), which mimicks a central hypoglycaemia or to the response in pre‐aSNA and post‐aSNA to hypoglycaemia after injection of insulin (5U). Renal postganglionic sympathetic nerve recordings (rSNA) in a separate group was used as a reference.

Adrenal or renal multifibre nerve activity was recorded in chloralose‐anaesthetized Wistar‐rats. Trimethaphan, a short‐lasting ganglionic blocker, was administered i.v. (10 mg kg‐1) in order to test for pre‐ or post‐aSNA in the adrenal nerves. The adrenal nerves was considered to contain predominantly post or preganglionic fibres, respectively if the nerve activity in the adrenal nerve decreased (post‐aSNA) or increased (pre‐aSNA). In contrast, all renal nerves showed almost a pure postganglionic activity.

Post‐aSNA responded with a tendency to increase after the 2‐DG injection. The highest value (percentage change from control) 5 min after injection was 12 ± 9%. The pre‐aSNA increased with values of 99 ± 52% at 3 min and 86 ± 31% at 5 min (percentage change from control). The activity in the rSNA was only slightly decreased after the injection of 2‐DG when compared to pre‐drug control activity. There was a significant difference between the pre‐aSNA vs. post‐aSNA at 1 min (P < 0.05), 3 min (P < 0.01) and 5 min (P < 0.05).

Insulin caused an increase in post‐aSNA with the maximum level of 154 ± 8% reached at 40 min compared to pre‐aSNA, which increased substantially and reached a peak value of 349 ± 43% at 50 min. RSNA was also increased with a maximum level, 160 ± 29% at 50 min (P < 0.01). There was a significant difference in the main effect in pre‐aSNA vs. post‐aSNA.

Thus, this study gives further evidence that the adrenal gland is innervated by both post‐ and pre‐ganglionic fibres with different characteristics.
The 1991 Ulf von Euler Lecture:Thel‐arginine: nitric oxide pathway
Authors: MONCADA S.
Published: December 2008

‘We must always guard the liberties of the mind and remember that some degree of heresy is often a sign of health in spiritual life.’ U. S. von Euler,Circulation,26(1962), 1233.
Renal response to volume depletion and expansion in Milan hypertensive rats
Authors: BOBERG U. , MORSING P. , PERSSON A. E. G.
Published: December 2008

In previous studies on Milan hypertensive (MHS) rats, we found an impaired tubuloglomerular feedback (TGF) response before, during and after development of hypertension. In the present study MHS rats and rats of the Milan normotensive strain (MNS) were investigated after 24 hours of volume depletion (VD) and subsequently after 5% isotonic volume expansion (VE) with respect to whole kidney function, interstitial hydrostatic (Pint) and oncotic (IIint) pressures, stop‐flow pressure characteristics of TGF and changes in early proximal flow rate in response to increased loop of Henle flow. MHS rats had higher mean arterial blood pressure (Pa) than MNS rats (129 vs. 101 mmHg) both after VD and after subsequent VE. No difference in glomerular filtration rate (GFR) was found. Both strains had a low urine flow rate (1.5 μl min‐1) during VD, which increased fourfold after VE. The interstitium was significantly more dehydrated in MHS, as indicated by a more negative net interstitial pressure (Pint–±int t than in MNS (‐1.3 ± 0.3 vs. ± 0.0 ± 0.5 mmHg) after VE. The TGF mechanism was more activated in MHS during volume depletion, as indicated by a larger drop in stop‐flow pressure (Psf) in response to loop of Henle perfusion (7.1 ± 0.7 vs. 4.7 ± 0.2 mmHg, P < 0.05). However, during VD the loop of Henle flow that elicited half maximal response in Psf, the turning point (TP), was equally low in MHS and MNS (13.5 ± 0.6 and 14.3 ± 0.4, respectively). After VE, however, TP increased significantly more in MNS to (32.6 ± 2.1 nl min‐1) then in MHS (to 21.8 ± 0.9 nl min‐1, P < 0.05). It is concluded that the blunting of the TGF resetting in response to VE in MHS rats may well be of importance in the development of hypertension in the MHS strain.
Fluoride interactions with stimulus‐secretion coupling of normal and pathological parathyroid cells
Authors: RIDEFELT P. , HELLMAN P. , RASTAD J. , LARSSON R. , AKERSTROM G. , GYLFE E.
Published: December 2008

