bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased left ventricular muscle mass after long‐term altitude training in athletes
Authors: SVEDENHAG J. , PIEHL‐AULIN K. , SKOG C. , SALTIN B.
Published: October 2003

The effects of long‐term altitude training on altitude and sea‐level physiological characteristics in elite endurance athletes were investigated. Seven Swedish elite cross‐country skiers (five men, two women; mean age 27 years) spent 1 month training at 1900 m above sea level in Italy. Rollerski treadmill tests were performed before and 5 and 11 days after the altitude sojourn; three tests were also performed at altitude. Before and 1, 11 and 35 days after the altitude camp, echocardiographic and blood volume measurements were performed. The heart rates at both maximal (P < 0.05) and submaximal (P < 0.01) work loads were decreased by 5–9 beats min−1 at altitude. The haemoglobin concentration and haematocrit increased quickly at altitude with a corresponding decrease on return to sea level. The blood volume (7%) and total haemoglobin (3%) tended to be higher day 11 post‐altitude (NS). There were no significant changes in diastolic internal diameter or wall thickness of the left ventricle, but the calculated cardiac left ventricular muscle mass was increased post‐altitude (9–10%, P < 0.01). The maximal oxygen uptake increased in six of the seven skiers after the altitude training (day 11, mean 3%, NS). In conclusion, training at moderate altitude may cause a reduction in heart rates during exercise. Moreover, after long‐term training at altitude, there may be an increase in the cardiac left ventricular muscle mass.
Effects of periodic obstructive apnoeas on superior and inferior venous return in dogs
Authors: TARASIUK A. , CHEN L. , SCHARF S. M.
Published: October 2003

Obstructive apnoeas could cause flow limitation to venous return, resulting in a decrease in cardiac output and a change in the distribution of flow from the upper and lower body. In 14 anaesthetized dogs, we studied the effects of obstructive apnoeas on inferior and superior vena caval flows under baseline conditions and with intra‐abdominal pressure increased by ≈5 torr by binding the abdomen. During obstructive apnoeas in the two groups, respiratory rate decreased by 30% (P < 0.02) and inspiratory airway pressure decreased by ≈15 torr (P < 0.01). At baseline, the ratio of inferior to superior vena caval flow was 2.4:1 and did not change with abdominal binding or apnoeas. During apnoeas there was no change in cardiac output or in the ratio of inferior to superior vena cava flow either with baseline or abdominal binding conditions. Preservation of total inferior vena caval flow during apnoeas and cardiac output occurred, even though inspiratory flow limitation was found with the abdomen bound. We conclude: (1) there was no change in either cardiac output or the distribution of venous return during apnoeas; (2) there was substantial inspiratory/expiratory variation in venous return during obstructive apnoeas. The large inspiratory increase in venous return may have implications for the development of pulmonary hypertension during obstructive apnoeas.
Pressure‐induced basilar membrane position shifts and the stimulus‐evoked potentials in the low‐frequency region of the guinea pig cochlea
Authors: FRIDBERGER A. , MAARSEVEEN J.TH.P.W. van , SCARFONE E. , ULFENDAHL M. , FLOCK B. , FLOCK Å.
Published: October 2003

We have used the guinea pig isolated temporal bone preparation to investigate changes in the non‐linear properties of the tone‐evoked cochlear potentials during reversible step displacements of the basilar membrane towards either the scala tympani or the scala vestibuli. The position shifts were produced by changing the hydrostatic pressure in the scala tympani. The pressures involved were calculated from measurements of the fluid flow through the system, and the cochlear DC impedance calculated (1.5 × 1011 kg m−4 s−1, n = 10). Confocal microscopic visualization of the organ of Corti showed that pressure increases in the scala tympani caused alterations of the position of the reticular lamina and stereocilia bundles. For low pressures, there was a sigmoidal relation between the DC pressure applied to the scala tympani (and thus the position shift of the organ of Corti) and the amplitude of the summating potential. The cochlear microphonic potential also showed a pronounced dependence on the applied pressure: pressure changes altered the amplitude of the fundamental as well as its harmonics. In addition, the sound pressure level at which the responses began to saturate was increased, implying a transition towards a linear behaviour. An increase of the phase lag of the cochlear microphonic potential was seen when the basilar membrane was shifted towards the scala vestibuli. We have also measured the intracochlear DC pressure using piezoresistive pressure transducers. The results are discussed in terms of changes in the non‐linear properties of cochlear transduction. In addition, the implications of these results for the pathophysiology and diagnosis of Meniérè's disease are discussed.
Salivary carbonic anhydrase VI concentration and its relation to basic characteristics of saliva in young men
Authors: KIVELÄ J. , PARKKILA S. , METTERI J. , PARKKILA A.‐K. , TOIVANEN A. , RAJANIEMI H.
Published: October 2003

Two successive saliva samples were collected under strictly standardized conditions from 209 healthy, selected male soldiers prior to and after breakfast in the morning and were assayed for carbonic anhydrase (CA) VI concentrations using a specific time‐resolved immunofluorometric assay. Salivary secretion rates, pH and buffer capacity pH values, and amylase activity levels were also determined. CA VI concentrations correlated positively to salivary secretion rates and amylase activity levels. By contrast, no significant correlation was seen between CA VI concentrations and pH or buffer capacity pH values, nor between amylase activity levels and salivary secretion rates, pH or buffer capacity pH values. The smokers had unaltered salivary secretion rates, CA VI and amylase activity levels, but lower salivary pH and buffer capacity pH values than the non‐smokers. Present results suggest that salivary CA VI is not directly involved in the regulation of pH in saliva.
CGRP, but not substance P, induces an increased negativity of the interstitial fluid pressure in rat trachea
Authors: GJERDE E.‐A.B. , WOIE K. , REED R.K.
Published: October 2003

