bluuebunny/crossref_metadata_2025 huggingface dataset:
Atropine abolishes electroencephalogram‐associated heart rate changes without an effect on respiratory sinus arrhythmia during anaesthesia in humans
Authors: YLI‐HANKALA A. , LOULA P. , ANNILA P. , LINDGREN L. , JANTTI V.
Published: December 2008

Heart rate fluctuates with the electroencephalogram burst suppression pattern during anaesthesia: increasing at burst onset and decreasing at suppression. Heart rate also oscillates with positive pressure ventilation. The effects of atropine on these heart rate changes were studied in 12 patients during isoflurane anaesthesia and positive pressure ventilation at a frequency of 6 cycles min‐1. Four additional patients served as controls. A bolus dose of atropine (20µg kg‐1 intravenously) abolished the electroencephalogram‐correlated heart rate changes; however, the amplitude of respiratory sinus arrhythmia was not changed after atropine. The control mechanism of the burst suppression pattern in electroencephalogram also affects parasympathetic heart rate control. The control mechanisms of respiratory sinus arrhythmia during anaesthesia with positive pressure ventilation differ from those during spontaneous breathing awake.
Non‐uniform recovery of performance in stunned myocardium evaluated by two‐dimensional sonomicrometry
Authors: RYNNING S. E. , HEXEBERG E. , BIRKELAND S. , WESTBY J. , HESSEVIK I. , GRONG K.
Published: December 2008

The objective of the present study was to assess the uniformity of contraction in reperfused myocardium. Regional function was measured by two pairs of piezoelectric crystals oriented in the circumferential and longitudinal axis of the left ventricular anterior midwall in 10 open‐chest pentobarbitone‐anaesthetized cats. The left anterior descending coronary artery was occluded for 10 min followed by 60 min of reperfusion. Myocardial blood flow was measured four times by radioactive labelled microspheres: at pre‐occlusion, occlusion and after 30 and 60 min of reperfusion. There was a severe and transmural homogenous ischaemia during coronary occlusion. The recovery of ejection shortening was on average 76% at 30 min and 77% at 60 min of reperfusion in circumferential segments versus 25 and 44% in longitudinal segments (P <0.05). Diastolic function was deranged in longitudinal segments; at 60 min of reperfusion the end diastolic pressure‐length relation was still shifted rightwards in longitudinal segments, whereas it was normalized in circumferential segments. In conclusion, systolic and diastolic dysfunction in stunned myocardium were more severe in the longitudinal axis than in the circumferential axis of the feline heart. This indicates that stunning was more pronounced in longitudinally oriented sub‐endocardial fibres which were reflected by the longitudinal segment, despite transmural homogenous ischaemia during coronary artery occlusion.
The role of the L‐arginine/nitric oxide pathway for relaxation of the human lower oesophageal sphincter
Authors: TØTTRUP A. , NY L. , ALM P. , LARSSON B. , FORMAN A. , ANDERSSON K.‐E.
Published: December 2008