Effects of the GTP binding protein (G‐protein) activator NaF on parathyroid hormone (PTH) release, cytoplasmic Ca2+ concentration ([Ca2+]1) and cAMP content of bovine as well as normal and pathological human parathyroid cells were studied using precautions to avoid CaF2 precipitation. In 0.5 mm external Ca2+, NaF inhibited PTH release and lowered the cAMP content by 50–70% of the effects attained with 3.0 mm Ca2+. The NaF‐induced increase of [Ca2+]1 was considerably smaller than that obtained with rise of external Ca2+. It seems likely that NaF activates the inhibitory Gi‐protein involved in the regulation of cAMP generation. However, it is unclear whether the sluggish rise of [Ca2+]1 induced by NaF is due to a direct effect of a G‐protein on Ca2+ entry, or somehow related to the G‐protein mediated formation of inositol 1,4,5‐trisphosphate, which is part of the signal transduction pathway normally initiated by Ca2+ binding to its receptor on the parathyroid cell surface. Inhibition of PTH release by NaF probably results from the combined effects on [Ca2+]1 and cAMP content. In hyperparathyroidism (HPT) the actions of NaF were not markedly affected despite severe impairments of Ca2+‐inhibited PTH release and Ca2+ triggered increase of [Ca2+]1. Consistent with observations of down regulation of the parathyroid Ca2+ receptor in HPT, the present results indicate that the disease perturbs signal transduction at a level proximal to the site of action for NaF.
Myocardial force interval relationships: influence of external sodium and calcium, muscle length, muscle diameter and stimulation frequency
Authors: MÖRNER S. E. J. N. , WOHLFART B.
Published: December 2008

Several inotropic interventions were studied in thin papillary muscles under dynamic conditions. The effects on mechanical restitution and postextrasystolic potentiation were analysed. The decay of postextrasystolic potentiation was taken as a measure of recirculation fraction of activator calcium. The mechanical restitution curve had a plateau phase on its rising phase which was abolished in low extracellular sodium hut pronounced in increased extracellular calcium. The recirculation fraction (RF) in control was 0.35±0.03; lowering the extracellular sodium by 200, increased the RF to 0.46±0.04 (n= 10). A reduction of sodium by 40%, increased the RF to 0.57±0.04, whereas increasing extracellular calcium to 4 mm gave an RF of 0.48±0.05 (n= 10 in all cases). There was no significant effect on RF of changing basic stimulation frequency or muscle preparation length. These findings support RF as a good index of myocardial contractility. Furthermore, at muscle diameters above 0.65 mm the RF was found to he reduced, suggesting this diameter as critical for muscle function. Also, postextrasystolic potentiation in relation to preceding steady state contraction was markedly increased at these diameters.

In conclusion, this study shows that RF is independent of stimulation frequency and muscle length, and that it is increased when calcium extrusion by the sodium/calcium exchange is reduced. Furthermore, RF is critically dependent upon the diameter of the preparation and mechanical restitution is changed by altered extracellular sodium concentration.
Pressure/flow relation in the peripheral pulmonary vascular bed in dogs: a preliminary study
Authors: SCHRIJEN F. , SAUNIER C. , HENRIQUEZ A.
Published: December 2008