Neurogenic inflammation is mediated by neuropeptides released from sensory nerves following electrical stimulation of the vagal nerve or by capsaicin. The released neuropeptides are, among others, calcitonin gene‐related peptide and substance P, which both induce vasodilation, while only substance P induces plasma extravasation. Electrical stimulation of the vagal nerve induces increased negativity of interstitial fluid pressure (Pif), which will contribute to enhance oedema formation. Pif was measured, on the abluminal side of the surgically exposed trachea, with sharpened glass capillaries (4–10 μm) connected to a servo‐controlled counterpressure system. Measurements were performed after circulatory arrest, since the oedema formation associated with acute inflammation will increase Pif in a positive direction, which may potentially underestimate the increased negativity of Pif. Experiments were carried out in pentobarbital anaesthetized (50 mg kg−1) Wistar–Møller rats. Pif in control rats averaged −1.2 ± 0.9 (SD) mmHg (n=9). Intravenous injection of capsaicin (65.0 nmol) and calcitonin gene‐related peptide (1.3 nmol) increased the negativity of Pif to −4.0 ± 1.2 mmHg (n=8)(P < 0.01) and −4.7 ± 2.0 mmHg (n=9) (P < 0.01), respectively. Intravenous injection of substance P (7.4 nmol, n=9; and 37.0 nmol, n=8) did not affect Pif compared to control (P > 0.05). Similarly, potentiation of the available substance P with thiorphan or captopril did not increase the negative Pif, nor did injection of stable substance P analogues. Thus, the present study seems to support the theory that, in rat trachea, the increased negativity of Pif after intravenous injection of capsaicin and after vagal stimulation is caused by calcitonin gene‐related peptide.
Regional difference in lipolysis caused by a β‐adrenergic agonist as determined by the microdialysis technique
Authors: Iwao N. , Oshida Y. , Sato Y.
Published: October 2003

We have investigated the difference in lipolysis caused by a β‐adrenergic agent between visceral and abdominal subcutaneous adipose tissues in vivo. Glycerol levels (lipolysis index) were continuously monitored in mesenteric and abdominal subcutaneous adipose tissues of anaesthetized Wistar rats using the microdialysis technique. During microdialysis, increasing concentrations of the lipolytic agent, isoproterenol (10−8, 10−7, 10−6, 10−5 mol L−1), were added to the perfusion. Glycerol concentrations in dialysate at each isoproterenol concentration, blood glucose concentrations during the experiment, and plasma insulin concentrations before and immediately after the experiment were measured. The effect of isoproterenol on local blood flow was investigated using the ethanol technique. The clearance rate of ethanol from the perfusion medium was used as the index of local blood flow. There was no significant change in blood glucose or plasma insulin concentrations during the study. Glycerol levels in dialysate were significantly higher in mesenteric than in abdominal subcutaneous adipose tissues at all isoproterenol concentrations. The percentage change of baseline ethanol ratio was not altered by increasing isoproterenol concentrations in both mesenteric and subcutaneous adipose tissues. There was also no significant difference in percentage change of the baseline ethanol ratio between mesenteric and abdominal subcutaneous adipose tissues. These results suggest that mesenteric adipose tissue is characterized by an even higher β‐adrenergic agonist‐induced lipolysis than abdominal subcutaneous adipose tissue.
Blubber and flipper heat transfer in harp seals
Authors: KVADSHEIM P.H. , FOLKOW L.P.
Published: October 2003

The trunk of marine mammals is encased in a blubber layer which provides thermal insulation that can be changed by circulatory adjustments. The extremities, on the other hand, are poorly insulated but have vascular arrangements constructed for prevention or promotion of heat loss, depending on the thermal state of the animal. We have studied the importance of different body parts as sites for heat dissipation and also assessed the effect of circulatory adjustments on heat transfer through blubber, by combining direct measurements of heat flux from the flippers and trunk with simultaneous recordings of temperature gradients through the blubber and metabolic rates of harp seals (Phoca groenlandica) subjected to water temperatures between 1 and 24 °C. We also determined the thermal conductivity of blubber samples from the same animals after death, and compared this with the insulative properties of live blubber. At the lowest water temperatures, the insulative properties of live blubber were similar to those of dead blubber, and heat loss from the flippers only accounted for 2–6% of the metabolic heat production. As heat load increased with increasing water temperatures, the fraction of heat lost from the flippers increased, to 19–48% at 24 °C, while the fraction lost from the trunk decreased, despite an increase in the convective (circulatory) heat transfer through the blubber layer.
Acid‐induced increase in duodenal mucosal alkaline secretion in the rat involves the L‐arginine/NO pathway
Authors: HOLM M. , JOHANSSON B. , BOTHMER C. VON , JÖNSON C. , PETTERSSON A. , FÄNDRIKS L.
Published: October 2003