Smooth muscle specimens were taken from the oesophagogastric junction (OGJ) in patients operated on for gastrointestinal malignancies not involving the OGJ. The smooth muscle bundles of the inner, circular layer of the OGJ were richly innervated by fine nerve fibres staining positively for NADPH diaphorase. The outer longitudinal layer had a markedly lower number of NADPH‐diaphorase positive nerve fibres. When the preparations were suspended in organ baths for recording of isometric tension, they developed active tension. Transmural field stimulation (TMS) induced frequency‐dependent relaxations, which were abolished by NG‐nitro‐L‐arginine (L‐NNA; 10‐4M), and were often converted to atropine‐sensitive contractions. The effect of L‐NNA was concentration‐dependent, and the concentration‐response curve for L‐NNA was shifted to the right by L‐arginine pre‐incubation. The enantiomerNG‐nitro‐D‐arginine (10‐4M) also showed inhibitory actions on the responses to TMS, but significantly less than L‐NNA. Relaxant responses to vasoactive intestinal polypeptide (VIP), forskolin, and sodium nitroprusside were unaffected by L‐NNA pre‐incubation. Exposure to a 124 mM K+solution resulted in a biphasic relaxation of the preparations. This relaxation was not seen in preparations treated with scorpion venom (20/µg mr‐1) or L‐NNA (10‐4M). Instead, a contractile response to 124 mM K+solution was found. The results suggest that NANC responses to electrical stimulation of nerves in the human OGJ are mediated by a product generated from L‐arginine. Moreover, the inhibitory biphasic response to 124 mM K+is dependent on the release of this mediator, which seems capable of relaxing the muscle independently of changes in K+conductance.
Influences of stimulation frequency and temperature on interval‐force relationships in guinea‐pig papillary muscles
Authors: SPENCER C. I. , MÖRNER S. E. J. N. , NOBLE M. I. M. , SEED W. A.
Published: December 2008

Spencer, C. I., Mörner, S. E. J. N., Noble, M. I. M. & Seed, W. A. 1994. Influences of stimulation frequency and temperature on interval‐force relationships in guinea‐pig papillary muscles. Acta Physiol Scand 150, 11–20. Received 12 January 1993, accepted 25 August 1993. ISSN 0001–6772. Departments of Medicine and Academic Unit of Cardiovascular Medicine, Charing Cross and Westminster Medical School, London, UK and Department of Pharmacology, University of Lund, Sweden.

Relationships between contractile force and the preceding and pre‐preceding stimulation intervals were studied in papillary muscles by interposing variable test intervals during steady‐state pacing. The strength of test contractions increased exponentially to a maximum as the preceding (test) interval was lengthened. Contractility decreased as an exponential function of pre‐preceding interval. At 37 oC, the half times for these processes were unaffected by increasing the steady‐state frequency from 1 to 3 Hz. At 27 oC, the force increase with preceding interval was accelerated and the decay with pre‐preceding interval was retarded as the stimulation frequency was increased from 0.33 to 2 Hz.

The timecourses of force increase and decay were similar to each other during stimulation at an optimum frequency characteristic for the temperature. Cooling from 37 to 27 oC prolonged the half times for force increase and decay by factors of 4.5 and 3 respectively. The slope of the linear relationship between the force of the contraction pre‐preceded by the test interval and the immediately subsequent contraction (recirculation fraction) was also halved.

These results suggest that high stimulation frequency and low temperature uncouples cellular processes underlying the interval dependence of cardiac contractility. The temperature sensitivities are consistent with these processes being enzymatic. The reduced recirculation fraction provides a mechanism for the lowered threshold frequency for sustained mechanical alternans at 27 oC.
In vivo effects of endothelin‐2, endothelin‐3 and ETAreceptor blockade on arterial, venous and capillary functions in cat skeletal muscle
Authors: EKELUND U.
Published: December 2008

Ekelund, U. 1994.In vivoeffects of endothelin‐2, endothelin‐3 and ETAreceptor blockade on arterial, venous and capillary functions in cat skeletal muscle.Acta Physiol Scand150, 47–56. Received 31 March 1993, accepted 25 May 1993. ISSN 0001–6772. Department of Physiology & Biophysics, University of Lund, Sweden.