In order to test a technique for the determination of the pressure/flow relationship in the peripheral pulmonary vascular bed, the perfusion pressure changes with increasing and then decreasing flow in a small part of the lung (around 1 ml) were studied in anaesthetized supine dogs, after insertion of a specially designed double distal lumen Swan–Ganz catheter. One lumen was used for the pressure measurement, one for infusion of saline by a pump with variable flow, from 0.1 to 1.0 ml s‐1. A conventional thermodilution Swan–Ganz catheter was also advanced in the pulmonary artery, to measure pressures in the pulmonary circulation as well as cardiac output. During infusion in the wedged catheter, right atrial, pulmonary arterial and balloon occlusion wedge pressures did not change. The pressure/flow curve of the occluded vascular bed showed a shape similar to that of collapsible tubes, with a pressure plateau at high flow, but this could also be due to vascular recruitment. The curve exhibited hysteresis, with a lower pressure when flow decreased. The slope of the initial part of the curve increased, on average, from 54±9 during normoxia to 91±27 mmHg s ml‐1during hypoxia (FIO2= 0.10); this difference was not significant, but the perfusion pressure at high flow was significantly higher during hypoxia (P < 0.05).

Using blood instead of saline would allow the determination of the peripheral pulmonary vascular resistance under physiological conditions, and further work is needed to estimate the sensitivity and the reproducibility of this technique.
The effect of rate of cooling, time of day and light regime on the shivering response in rabbits
Authors: BERGLAND H.‐P. , MERCER J. B.
Published: December 2008

In man hypothermia exists when core temperature (Te) falls below 35 °C. The onset of hypothermia is often insidious in that it can occur without any particular symptoms of serious discomfort. There is evidence that this decrease in thermosensitivity is most likely to occur when the rate of body cooling is slow. In addition there is some evidence that the susceptibility to become hypothermic varies with the circadian rhythm of Te, particularly in animals maintained under constant light conditions. A systematic investigation has been carried out to determine whether the thermoregulatory response to body core cooling is affected by the rate of change of body temperature, the time of day at which the cooling takes place and/or by the light regime under which the animals are maintained. The investigation was made in rabbits maintained either under a 12‐h light/dark (LD) cycle or under conditions of continuous light (LL). Thermosensitivity (relationship between falling Te and the induced increase in metabolic heat production) was determined at two different rates of body cooling (1 °C decrease in core temperature in either 30 or 160 min.) and at different times of the day. A chronically implanted intravascular heat exchanger was used to extract heat from the animals. The results indicate that neither the rate of body cooling nor the time of day at which the cooling took place had any clear effect on the shivering response. Likewise there was no clear difference in the shivering response of the animals maintained under (LD) conditions as compared to those maintained under (LL) conditions.
Effects of cromakalim (BRL 34915) on resting and evoked activity in frog semicircular canals
Authors: ZUCCA G. , BOTTA L. , BARBIERI A. , GRANA E. , VALLI P.
Published: December 2008

The effects of endolymphatic administration of cromakalim and glibenclamide were tested in isolated semicircular canals of the frog. The actions of the drugs were evaluated by recording: (1) the transepithelial potential between the endolymphatic and the perilymphatic sides of the crista ampullaris; (2) the slow nerve potential from the ampullar nerve; (3) the action potential discharge in afferent ampullar nerve fibres; and (4) the perilympathatic potassium concentration in the fluid bathing the outer surface of the crista ampullaris.

The above mentioned parameters were recorded both at rest and during mechanical stimulation of the sensory organ.

The results demonstrated that the endolymphatic administration of cromakalim (10‐4M) produced an increase in both ampullar receptor resting activity and in perilymphatic K+resting levels. By contrast all the parameters related to the mechanically evoked responses were practically unaffected. Glibenclamide (10‐4M) proved able to cancel or to prevent cromakalim effects. These data suggest that the membrane of the hair cells is endowed with K+channels regulated by internal ATP whose activation is mainly involved in the processes sustaining ampullar receptors' resting firing rate.
Changes in high‐energy phosphates in rat skeletal muscle during acute respiratory acidosis
Authors: THOMPSON C. H. , KEMP G. J. , RADDA G. K.
Published: December 2008