Duodenal mucosal alkaline secretion increases in response to hydrochloric acid exposure. The tentative role of nitric oxide (NO) in the mediation of this response was investigated. The mucosal alkaline output by a duodenal segment was recorded by in situ titration in chloralose‐anaesthetized rats. In some experiments the duodenal blood flow was estimated by laser‐Doppler flowmetry. Exposure of the duodenum to acid (0.01 M HCl, 5 min) increased the alkaline secretion by ≈85%. The NO synthase inhibitor NG‐nitro‐L‐arginine methyl ester (L‐NAME, 10 mg kg−1 intravenously or 0.3 mM intraluminally) blocked the secretory increment after mucosal acid exposure. Mean arterial pressure and basal alkaline secretion were markedly raised, whereas duodenal blood flow was decreased, when L‐NAME was given intravenously (i.v.). Intraluminal (i.l.) administration left mean arterial pressure as well as duodenal blood flow unaltered, and the duodenal mucosal alkaline secretion was only slightly elevated. The stereoisomer NG‐nitro‐D‐arginine methyl ester (D‐NAME) had no effect on either basal or acid‐induced duodenal alkaline output. In animals receiving L‐arginine (10 mg kg−1 min−1 i.v., or 3 mM i.l.) and L‐NAME, the acid exposure elicited an increase in duodenal mucosal alkaline secretion, similar to that observed in controls.

The results suggest that the acid‐induced increase in duodenal mucosal alkaline secretion involves NO synthesis, which takes place close to the lumen, probably within the mucosa.
The motor unit potential distribution over the skin surface and its use in estimating the motor unit location
Authors: ROELEVELD K. , STEGEMAN D.F. , VINGERHOETS H.M. , OOSTEROM A. VAN
Published: October 2003

The amplitude of a surface electromyogram is dependent on the number of active motor units, their size and the relative position of the recording electrode. It is not possible to interpret the surface electromyogram quantitatively without disentangling these different aspects. In this study the decline of different components of the motor unit potential with increasing radial distance from the motor unit is quantified. Fifty‐two motor units in the biceps brachii muscle were studied using 36‐channel surface electromyography combined with intramuscular scanning electromyography. Scanning electromyography was used to locate precisely the motor unit. The dependence of the surface motor unit potential magnitude on the radial distance between the motor unit and the recording electrodes can be described fairly well by an inverse power function. The steepness of this function depends on the chosen motor unit potential parameter and the interelectrode distance, but also varies between motor units. The change of the negative peak amplitude of the motor unit potential over the skin surface can be used to give a fairly accurate estimate of the location of the motor unit under the skin surface. We found that for all practical purposes the depth of a motor unit in the biceps brachii muscle can be estimated as 20% of the distance over the skin surface where motor unit potentials can be recorded with higher amplitudes than 50% of the maximal amplitude recorded at the skin surface caused by activity of the same motor unit.
pH and smooth muscle
Authors: AALKJÆR C. , PENG H.‐L.
Published: October 2003

In this paper, the control of vascular smooth muscle intracellular pH (pHi) and the mechanisms of importance for the vasodilation to acidosis are reviewed. The three transport pathways of importance for the control of pHi are a sodium‐coupled bicarbonate transport, a Na,H‐exchanger and a Cl,HCO3−exchange. While the two latter pathways are present in all smooth muscle cells studied, the sodium‐coupled bicarbonate transport may be present in two forms which are either coupled to chloride efflux or are independent of chloride. The chloride‐independent pathway seems electroneutral, indicating a 1:1 stoichiometry. All three transporters can be activated by vasoactive hormones and the second messengers involved are under intense investigation. With respect to the mechanisms involved in the vasodilation to acidosis, there seems to be a nitric oxide‐dependent pathway as well as a direct effect of acidosis on the smooth muscle cells. In some preparations, prostanoids may also be involved. The direct vasodilator effect of acidosis is probably mediated through reduction of extracellular pH and the acidosis is associated with a reduction of the intracellular calcium concentration, which could explain the reduction of smooth muscle tone.
Role of hyperglycaemia‐related acidosis in ischaemic brain damage
Authors: LI P.‐A. , SIESJÖ B.K.
Published: October 2003

Although previous results have shown unequivocally that pre‐ischaemic hyperglycaemia aggravates brain damage due to transient ischaemia, several questions have remained unanswered. First, is the effect of hyperglycaemia due to a further fall in intra‐ and extracellular pH? Second, is aggravation of damage a step function or a continuous function of plasma glucose concentration or of pH? Third, which are the mechanisms responsible for aggravation of damage, notably for the transformation of selective neuronal damage to infarction, for oedema development, and for post‐ischaemic seizures? Recent results have provided new information on all of these issues. Thus, normoglycaemic animals with superimposed hypercapnia showed a similar, albeit not identical, aggravation of ischaemic damage, suggesting that acidosis is one major mediator. Furthermore, experiments with graded increase in plasma glucose concentration revealed a threshold effect at values of 10–12 mM, while microelectrode measurements showed a narrow extracellular pH range (6.4–6.5) for post‐ischaemic seizure development. These results suggest that aggravation of damage due to excessive acidosis is due to mechanisms with a steep pH dependence. Finally, results are now at hand suggesting that the effect of acidosis is not mediated by a further perturbation of cell calcium metabolism. The more likely mediators are free radicals. Thus, acidosis is known to enhance iron‐catalysed production of reactive oxygen species, probably by releasing iron from its bindings to transferrin, ferritin and other proteins.
Immunohistochemical localization of gastrin/CCK‐B receptors in the dog and guinea‐pig stomach
Authors: HELANDER H. F. , WONG H. , POORKHALKALI N. , WALSH J. H.
Published: October 2003