This study describes, in quantitative terms, the effects of endothelin‐2 and endothelin‐3 on vascular tone (resistance) in large‐bore arterial resistance vessels (> 25 /μm), small arterioles (< 25 μm) and the veins, as well as on capillary pressure and fluid exchange in cat gastrocnemius musclein vivo.Infusion of endothelin‐2 or endothelin‐3 (200–1600 ng kg‐1min‐1, i.a.) elicited an initial transient dilation, followed by a dose‐dependent, slowly developing constrictor response, being maintained after cessation of the infusion. At the dose of 400 ng kg‐1min‐1(n= 9), infused i.a. during 20 min, endothelin‐2 caused an average increase in total regional vascular resistance of 80%, and endothelin‐3 of 35%, and the site of constrictor action of both peptides was preferentially located to the small arterioles. Endothelin‐2 also constricted the veins and, hence, evoked a pronounced capacitance response, whereas endothelin‐3 was devoid of any venoconstrictor effect. This difference, via effects on the pre‐/post‐capillary resistance ratio, led to a more pronounced fall of capillary pressure in response to endothelin‐3 than to endothelin‐2. The new specific competitive ETAreceptor antagonist, FR 139317, abolished the vasoconstrictor response to both endothelin‐2 and endothelin‐3in vivo,whereas the preceding vasodilator responses were unaffected. These results, taken together with those of our previous analogous study of the effects of endothelin‐1, indicated that all three endothelins were approximately equally as effective in eliciting the transient dilator response in skeletal musclein vivo,whereas the order of vasoconstrictor activity was endothelin‐1 > endothelin‐2 > endothelin‐3. Due to an especially pronounced venoconstrictor activity of endothelin‐1, this peptide, in contrast to endothelin‐2 and ‐3, evoked a rise in capillary pressure, with a consequent net transcapillary fluid filtration and muscle tissue oedema formation. The results further indicated that the vasoconstrictor responses to all endothelins in skeletal muscle were mediated by the ETAreceptor, whereas the initial transient vasodilator responses seemed to be mediated by the ETBreceptor.
The contractile and electrophysiological effects of rolipram in guinea‐pig papillary muscles and isolated ventricular myocytes
Authors: MÖRNER S. E. J. N. , ARLOCK PER
Published: December 2008

Isometric force, action potentials and in voltage‐clamp 1st (second inward current) and its current voltage relation were recorded in papillary muscles from guinea‐pigs and from guinea‐pig isolated ventricular myocytes (35–37 oC, 0.5‐1 Hz). Rolipram (1–100 µM) had no significant effect on peak isometric twitch. The rate of rise of force and time to peak tension (TPT) was likewise unaffected. Time to half relaxation (THR) was increased in a dose‐dependent manner and at 30 µM THR was prolonged by 25.3 ± 6% (n= 10, P < 0.001). The effect of 30µM rolipram on isometric force was frequency dependent. At 0.25 Hz peak force was increased by 6.3 ± 3.1% (n= 7, P < 0.05). At 2 Hz rolipram exhibited a negative inotropic effect of 9.8 ± 3.3% (n= 5, P < 0.02). Action potential duration at 90% repolarization was prolonged by 13 ± 6 ms (n= 7, P < 0.05), and there was usually no effect on resting potential or action potential amplitude. Sometimes, however, a depressed plateau was recorded. Rolipram was without effect on I1st and its current‐voltage relations. Time to full mechanical restitution after a test interval was not changed but the shape of the restitution curve was altered. The restitution process was much slower in the presence of rolipram. Hence, peak force was lower at test intervals shorter than 800 ms. Likewise, the shape of the curve relating postextrasystolic potentiation to test interval was altered by rolipram. The interval required for maximum potentiation was increased by rolipram and did not significantly affect the recirculation fraction of activator calcium.
Reduced permselectivity in isolated perfused rat kidneys following small elevations of glomerular capillary pressure
Authors: JOHNSSON E. , RIPPE B. , HARALDSSON B.
Published: December 2008