We used 31P magnetic resonance spectroscopy to study changes in phosphorus metabolite concentrations in rat skeletal muscle during respiratory acidosis (14 and 20% inspired CO2) and recovery. As intracellular pH fell (from 7.05 to 6.75 after 20 min of 20% CO2), intracellular [Pi] increased by up to 50% while phosphocreatine concentration decreased by up to 8%. The sum of all intracellular phosphates remained constant. [ADP] decreased by up to 40% in accordance with the creatine kinase equilibrium but the phosphorylation potential [ATP]/([ADP][Pi]) was preserved as a result of increased [Pi]. This adjustment may be a mechanism for maintaining mitochondrial ATP synthesis despite low pH. Eventually this increase in cellular [Pi] could lead to slow efflux of Pi from the skeletal muscle cell contributing to the hyperphosphataemia of acute respiratory acidosis.
Intra‐neural electrical stimulation of cutaneous nociceptive fibres in humans: effects of different pulse patterns on magnitude of pain
Authors: LUNDBERG L. E. R. , JØRUM E. , HOLM E. , TOREBJÖRK H. E.
Published: December 2008

A study was performed to elucidate how different impulse frequencies and impulse patterns in cutaneous nociceptive fibres influence the subjective magnitude of pain. Groups of nociceptive Aδ and C fibres were co‐activated by electrical intraneural stimulation at constant intensity in cutaneous fascicles of the peroneal nerve in healthy human subjects. The resulting pain sensations were rated on a modified visual analogue scale. Five‐second trains were administered randomly at irregular intervals of at least 30 s. Five of the stimulus patterns had regular interpulse intervals, corresponding to frequencies of 1, 2, 4, 10 and 15 Hz, and three other patterns were constructed to mimic to some extent the initially phasic and subsequently slowly adapting discharge patterns which may be encountered in recordings from human nociceptors. The results from these experiments using stimulation frequencies within physiological discharge ranges for human nociceptors indicate that the subjective magnitude of pain increases monotonously as a function of stimulus frequency, and that patterns mimicking nociceptor discharges in response to natural stimuli give rise to greater peak magnitudes of pain than artificial regular patterns with a corresponding number of impulses.
Thalamic nociceptive mechanisms in cats, influenced by central conditioning stimuli
Authors: OLAUSSON B. , SHYU B.‐C. , RYDENHAG B. , ANDERSSON S.
Published: December 2008

Field potentials and single cell activity evoked by tooth pulp (TP) stimulation were studied in the ventrobasal (VB) complex of the cat. The experiments were performed using a conditioning‐test paradigm. Evoked cell activity or field potentials following TP stimulation was used as a test. Conditioning stimulus was given to different regions of the thalamic central lateral nucleus (CL). Conditioning electrical stimulation in medial (ML 2.8‐3.6 mm) parts of CL induced a depression of the TP evoked response in 10 cells. Stimulation sites in lateral CL (ML 3.6‐4.2 mm) induced facilitation in eight cells and decreased activity in seven cells. Tooth pulp evoked field potentials in thalamus were facilitated by a preceding stimulation in lateral CL. Cells in the lateral parts of CL are suggested to induce an increased activity in cells in the VB complex which mediate nociceptive information. This effect is suggested to be mediated via a CL induced disinhibition at a reticular thalamic (RE) or at a VB complex level. The medial parts of CL seem to give a traditional feedback inhibition on VB cells. Such an effect is also suggested to be mediated via the RE complex. The importance of these findings are discussed with relation to changes in the thalamus that may occur following long lasting nociceptive stimulation.
IGF‐I binding and IGF‐I expression in regenerating muscle of normal and hypophysectomized rats
Authors: JENNISCHE E. , MATEJKA G. L.
Published: December 2008

Binding of iodinated IGF‐I to tissue sections from regenerating muscle was studied by autoradiography in normal and in hypophysectomized rats. Binding of IGF‐I was low in control muscle in both groups of animals, but increased transiently about 10‐fold during regeneration after injury. Maximal binding occurred later in hypophysectomized rats than in control rats, and there was also a slower regeneration process in these animals. IGF‐I, as demonstrated by immunohistochemistry, and IGF‐I mRNA, as demonstrated by in situ hybridization, were expressed by the regenerating muscle cells in both groups of animals. It is concluded that locally produced IGF‐I is the most likely ligand for IGF‐I receptors during muscle regeneration.
The ethanol technique of monitoring local blood flow changes in rat skeletal muscle: implications for microdialysis
Authors: HICKNER R. C. , ROSDAHL H. , BORG I. , UNGERSTEDT U. , JORFELDT L. , HENRIKSSON J.
Published: December 2008