Gastrin/CCK‐B receptors are involved in the regulation of several types of cells of the gastric mucosa, including the parietal cells, the ECL cells and the D cells. In this study, we aimed at localizing such receptors in the gastric mucosa. For this purpose, we prepared monospecific antibodies against two sequences of the canine gastrin/CCK‐B receptor. Sections of formalin‐fixed, paraffin‐embedded corpus and antrum from dog and guinea‐pig were immunostained with these antibodies. In parallel, sections were stained with antibodies against somatostatin. Staining with gastrin/CCK‐B receptor antibodies was observed in a few, small epithelial cells in the bottom part of the corpus mucosa. Immunoreactive cells of the antral mucosa were structurally similar, but more frequent. The same cells also stained with somatostatin antibodies. In addition, one of the gastrin/CCK‐B antibodies reacted with canine submucosal smooth muscle cells. No staining was observed in sections exposed to antibodies that were pre‐absorbed with the corresponding antigen. We conclude that gastrin/CCK‐B receptors are present in D cells of the gastric mucosa and in submucosal smooth muscle cells.
A comparison of the lipolytic and anticoagulative properties of heparin and pentosan polysulphate in the thoroughbred horse
Authors: ORME C. E. , HARRIS R. C.
Published: October 2003

The aim of the study was to develop a model for the pre‐exercise elevation of plasma free fatty acids in the horse, with a view to its future use in investigations of fat metabolism during exercise. A comparison of the lipase releasing and anticoagulative effects of heparin and a related substance pentosan polysulphate was investigated. Furthermore, the ability of heparin and pentosan polysulphate to affect an increase in plasma free fatty acid concentration, when co‐administered with a triglyceride emulsion, was quantified. Doses of 0.39 and 1.3 mg kg−1 body wt of heparin and pentosan polysulphate respectively, administered intravenously, resulted in a significant increase in plasma total lipase activity (P<0.001). There was, however, no significant difference in plasma lipase activity between treatments. Heparin resulted in a mean 14±6.5‐fold increase in activated partial thromboplastin time compared with a mean 1.6±0.1‐fold increase with pentosan polysulphate. Both heparin and pentosan polysulphate when co‐administered with a triglyceride emulsion (Iverlip 20) resulted in a significant increase in plasma free fatty acid concentration (P<0.001), although there was no significant difference between treatments. Thus, whereas a higher dose of pentosan polysulphate elicited a comparable lipolytic effect to heparin, including significant elevation of plasma free fatty acids, this was associated with a much reduced effect upon clotting function. Pentosan polysulphate, therefore, represents a suitable alternative to heparin for the elevation of plasma free fatty acids before exercise when used in conjunction with a triglyceride emulsion.
Influence of ingesting a solution of branched‐chain amino acids on perceived exertion during exercise
Authors: BLOMSTRAND E. , HASSMÉN P. , EK S. , EKBLOM B. , NEWSHOLME E. A.
Published: October 2003

On two occasions, seven male endurance‐trained cyclists performed exhaustive exercise on a cycle ergometer in the morning after they had performed a bout of exercise the preceding evening in an attempt to lower the muscle glycogen stores. The subjects exercised at a work rate corresponding to ≈70% of their maximal oxygen uptake for 60 min, followed by another 20 min of maximal exercise. During exercise the subjects were given either a solution of branched‐chain amino acids (BCAAs) or flavoured water (placebo). Every 10 min during exercise the subjects rated their perceived exertion and mental fatigue on two different Borg scales. During the 60 min exercise at a given work rate, the subjects' ratings of perceived exertion when they were given BCAAs were 7% lower, and their ratings of mental fatigue were 15% lower, than when they were given placebo. In addition, the performance in the colour task of Stroops' Colour Word Test performed after exercise was improved when BCAAs had been ingested during exercise, compared with the results from the placebo trial. There was no difference in the physical performance between the two trials, measured as the amount of work done during the last 20 min of exercise when the subjects performed at their maximum. The plasma concentration ratio of free tryptophan/BCAAs, which increased by 45% during exercise and by 150% 5 min after exercise in the placebo trial, remained unchanged or even decreased when BCAAs were ingested.
Peripheral circulatory effects of pump perfusion on cat skeletal muscle with and without prostacyclin
Authors: JAHR J. , GRÄNDE P. O.
Published: October 2003

The present study analyses the peripheral circulatory effects of pump perfusion on a sympathectomized cat skeletal muscle in terms of effects on segmental vascular resistances (large‐bore arterial vessels, arterioles and veins), hydrostatic capillary pressure, capillary filtration coefficient, transcapillary filtration and autoregulation of blood flow. The effect of prostacyclin during pump perfusion was analysed to evaluate whether it interferes with the pump‐induced vascular alterations, especially if it reduces transcapillary filtration through its capillary permeability decreasing effect. Pump perfusion initiates a marked vasodilation (from 17.3 to 10.1 PRU), an increase in hydrostatic capillary pressure, and a marked inhibition of myogenic reactivity and of autoregulation of blood flow. There was a slow restoration of vascular tone reaching a steady‐state level somewhat below the autoperfusion value within 2 h. Pump perfusion did not change the capillary filtration coefficient, indicating that the capillary permeability was not increased. This implies that short‐term pump‐induced capillary leakage is more an effect of increase in hydrostatic capillary pressure, perhaps in combination with increased number of open capillaries, than of an increase in capillary permeability. Prostacyclin decreased capillary permeability by at least 22% but simultaneously increased hydrostatic capillary pressure, resulting in an unchanged filtration compared with the situation just after the starting of the pump. The results obtained show that experiments using pump perfusion should be interpreted with care due to the interference with normal peripheral vascular control. The results give reasonable explanations of the lowered blood pressure and transcapillary fluid loss during the clinical use of a heart‐lung machine.
Cerebral blood flow of the exposed brain surface measured by laser Doppler perfusion imaging
Authors: KIMME P. , GUSTAFSSON U. , SOLLEV A. , NILSSON G. , SJÖBERG F.
Published: October 2003