A modified rat kidney preparation was used to explore how changes in hydrostatic pressure affect the permselective properties of the glomerular capillary bed. Th? maximally vasodilated kidneys of 18 rats were perfused with albumin solutions (16.7 g ‐1) at different flow rates and hence arterial pressures (PA). One kidney in each rat was exposed to pressure elevations with the other kidney serving as a control perfused at constant PA of about 100 mmHg. Both the vascular resistance to flow and the glomerular filtration rate (GFR 34.6 ± 2.9 ml min1 100 g_1) were similar in the two kidneys at equal PA and remained constant throughout the experiment. The ratio of albumin clearance over GFR (Θ) was initially around 0.4% at constant PA and gradually increased during 1.5 h to reach 0.7% at the end of the experiment. A direct increase of PA from 100 to 200 mmHg for 15 min resulted in a calculated increase of the effective glomerular filtration pressure gradient of 10–15 mmHg and in a two‐fold increase ofΘ when measured at an identical PA of 100 mmHg. Albumin clearance was almost fully normalized within 20 min similar to that observed in e.g. skeletal muscle. However, the glomerular capillary barrier seemed to be far more sensitive to elevations of hydrostatic pressure than other capillary walls which require capillary pressure increments of 60 mmHg in order to induce similar reversible changes in permeability. Therefore, we conclude that an elevated PG:c per se induces changes of glomerular permselectivity, which may have important pathophysiological implications during conditions of proteinuria.
Glucose kinetics during exercise in trained men
Authors: HARGREAVES M. , PROIETTO J.
Published: December 2008

Six trained men were studied to examine the relative increases in hepatic glucose output and peripheral glucose uptake during 40 min of exercise at 75%Vo2max. Rates of appearance (Ra) and disappearance (Rd) were measured using a primed, continuous intravenous infusion of D‐[3‐3H]glucose. Plasma glucose increased (P < 0.05) from 4.8 ± 0.2 mmol I‐1 at rest to 6.2 ± 0.5 mmol l‐1 after 40 min of exercise. Both Ra and Rd increased (P < 0.05) during exercise, however, during the early phase of exercise, Ra exceeded Rd (P < 0.05). Ra peaked at 42.0 ±3.2/tmol kgf1 min‐1 after approximately 15 min of exercise. In contrast, the highest Rd of 33.9 ± 4.3 μmol kg‐1 min‐1 was measured at the end of exercise. In additional experiments, five men were studied during 40 min of exercise at 70–75%Vo2max, 2 h after ingestion of the non‐selective β‐adrenergic antagonist timolol or a placebo capsule. Subjects were unable to complete the exercise bout following timolol, fatiguing after 28.0 ± 4.0 min (P < 0.05). The increase in blood glucose from 4.3 ±0.1 to 4.7 ± 0.3 mmol l‐1 (P < 0.05) following 20 min of exercise under control conditions was completely abolished by prior timolol ingestion (4.2 ± 0.2 to 4.1±0.2 mmol l‐1). These results demonstrate that during exercise at 75%Vo2max in trained men, hepatic glucose output is not always closely matched to peripheral muscle glucose uptake and may be subject to feed‐forward regulation. The abolition of the hyperglycaemia with non‐selective β‐adrenergic blockade implicates adrenaline in this response.
Ischaemic episodes of less than 5 minutes produce preconditioning but not stunning in the isolated rat heart
Authors: SCHJØTT J. , YNGE P. J. , HOLTEN T. , BRUROK H.
Published: December 2008

The aim of the present study was to examine whether ischaemic episodes of less than 5 min could induce preconditioning or stunning in the isolated rat heart. Hearts were subjected to total global ischaemia of 1, 2 and 4 min followed by 10 min of reperfusion before an 18‐min main ischaemic period and 30 min of reperfusion. The effects on physiology, purine metabolism and anaerobic glycolysis were compared with a control group subjected to the main ischaemia only. The brief ischaemic episodes did not produce stunning based on the recovery of left ventricular developed pressure (LVDP) and heart rate (HR) product during the first reperfusion. Preconditioning of 11–14% increased recovery of LVDP x HR during the second reperfusion was observed in the 1‐ and 4‐min group. In the 2‐min group a low repayment of flow debt during the first reperfusion was associated with a slightly reduced recovery of LVDP x HR compared to the other preconditioned groups during the second reperfusion. Only in the 4‐min group was preconditioning associated with fewer breakdown products of the purine nucleotide pool (adenosine) and anaerobic glycolysis (lactate) in both tissue and effluate after the main ischaemia. Preconditioning (reflected in recovery of function) could be produced with ischaemic episodes of less than 5 min that did not produce stunning. Thus, stunning is probably not the primary cause of preconditioning.
Sex differences in endocrine response to hyperthermia in sauna
Authors: JEŽOVÁ D. , KVETŇANSKÝ R. , VIGAŠ M.
Published: December 2008