We have investigated the feasibility of monitoring local skeletal muscle blood flow in the rat by including ethanol in the perfusion medium passing through a microdialysis probe placed in muscle tissue. Ethanol at 5, 55, or 1100 mm did not directly influence local muscle metabolism, as measured by dialysate glucose, lactate, and glycerol concentrations. The clearance of ethanol from the perfusion medium can be described by the outflow/inflow ratio ([ethanol]collected dialysate/[ethanol] Infused perfusion medium), which was found to be similar (between 0.36 and 0.38) at all ethanol perfusion concentrations studied. With probes inserted in a flow‐chamber, this ratio changed in a flow‐dependent way in the external flow range of 5–20 μl min‐1. The ethanol outflow/inflow ratio in vivo was significantly (P < 0.001) increased (to a maximum of 127±2.8% and 144±7.4% of the baseline, mean ±SEM) when blood flow was reduced by either leg constriction or local vasopressin administration, and significantly (P < 0.001) reduced (to 62±6.4% and 43±4.4% of baseline) with increases in blood flow during external heating or local 2‐chloroadenosine administration, respectively. Dialysate glucose concentrations correlated negatively with the ethanol outflow/inflow ratio (P < 0.01) and consequently decreased (to 46 ± 7.6% and 56 ± 5.6% of baseline) with constriction and vasopressin administration and increased (to 169 ± 32.5 % and 262 ± 16.7% of baseline) following heating and 2‐chloroadenosine administration. Dialysate lactate concentrations were significantly increased (approximately 2‐fold, P < 0.001) during all perturbations of blood flow. In conclusion, this technique makes it possible to monitor changes in skeletal muscle blood flow; however, methods of quantification remain to be established. The fact that blood flow changes were found to significantly affect interstitial glucose and lactate concentrations as revealed by microdialysis indicates that this information is critical in microdialysis experiments.
Influence of prostaglandins and a prostaglandin H synthase inhibitor on cervical secretion of the guinea‐pig
Authors: JONSSON B. , HAMMARSTRÖM M.
Published: December 2008

The modulatory effects of several prostaglandins and a prostaglandin H synthase inhibitor (indomethacin) on basal as well as nerve stimulation induced secretion from the cervical glands of the guinea‐pig were studied. Hypogastric nerve stimulation resulted in a secretory response of + 113%. Indomethacin dose dependently inhibited this secretory response. Prostaglandins E2, F2α and I2 inhibited and 19‐OH prostaglandin E1 reduced nerve stimulation induced secretion. Prostaglandin I2 and 19‐OH PGE1 markedly enhanced basal secretion, while indomethacin as well as PGE2 and PGF2α did not induce any secretion of cervical glands. However, PGF2α in combination with the α‐adrenergic blocker phentolamine resulted in an increase in secretion. The inhibitory effect of prostaglandins on cholinergic secretory innervation might be due to stimulation of adrenergic nerves exerting an inhibitory influence on cholinergic secretomotor innervation. It is suggested that PGI2 and 19‐OH PGE1 exert postjunctional stimulatory effects on the secretory lining and that a lack of secretory effect of PGF2α at least in part may be due to stimulatory effects on adrenergic neurons, inhibiting cholinergic secretomotor transmission. Thus, in this in vitro study it is shown that metabolites of the arachidonic acid cascade and a prostaglandin H synthase inhibitor can modulate cervical secretion and thus maybe influence fertilization.
Functional and stereologic estimations of myocardial capillary exchange capacity in treated and untreated spontaneously hypertensive rats
Authors: WÅHLANDER H. , NORDBORG C. , NORDLANDER M. , FRIBERG P.
Published: December 2008