A novel application of laser Doppler flowmetry (LDF), laser Doppler perfusion imaging (LDPI), was used to study cerebral cortical blood flow (CBFcortex). In contrast to the conventional laser Doppler perfusion monitor, LDPI creates two‐dimensional maps of the tissue perfusion in a well defined area of up to 120×120 mm comprising 4096 measurement points. Measurements of CBFcortex were made through an optically transparent polyester film applied to a cranial window preparation in ventilated anaesthetized pigs. Temporal and spatial heterogeneity in CBFcortex were visualized by LDPI during provocations which are known to alter CBF (varying arterial PCO2 or MABP, or infusion of adenosine at constant MABP (concomitant angiotensin administration) or by hyperoxemia). During hypercapnia the recorded CBFcortex increased homogeneously. The adenosine‐mediated increase in recorded CBFcortex was concentrated on the lower flow interval, as was the hyperoxemia‐caused decline. At decreasing MABP the autoregulatory threshold was found to vary locally within the cortex. The results suggest that LDPI, apart from detecting localized changes in CBFcortex, also visualizes flow changes within different vascular segments. Together with the practical advantages of the system, i.e. not necessitating direct contact with the tissues, this feature makes the technique suitable for studies of CBFcortex distributions.
The conservation of mitochondrial function by ischaemia – the ischaemia paradox
Authors: STEINMANN C. M. L. , STORM M.
Published: October 2003

The aim of this study was to compare oxidative phosphorylation of rat heart mitochondria, isolated: (i) immediately after excision of the heart; (ii) after 60 min of low flow normoxic perfusion; (iii) after 60 min of high flow normoxic perfusion; (iv) after 30 min of no‐flow ischaemia and (v) after 30 min ischaemia followed by 20 min reperfusion. The results, using a retrogradely perfused rat hart as a model, show that mitochondrial oxidative phosphorylation after 30 min of no‐flow ischaemia showed no difference from oxidative phosphorylation measured on mitochondria isolated directly after excision of the heart. However, after 30 min no‐flow ischaemia followed by 20 min of reperfusion, oxidative phosphorylation deteriorated in comparison with oxidative phosphorylation after 30 min of ischaemia only. Furthermore, oxidative phosphorylation after 60 min of non‐ischaemic high flow perfusion (thus high coronary flow), compared better with oxidative phosphorylation after ischaemia‐reperfusion than with oxidative phosphorylation after ischaemia alone.
Step vs. progressive exercise: the kinetics of phosphocreatine hydrolysis in human muscle
Authors: BINZONI T. , HILTBRAND E. , YANO T. , CERRETELLI P.
Published: October 2003

It is well known that the VPO2 readjustment rate of the whole body is faster when carrying out a given constant work load starting from a baseline of moderate exercise than from rest. However, it has not been established whether the above change is the result of faster kinetics of the oxidative machinery or, alternatively, the consequence of a reduced involvement of confounding factors such as anaerobic glycolysis or tissue O2 stores. The problem, earlier approached by chemical methods, was studied in man by 31P‐NMRS assessment of the kinetics of phosphocreatine (PC) hydrolysis at the muscle level which is known to reflect the readjustment rate of the oxidative reactions. Twelve normal subjects carried out in a 90 cm bore modified Picker (1.5 T) magnet, a series of contractions by the plantar flexors reaching pre‐set submaximal loads either in single steps (constant load, CL) or progressively (incremental exercise, I). If preceding exercise (I), compared to rest, influenced the rate of oxidations, the PC concentration at the target loads would be different for the two exercise modes, reflecting different energy deficits. This was not the case. Thus the present results show that the rate of readjustment of oxidations at the muscle level is not affected by priming exercise confirming previous findings and showing that theoretical models of VPO2 control are experimentally applicable to man.
Plasma angiotensins and human forearm circulation: effects of sympatho‐adrenal activation
Authors: KAHAN T. , LINDQVIST M. , NUSSBERGER J. , MELCHER A. , HJEMDAHL P.
Published: October 2003