Neuroendocrine response was investigated during and after a single 20 min bath in sauna (80 oC) in a group of 8 healthy men and 8 healthy women. In an additional group of 8 young men, the dynamics of plasma ACTH and Cortisol levels were studied during a 30 min sauna exposure (90 oC). This dynamic study showed a biphasic response of plasma Cortisol which decreased during the initial phase of sauna bath (15 min) and increased thereafter, reaching its maximum 15 min after the end of bathing. Maximal increase in plasma ACTH levels occurred 15 min earlier. In the first sauna exposed group the increase in body temperature was the same (about 2 oC) in both sexes. Nevertheless, the elevation in plasma ACTH concentration was significantly more pronounced in women than in men. In the plasma collected at the end of sauna bath inside the sauna room, a significant rise in both adrenaline and noradrenaline levels was found. Though the catecholamine responses were similar in both groups, the increase in heart rate during sauna bath was significantly higher in women. Sauna–induced prolactin release was also more pronounced in women compared with men. Thus hyperthermia induced by sauna exposure resulted in a more pronounced neuroendocrine activation in women compared with men. Moreover, it is evident that repeated blood sampling is necessary to reveal the sauna–induced activation of some hormonal systems.
The transition between walking and running in humans: metabolic and mechanical aspects at different gradients
Authors: MINETTI A. E. , ARDIGO L. P. , SAIBENE F.
Published: December 2008

Five subjects walked and ran at overlapping speeds and different gradients on a motorized treadmill. At each gradient the speed was obtained at which walking and running have the same metabolic cost (Sm) and the speed of spontaneous (Ss) transition between the two gaits was measured. Ss was found to be statistically lower than Sm at all gradients, the difference being in the range of 0.5–0.9 km h‐1. The motion analysis of walking reveals that at all gradients and at increasing speed: (1) the percentage of recovery, an index of mechanical energy saving related to the pendulum–like characteristic of walking, decreases; (2) the lower limb spread reaches a limit in walking; and consequently (3) both the stride frequency and the internal mechanical work, due to limb acceleration in relation to the body centre of mass, increase much more in walking than in running. Switching to a run, although implying a higher frequency, makes the internal work decrease as a result of the lower limb spread. In this paper several influences, such as the ‘ratings of perceived exertion’ (RPE), on the choice of beginning to run when it is more economical to walk, are discussed. A tentative hypothesis on the determinants of Ss, which is emphasized to be a speed which has to be studied in detail but is generally avoided in locomotion, is based on a comfort criterion from peripheric afferences and is reflected by the fact that at Ss a running stride costs as much as a walking stride. A preliminary measure of the subjects' behaviour during spontaneous overground locomotion, where the progression speed can be changed freely, reveals that the running speed immediately following gait transition is approximately 2 km h‐1 higher than the ‘last’ walking speed, supporting the hypothesis of metabolic energy minimization.
The inotropic mechanism of the phosphodiesterase inhibitor OPC 3911 alone and in combination with rolipram, studied in papillary muscles of ferret and guinea–pig and isolated myocytes of guinea–pig ventricular muscle
Authors: MÖRNER S. E. J. N. , ARLOCK P. , LINDGREN S.
Published: December 2008