Myocardial capillary exchange capacity was investigated by stereologic and functional techniques in parallel during pressure‐overload cardiac hypertrophy and after long‐term antihypertensive therapy with the vasodilator felodipine. In 26‐week‐old female spontaneously hypertensive rats (SHR) blood pressure increased by 25 % and left ventricular weight (LVW/BW) increased by 18% compared to Wistar‐Kyoto rats (WKY). Myocardial capillary surface and volume densities normalized for organ weight were similar in both ventricles for both strains. Moreover, capillary surface density was higher sub‐epicardially (EPI) than in the subendocardium (ENDO) in the left ventricle of SHR. Thirteen weeks of felodipine‐therapy (SHR‐Felo) normalized blood pressure without affecting LVW/BW although a transition from concentric to eccentric hypertrophy is known to occur. Myocardial capillary surface and volume densities and the left ventricular ENDO‐EPI‐gradient in surface density were similar to untreated SHR. However, felodipine‐treatment increased right ventricular weight and capillary volume density.

Functional capillary exchange was estimated in terms of permeability surface area products (PS) for Cr‐EDTA and vitamin B12 and normalized for organ weight. PScr‐EDTA, PSB12 and the ratio PScr‐EDTA/PSB12 (an index of capillary permeability) were similar in SHR and WKY. Furthermore, the relation between functional and stereological indices of exchange capacity was investigated in a multiple linear regression analysis. However, no significant correlation between PS and neither capillary surface nor volume density was found.

In conclusion, myocardial capillary exchange capacity was well adapted to the pressure overload cardiac hypertrophy present in female SHR. Despite induction of right ventricular hypertrophy, felodipine‐treatment did not affect capillary exchange capacity. Furthermore, when functional and stereologic estimates were performed in parallel, the importance of dynamic factors for myocardial capillary exchange capacity (e.g. heterogeneity) was illustrated.
Effects, release and disposal of endothelin‐1 in conscious dogs
Authors: EMMELUTH C. , BIE P.
Published: December 2008

Cardiovascular and renal responses to a step‐up infusion of endothelin‐1 (ET‐1) (1, 5, and 15 ng kg‐1 min‐1) were investigated in conscious dogs. In addition, the disappearance of ET‐l in arterial and central venous plasma after an infusion of 10 ng kg‐1 min‐1 was quantified, and the effects of vasopressin (AVP, 10 ng kg‐1 min‐1) and angiotensin II (AII, 2, 5, and 10 ng kg‐1 min‐1) on plasma ET‐1 were investigated. The step‐up infusion of ET‐1 increased the plasma level from 3.6 ± 0.3 to 243 ± 23 pg ml‐1. Concomitantly, arterial blood pressure increased and heart rate (HR) decreased dose‐dependently. Diuresis, sodium, and potassium excretion did not change significantly. However, free water clearance increased during the infusion. Clearance of creatinine and excretion of urea decreased (39 ± 4 to 29 ± 3 ml min‐1 and 87 ± 16 to 71 ± 14 μmol min‐1, respectively). Decay curves for ET‐1 in venous and arterial plasma were identical, and initial t½ was 1.1 ± 0.1 min. Vasopressin increased arterial blood pressure (107 ± 4 to 136 ± 3 mmHg) beyond the infusion period and increased plasma ET‐1 (85%). An equipressor dose of AII tended to decrease plasma ET‐1.

It is concluded that the lung is apparently not important in the removal of ET‐1, that the disappearance of ET‐1 follows a complex pattern, and vasopressin – in contrast to angiotensin II – is able to increase the plasma concentration of ET‐1. The latter may suggest that ET‐1 is involved in the prolonged pressor action of AVP observed.
Effects of somatostatin on glucagon‐stimulated glycogenolysis and gluconeogenesis in hepatocytes cultured in vitro
Authors: ROŜA J. , ROŜA J. , FIŜTER V.
Published: December 2008