Complex interactions appear to exist between the renin–angiotensin system and sympathetic neurotransmission, and sympathetic activity may influence local angiotensin II formation. Arterial and forearm venous plasma levels of angiotensin I and II were therefore studied in 11 healthy males at rest, during sympathetic activation elicited by mental stress, and during adrenaline induced vasodilation. Specific assays for angiotensin‐(1–8) octapeptide and for angiotensin‐(1–10) decapeptide (i.e. angiotensin II and I, respectively), were used. Special precautions to minimize ex vivo formation and/or degradation of angiotensins were employed. Mental stress increased regional noradrenaline overflow three‐fold, with a concomitant three‐fold increase in forearm blood flow, whereas intravenous adrenaline infusion increased forearm blood flow two‐fold and noradrenaline overflow four‐fold. There was a constant positive veno‐arterial concentration difference for angiotensin I under all conditions tested, compatible with local angiotensin I formation. We found no veno‐arterial concentration difference for angiotensin II or regional net angiotensin II overflow under the conditions tested. These results in the forearm circulation support previous animal experimental evidence in skeletal muscle and provide no evidence in favour of a de novo formation of angiotensin II in skeletal muscle in vivo during basal conditions. Furthermore, sympathetic nerve stimulation does not seem to enhance angiotensin II generation importantly in this vascular bed.
Perivascular dendritic cells of the human dental pulp
Authors: OKIJI T. , JONTELL M. , BELICHENKO P. , BERGENHOLTZ G. , DAHLSTRÖM A.
Published: October 2003

The morphological and phenotypical features of the class II molecule (HLA‐DR) expressing cells in human dental pulps were compared with those of previously characterized perivascular dendritic cells in the dermis. We have further investigated how these pulpal cells are structurally related to the vascular system. Double‐immunofluorescence staining revealed that a substantial portion of the pulpal HLA‐DR expressing cells also expressed factor XIIIa, a marker for dendritic cells. The cells usually had a highly dendritic appearance and formed a reticular network in the pulpal connective tissue. The majority of cells also expressed macrophage‐related antigens (CD14 and CD68). A small but distinct population of pulpal cells, representing approximately 13% of the class II molecule expressing cells, was devoid of a typical macrophage phenotype. This subpopulation of pulpal cells may be similar to dendritic cells present in the dermis. Confocal laser scanning microscopy showed that highly dendritic cells, found in close relation to the endothelium, had dendritic processes which were found to be in contact with the peripheral cell membrane of the endothelial cells. These cells formed a three‐dimensional structure around the microvessel resembling a cellular conduit. We conclude that the human dental pulp is equipped with class II molecule‐expressing perivascular dendritic cells composed of a heterogeneous cell population.
Heterogeneous blood flow response in the foot on dependency, assessed by laser Doppler perfusion imaging
Authors: GOLSTER H. , THULESIUS O. , NILSSON G. , SJÖBERG F.
Published: October 2003

The exact nature of the decrease in foot skin blood flow seen after a change in posture remains unsettled. This mechanism has previously been examined by non‐invasive techniques such as the laser Doppler perfusion monitor (laser Doppler flowmetry). Taking into account the shortcomings of laser Doppler perfusion monitoring when applied to the determination of skin blood flow, which normally shows substantial heterogeneity, we have applied an emerging technology, the laser Doppler perfusion imager (LDPI). This technique provides a more comprehensive picture of the blood flow distribution in the skin, as it maps skin blood flow over a surface area (120×120 mm, 4096 measurement sites). It was used to examine if the reduction in tissue perfusion or the alterations in flow distributions seen after a change in posture (supine to dependency) could be fully explained by an increase in venous pressure (venous stasis of 50 mmHg) or if the data suggest a complementary mechanism.

Skin blood flow of the forefoot decreased from 0.60 V (volt) (median) during rest to 0.40 and 0.38 V during venous stasis and dependency, respectively. Although almost identical median values were obtained during stasis and dependency, the flow distributions were different, with a loss of high flow values during venous stasis. Biological zero was 0.24 V.

As the LDPI technique readily records skin perfusion during variations in venous stasis and posture, as well as information on flow distribution changes, it appears promising for future application in stimuli‐response studies of skin blood flow. The difference in flow distribution seen between increased venous pressure and dependency suggests an additive regulatory mechanism to the veni‐vasomotor reflex during a change in posture.
Proliferation and differentiation of cells from explants of fetal rat stomach
Authors: TØMMERÅS K. , CHEN Y. , RHEDIN M. , CABERO J. L. , MÅRDH S.
Published: October 2003

The current understanding of the mechanisms controlling the proliferation and differentiation of the stem cells of the gastric oxyntic glands is limited. The aim of the present study was to develop a method for investigating proliferation and differentiation of undifferentiated cells from fetal rat stomach. Outgrowth of cells was initiated from explants of 16‐day‐old fetal rat stomachs. At this stage of the fetal development the gastric epithelial cells are undifferentiated. The explants were cultured in DMEM/F‐12 medium supplemented with fetal calf serum only, or fetal calf serum combined with either hydrocortisone or pentagastrin. Morphological characterization by means of light microscopy, dye staining and immunostaining was used to identify the growing cells. Both hydrocortisone and pentagastrin accelerated the differentiation towards H,K‐ATPase‐positive cells, mucus‐producing cells and other epithelial cells. H,K‐ATPase‐positive cells, which were identified by immunostaining with a monoclonal antibody reacting with the α‐subunit of the H,K‐ATPase, grew on top of the confluent layer of epithelioid and fibroblastoid cells. With this method in vitro investigations of the mechanisms of proliferation and differentiation of gastric mucosal cells are possible. Although by different mechanisms, both hydrocortisone and pentagastrin appear to play a regulatory role in these processes.
Effect of ovariectomy upon weaning on the morphometric parameters of femorae and tibiae of growing rats
Authors: HIETALA E.‐L. , LARMAS M.
Published: October 2003