OPC 3911 is a potent inhibitor and PDE III is a specific inhibitor in cardiac muscle. The effects of the drug alone and in combination with the non–inotropic PDE IV inhibitor rolipram were analysed using hearts from guinea–pigs and ferrets. OPC 3911 had an EC50 value of 0.1μM. At 0.1 fiM peak force was increased by 50.7 ± 7.6% (n = 6, P< 0.001), time to peak tension (TPT) reduced by 18,7±5.6% (n = 6, P < 0.05). Time to half relaxation (THR) was prolonged by 19±4.2% (n= 6, P < 0.001). After addition of rolipram (30 μM) there was a potentiation of peak force at all concentrations of OPC 3911. At 0.1 μM OPC rolipram increased peak force by 82.8±8.9% (n= 6, P < 0.001), reduced TPT by 73 ± 6% (n = 6, P < 0.005) and increased THR by 27±5% (P<0.01). OPC 3911 shortened action potential duration (APD) at 50% repolarization by 5.3 ±2.5% (n= 6, P < 0.05). Addition of rolipram prolonged APD by 3.7 ± 2.5% (n = 6, P < 0.05). Second inward current (I8l) was increased at 3μM OPC 3911 by 46 ± 6% (n = 6, P< 0.05). The combination of OPC 3911 and rolipram intensified the I8l to 101 ± 5% (n= 3). Rolipram slowed the rate of restitution and the onset of restitution was prolonged. Relative maximum post–extrasystolic potentiation was reduced in the presence of OPC 3911 from 67 ± 5% to 45 ±6%. Adding rolipram caused potentiation of 55 ± 6%. OPC 3911 increased the recirculation fraction of activator calcium from 0.36 to 0.42 (n = 10, P < 0.05). After addition of rolipram the recirculation fraction was 0.41 ± 0.04 (n =10, P < 0.05). The results suggest that rolipram exerts its potentiating effect on OPC 3911 via an increased Isl.
Wall mechanics of the rat bladder. I. Hydrodynamic studies in the time domain
Authors: ANDERSSON S. , KRONSTRÖM A. , TEIEN D.
Published: December 2008

The hydrodynamic properties of the rat bladder in the collection phase were examined by slow continuous and very fast stepwise cystometry in nine rats. In vivo, the fast volume steps induced a reproducible detrusor contraction (type A) which remained after spinal anaesthesia and anticholinergic treatment, but ceased post‐mortally within I h. No significant effect of anticholinergic treatment was found on bladder stiffness. The stiffness and relaxation time of the bladder wall increased markedly at large distension. At small and moderate distension, however, the compliances evaluated from continuous and stepwise cystometry were nearly the same, and a linear elastic model of the bladder was applicable. We consider that the rat bladder will be a useful experimental model in further research on viscoelasticity and instability of the bladder wall.
Serial measurements of plasma renin activity, aldosterone and cortisol during percutaneous transluminal angiaplasty of the renal artery in man
Authors: HÄGG A. , LORELIUS L.‐E. , MÖRLIN C. , WIDE L.
Published: December 2008

Fifteen patients (eight men, seven women) with hypertension and renal artery stenosis underwent dilation of the stenosis by percutaneous transluminal renal angioplasty (PTRA). During and shortly after this treatment the effects on the renin‐angio‐tensin‐aldosterone system and blood pressure were studied. Plasma renin activity (PRA) was measured in peripheral blood and in renal venous blood during the PTRA. PRA increased in peripheral blood during PTRA as a result of an immediate significant rise in renal venous plasma renin activity by 132 ± 134% (P < 0.01) on the dilated side. PRA in the contralateral renal vein was close to that in peripheral blood. Within 10 min after PTRA i:here was a significant increase in serum aldosterone from 439 ± 343 to 774 ± 635 pmol l‐1 (P < 0.025), while serum cortisol remained unchanged. The aldosterone increase was most probably mediated by angiotensin II. Systolic and diastolic blood pressures were unchanged during PTRA in spite of renin and aldosterone increases, suggesting that antihypertensive factors counteract the pressor effects of a physiologically relevant increase in PRA.
Renal sympathetic nerve activity during morphine abstinence in sino‐aortic baroreceptor‐denervated rats
Authors: DELLE M. , RICKSTEN S. ‐E. , THORÉN P.
Published: December 2008