The effects of somatostatin (SS‐14) on glycogenolysis and gluconeogenesis in rat hepatocytes cultured in vitro in a serum‐free medium were investigated. Somatostatin (122 nmol 1‐1) did not significantly change the basal glucose production with or without pyruvate (10 mmol 1‐1). Glucagon strongly (over 100%) increased the glucose production in hepatocytes incubated in a medium supplemented with 10 mmol 1‐1 pyruvate. This increase in glucose production is the result of increased rates of gluconeogenesis and glycogenolysis. Somatostatin partially inhibited the glucagon stimulated increase in glucose production. Glucagon also significantly increased the glucose production in a glucose‐free medium without pyruvate, which resulted from an increase of glycogenolysis. Somatostatin did not inhibit the increase in glucose production in these conditions. After a 4 h ‘fast’, glycogen in hepatocytes fell to a very low level. Glucose production was minimal. After the addition of pyruvate, there was a increase in gluconeogenesis and glucose production. Glucagon stimulated the rate of gluconeogenesis. Somatostatin completely inhibited this glucagon‐stimulated increase in gluconeogenesis.
X‐ray micro‐analysis of cultured respiratory epithelial cells from patients with cystic fibrosis
Authors: SAGSTRÖM S. , ROOMANS G. M. , WROBLEWSKI R. , KEULEMANS J. L. M. , HOOGEVEEN A. T. , BIJMAN J.
Published: December 2008

X‐ray micro‐analysis was carried out on cultured respiratory cells from polyps removed from individuals with and without cystic fibrosis (CF). In a first set of experiments, proper experimental conditions were established. Washing the cells with 300 mmol 1‐1 mannitol in distilled water was found to give the best removal of the culture medium. The elemental concentrations stabilized in about 10 min after the start of the preincubation. Intracellular [Na] and [Cl] increased slightly with increasing passage number, whereas intracellular [K] decreased. Under resting conditions there were no significant differences in elemental content between CF and control cells, and there were no indications for abnormally high total [Ca] in CF cells. In normal cells, stimulation with a cAMP‐analogue resulted in a decrease of cellular [CI], whereas in CF cells an increase was measured. Exposure of both normal and CF cells to ouabain resulted in decreased [K] and increased [Na] and [CI] level. The calcium ionophore A23187 had a similar effect on normal cells but did not affect CF cells markedly. Application of amiloride to the apical side of the cells resulted in a decrease of cellular [Na] in CF cells, whereas [Na] in control cells was not affected. The results correspond with what is known about the defective cAMP‐regulated transepithelial Cl‐transport in CF cells. The effect of the calcium ionophore on cellular electrolyte content is more complicated and may be the result of two separate effects: efflux of Cl‐ via a Ca2+‐dependent mechanism and inhibition of the Na+‐K+‐ATPase by intracellular Ca2+ ions causing an influx of Na+ and Cl‐ ions.
Functional effects of a hyperpolarization‐activated membrane current in the lobster stretch receptor neurone
Authors: Edman Å. , THEANDER S. , Grampp W.
Published: December 2008

The functional effects of a hyperpolarization‐activated membrane current (IQ) in the slowly adapting lobster stretch receptor neurone were investigated. From comparisons between changes in membrane excitability due to blockage of IQ by Cs+, in normally impaled and native unimpaled (Edman et al. 1987 b) cells, it could be concluded that the resting voltage of native cells is distinctly more negative than –65 mV (average membrane voltage of impaled cells) and, therefore, under the control of an activated IQ. Starting from this conclusion, impaled cells were polarized to holding (resting) voltages around –75 mV and their polarization and excitability properties studied after tetanic impulse activity and variation of various external influences (K+, pH, temperature), both in control conditions and after blockage of IQ by 2 mm Cs+. It was found that an unblocked IQ (a) greatly accelerates the initial (90%) decay of post‐tetanic hyperpolarization, and (b) depresses distinctly any polarization and excitability alterations due to increases in extracellular K+ concentration (from 2.5 to 10 mM), variations in extracellular pH (between 6.4 and 8.6), and changes in temperature (between 14 and 24 °C). It was inferred that in well polarized cells, IQ plays a role as a stabilizer of membrane polarization and excitability in conditions of varying external influences. From a model study of IQ it could be concluded that, with its slow dynamic responses, the current is well adapted to its functional purposes and to the rather slow homeostatic effects of the cell's Na‐K pump.
Luminal and basolateral uptake and degradation of insulin in the proximal tubules of the dog kidney
Authors: HYSING J. , ØSTENSEN J. , TOLLESHAUG H. , ANDERSEN K.J. , KIIL F.
Published: December 2008