To assess the effects of early ovariectomy on whole bone density and several morphometric and serum markers of bone metabolism female Wistar rats were ovariectomized or sham‐operated upon weaning. The animals were fed ad libitum. After 8 weeks the increase in the weight gains of ovariectomized rats was minute when compared with the control animals. The whole bone densities of the femorae of ovariectomized rats were slightly reduced when compared with the sham‐operated animals. The proximal cross section of the femorae of the ovariectomized rats exhibited enhanced periosteal bone apposition and increased cortical area when compared with the sham‐operated animals but the differences were not statistically significant. The cancellous bone of the femora and the proportional areas of trabeculae of the proximal tibia were reduced in ovariectomized rats. It is concluded that ovariectomy upon weaning caused a clear tendency toward osteopenia. Cancellous bone was clearly affected after ovariectomy indicating its relation to gonadal hormone regulation even during growth.
Influence of picrotoxin and strychnine on the spectral sensitivity of the turtle ERG b‐ and d‐waves: II. Light adaptation
Authors: VITANOVA L. , KUPENOVA P. , POPOVA E. , MITOVA L.
Published: October 2003

The aim of the present work was to investigate the role of GABA and glycine, the two main inhibitory neurotransmitters in the retina, in the spectral sensitivity coding under conditions of light adaptation. To study this question, spectral sensitivity curves, based on the turtle ERG responses to stimuli of different wavelengths, were constructed. The spectral sensitivity curves, obtained before and during treatment with picrotoxin (PT), a GABAA antagonist, or with strychnine (ST), a glycine antagonist, were compared. Both PT and ST increased the b‐ and d‐wave absolute sensitivity in a wavelength‐dependent manner. PT significantly changed the shape of the b‐ and d‐wave spectral sensitivity curves and the latter lost their peaks.

It is concluded that, under conditions of light adaptation, GABA and glycine took part in the formation of the b‐ and d‐wave spectral sensitivity curves, that both of them exerted an effect on the gain and that, furthermore, GABA had a well pronounced effect on the tuning of the spectral sensitivity curves.
Distribution of pulmonary ventilation and perfusion measured simultaneously in awake goats
Authors: MELSOM M. N. , KRAMER‐JOHANSEN J. , FLATEBØ T. , MÜLLER C. , NICOLAYSEN G.
Published: October 2003

Gravity has been regarded as the major determinant for local pulmonary perfusion and ventilation. Recent reports, describing major gravity‐independent heterogeneity in both variables, have questioned the importance of gravity. We asked to what extent ventilation and perfusion were related, and if they showed similar distributions along the vertical axis in the lung. We gave 99mTc‐aerosols as tracers for ventilation and radioactive microspheres as blood flow tracers in five awake goats over 4 min. Ventilation and perfusion were determined in ∼1.5 cm3 pieces of the lung. For both variables the vertical distribution could vary considerably from lung to lung, but within each lung the two distributions were similar. Both ventilation and perfusion were heterogeneously distributed (CV ∼40% for both), they were highly correlated (r=0.81) and the average 25–75‐interpercentile interval for ventilation to perfusion ratio (0.84–1.13) was significantly less wide than for both ventilation (0.76–1.38) and perfusion (0.76–1.40). Some pieces were considerably overventilated while few were correspondingly underventilated. This could indicate that perfusion is adjusted to ventilation in normoxic lungs with a low sensitivity to overventilation.
Cystatin C, an inhibitor of bone resorption produced by osteoblasts
Authors: LERNER U.H. , JOHANSSON L. , RANSJÖ M. , ROSENQUIST J.B. , REINHOLT F.P. , GRUBB A.
Published: October 2003

The effects of human cystatin C on bone resorption, enzyme release, osteoclast generation, bone cell proliferation and bone matrix protein biosynthesis have been examined in different in vitro systems. The effects of cystatin C were compared with those of calcitonin and E 64 (trans‐Epoxysuccinyl‐L‐leucyl‐amido‐(4‐guanidino)butane). Recombinant human cystatin C and E 64 dose dependently inhibited the mobilization of 45Ca and the release of 3H (from []>
3H]‐proline‐labelled bones) in mouse calvariae stimulated to resorb by parathyroid hormone (PTH) or 1,25(OH)2‐vitamin D3. Cystatin C and E 64 also inhibited the release of 45Ca from bones stimulated by thrombin, interleukin‐1 and prostaglandin E2. In PTH‐stimulated bones, the inhibitory action of cystatin C and E 64 on 45Ca release was observed after 6–9 h, whereas the inhibitory effect on 3H release was seen after just 2 h. In contrast, calcitonin caused an inhibition of both 45Ca and 3H release which was seen after 2 h. The PTH‐stimulated release of the lysosomal enzymes was not affected by cystatin C and E 64, whereas calcitonin caused a significant inhibition. In contrast to calcitonin, cystatin C did not affect PTH‐stimulated enhancement of osteoclast generation in the mouse calvariae. Using Western blot analysis and radioimmunoassay, we demonstrated that mouse calvarial bones and MC3T3‐E1 cells produce cystatin C. These data show that cystatin C is synthesized by bone cells and that recombinant human cystatin C inhibits bone resorption in vitro without affecting bone cell proliferation, bone matrix formation or osteoclast generation. The mechanism seems to be due primarily to inhibition of the activity of osteoclastic proteolytic enzymes released into the resorption lacunae.
BK channels in intact clonal rat pituitary cells are activated by physiological elevations of the cytosolic Ca2+ concentration at the normal resting potential
Authors: HAUG T. , SAND O.
Published: October 2003