In order to determine the major routes of insulin degradation in the body, insulin was labelled with a ‘trapped’ or ‘residualizing’ label: [125I]tyramine‐cellobiose ([125I]TC) and injected intravenously in dogs. In contrast to conventional iodine‐labelled insulin (131I‐insulin), the [125I]TC‐insulin allows measurements of total uptake in specific organs in vivo because the radioactive degradation products do not leave the cells. One h after the injection of trace doses, the amount of radioactivity recovered in the kidney from [125I]TC‐insulin was nine times higher than when conventional [131I]insulin was used. In the blood, the amount of acid‐precipitable radioactivity was the same for both labelled preparations, indicating similar clearance rates.

A comparison of the uptake of insulin in filtering vs. non‐filtering (ureter‐occluded) kidneys indicated that the uptake of insulin is twice as high through the luminal than through the basolateral cell membrane; after 60 min, 8.9 ± 0.8% of the injected [125I]TC‐insulin dose remained in the filtering kidney and 3.2 ± 0.2% of the dose was accumulated in the contralateral kidney, with occluded ureter but normal blood perfusion.

In both filtering and non‐filtering (ureter‐occluded) kidneys, the subcellular distributions of [125I]TC‐insulin were studied after various times by isopycnic sedimentation in sucrose gradients. No difference between peritubular and tubular uptake was discernible. The intracellular transport was rapid, leading to accumulation of radioactive label in dense lysosomes within 10 min.
Changes in muscle fibre type from adolescence to adulthood in women and men
Authors: GLENMARK B. , HEDBERG G. , JANSSON E.
Published: December 2008

Age‐related changes in muscle fibre characteristics have been presented in cross‐sectional studies previously. The aim of the present study was to investigate longitudinally whether the muscle fibre type composition and muscle fibre area change from adolescence to adulthood. Fifty‐five men and 28 women were studied at the age of 16 and again at the age of 27. Biopsies were taken from the vastus lateralis muscle and analysed for fibre types (I, IIA, IIB, IIC) and fibre areas. Different development of fibre type composition with increased age were seen in women and men: the type I percentage tended to increase in the women (51 ± 9 to 55 ± 12) and decrease significantly in the men (55 ± 12 to 48 ± 13). The fibre areas remained unchanged in both sexes. It is suggested that there is a sex‐related fibre adaptation to increased age.
Expression of hsp70 gene in lymphocytes from normotensive and hypertensive Humans
Authors: KUNEŠ J. , POIRIER M. , TREMBLAY J. , HAMET P.
Published: December 2008

The impact of environmental factors on hypertension depends to a certain extent on the individual's genetic background. Environmental temperature is one of the known modulators of blood pressure. We have previously demonstrated abnormal expression of a major environmentally‐controlled gene, hsp70, in hypertensive mice and rats. We have developed a simple ex vivo method for the evaluation of hsp genes expression in humans. In the present study, we investigated the accumulation of hsp70 mRNA in lymphocytes from normotensive and hypertensive humans. The data showed a higher accumulation of hsp70 mRNA in lymphocytes from hypertensives vs normotensives (2.04±0.35 vs 1.48±0.29 OD mm2, P < 0.05) submitted to heat stress (15 min at 42 °C). Basal levels were the same in both groups (0.11 ±0.01 vs 0.10±0.01 OD mm2, respectively). These results support our hypothesis that alterations in the expression of a major environmentally‐controlled gene, hsp70, may be involved in enhanced environmental responses even in human hypertension.