Activation of large conductance Ca2+‐activated K+ channels (BK channels) in intact clonal rat pituitary cells (GH4 cells) was investigated using the cell‐attached patch‐clamp configuration. This method prevents loss of intracellular factors which might influence channel activity. BK channels are generally considered to be inactive at the resting membrane potential in excitable cells. However, at the resting potential (0 mV pipette potential), 40% of the cell‐attached patches displayed spontaneously active BK channels, which remained active even at 20 mV hyperpolarization. The peptide thyroliberin (TRH) elevates the cytosolic Ca2+ concentration ([
Ca2+]i) in GH cells by IP3‐induced release of Ca2+ from intracellular stores. This rise in [Ca2+]i occurs concomitantly with membrane hyperpolarization. TRH stimulation caused activation of BK channels in nine out of 30 silent cell‐attached patches, and caused enhanced channel activity in seven out of 29 cell‐attached patches containing spontaneously active BK channels. The Ca2+ ionophore ionomycin activated silent BK channels in three out of 10 cell‐attached patches, and increased the activity of spontaneously active BK channels in seven out of 16 cell‐attached patches. The pipette potential was clamped to 0 mV in all these experiments. We conclude that the BK channels in GH4 cells may be active at the resting membrane potential and more negative membrane potentials. The channels may also be activated further by physiological elevations of [Ca2+]i in the same potential range. Our results point towards new possible physiological roles for the BK channels in GH4 cells. This is in agreement with the emerging picture of BK channels highly sensitive to [Ca2+]i in a wide variety of cell types.
Effects of stimulation and inhibition of protein kinase C on the cytosolic calcium concentration in rabbit afferent arterioles
Authors: SALOMONSSON M. , KORNFELD M. , GUTIERREZ A.M. , MAGNUSSON M. , PERSSON A.E.G.
Published: October 2003

The effect of the protein kinase C (PKC) inhibitor chelerytrine (Ch) and the PKC activator 12–0‐tetradecanoyl‐phorbol‐13‐acetate (TPA) on the cytosolic calcium concentration ([ Ca2+]i) in isolated intact rabbit afferent arterioles was investigated. [Ca2+]i was measured in the proximal and distal parts of the arteriole. Administration of 1 μM Ch gave rise to a peak followed by an elevated level of [Ca2+]i in both these parts. Neither the peak nor the elevated level of [Ca2+]i was significantly reduced by 1 μM nifedipine. The relative peak increase in [Ca2+]i in response to 1 μM noradrenaline (NA) or to 10 nM angiotensin II (AII) was significantly blunted in both parts after preincubation with 1 μM Ch. Depolarization with 25 mM K+ increased [Ca2+]i in both parts. Preincubation with Ch did not affect the increase in [Ca2+]i induced by 25 mM K+. TPA (10 and 100 nM) did not significantly affect the basal [Ca2+]i in the afferent arteriole. The [Ca2+]i response to NA or 25 mM K+ was not affected by TPA. We conclude that blockade of PKC increases [Ca2+]i in afferent arteriolar smooth muscle by a mechanism independent of L‐type voltage‐sensitive calcium channels. Inhibition of PKC blunts the relative increase in [Ca2+]i in response to AII and, to a lesser extent, that induced by NA. We conclude that PKC might be important in modulating the calcium changes that occur in response to these vasoconstrictors.
Resistance of Helicobacter pylori to antibiotics
Authors: MÉGRAUD F.
Published: October 2003

Resistance of Helicobacter pylori to antibiotics included in current regimens used to eradicate H. pylori is a major reason for failure. The definition of resistance is not simple, and the clinical relevance of in vitro results must be considered. The different methods of testing antibiotics cannot apply in all cases.

Resistance to clarithromycin has a low prevalence rate (<10%) and its mechanism is well defined (point mutation on the 23S rRNA genes, and decreased binding of the antibiotics to the ribosome). Its clinical relevance is not questioned and, because of a clear occurrence of a bimodal strain population, the method for detecting resistance is not crucial.

Resistance to nitroimidazoles is much more common, probably in the range of 30% or more in Europe. Neither the mechanism of action of metronidazole resistance nor its mechanism of is well known. The redox potential inside the cell which is important in reducing metronidazole to its active metabolite is probably a key element, but the exact metabolites involved are not yet known. Metronidazole resistance was found to be clinically relevant when standard triple therapy was used. The relevance is questioned for triple therapies including a proton pump inhibitor, clarithromycin and metronidazole. More clinical data are needed in this field and the use of agar dilutions is recommended to assess the susceptibility of H. pylori to metronidazole.

The mechanism of resistance to quinolones has been described but these compounds are not currently used for H. pylori infection. No resistance has yet been described for amoxycillin but continuous surveillance is needed in order to detect new cases, as was recently the case for tetracycline resistance.
The role of antisecretory drugs in the treatment of Helicobacter pylori infection
Authors: PETERSON W. L.
Published: October 2003

The efficacy of antibiotics against Helicobacter pylori is enhanced by the co‐administration of antisecretory drugs. While proton pump inhibitors appear to have some direct effect on H. pylori and extreme hypochlorhydria has a deleterious effect on the organism, the most likely mechanism by which antisecretory drugs as a class provide this effect is by improving the efficacy of the antibiotics themselves. Although proton pump inhibitors are the most widely used antisecretory agents, H2 receptor antagonists also enhance antibiotic effects.