This study was undertaken to investigate the influence of the arterial baroreceptors on the response of renal sympathetic nerve activity (rSNA) during naloxone‐precipitated morphine abstinence in rats. In chronically baroreceptor‐denervated, morphine‐dependent rats, rSNA, mean arterial pressure (MAP) and heart rate (HR) were studied before and after repeated i.v. bolus doses of naloxone (0.005–5 mg kg‐1), during chloralose anaesthesia or in the conscious state.

In the anaesthetized animals, naloxone doses of 0.05–5 mg kg‐1caused a pronounced inhibition of rSNA, reaching a level 61 % below pre‐naloxone activity. This was accompanied by increases in MAP and HR. In the conscious rats, the lower doses of naloxone elicired an initial state of increased somatomotor activity. This was paralleled by slight increases in rSNA and MAP. After 4–5 min, the behavioural excitation faded and was replaced by lethargy. The rats exhibited still signs of withdrawal in the form of piloerection, chromodacryorrhoea and defaecations. Concomitantly, rSNA returned towards the pre‐naloxone level, while MAP showed a sustained increase. The higher naloxone doses exacerbated the hypertension without any further changes in rSNA or in behaviour.

We conclutle that the influence of the baroreceptors is of minor significance for the inhibition of rSNA during naloxone‐precipitated abstinence in anaesthetized rats. In conscious, intact rats, however, the baroreceptors seem to contribute to rSNA inhibition since no significance decrease of rSNA occurred in baroreceptor‐denervated rats in the present study. This is in contrast to our previous finding of a marked inhibition of rSNA in rats with intact baroreceptors.
Increase in capillary blood flow and relative haematocrit in rabbit skeletal muscle following acute normovolaemic anaemia
Authors: LINDBOM L. , MIRHASHEMI S. , INTAGLIETTA M. , ARFORS K.‐E.
Published: December 2008

The effect of acute normovolaemic haemodilution on microvascular red blood cell flow was studied by intravital microscopy in the tenuissimus muscle of the rabbit. Blood was substituted isovolaemically with equal volumes of a 6% solution of dextran 70 (MW 70,000). The systemic haematocrit (Hsys) decreased from 36 ± 4% (mean ± SD) to 17 ± 2%. Following haemodilution capillary haematocrit (Hcap), as measured by video densitometric methods, decreased by 20 ± 9%. The reduction of Hcap was significantly smaller than that of Hsys and Hcap normalized with respect to H sys increased from 0.39 ± 0.07 in the control situation to 0.62 ± 0.18 after haemodilution. Red blood cell velocity (vrbcr) increased by 45 ± 20 % and compensated for the decrease in Hcap in such a way that the red blood cell flux, calculated from vrbc and Hcap remained unchanged. Measurements of volume flow in the feeding arterioles in the muscle revealed a fractional redistribution of blood flow in favour of the muscle capillaries following haemodilution at the expense of vessels in adjacent connective tissue supplied by the same arterioles. This fractional flow redistribution was likely the basis for the relative increase in capillary haematocrit seen after haemodilution. The present data demonstrate that an acute reduction of the systemic haematocrit is compensated for in an active regulating vascular bed by a proportionally smaller decrease in capillary haematocrit and by an increased capillary red cell velocity. Microvascular haematocrit was found not to be a constant fraction of the systemic value, which supports the view of capillary haematocrit as a ‘controlled’ physiological variable.
Motor responses elicited by local electrical stimulation of the distal colon in the anaesthetized rat
Authors: NIKLASSON L.‐G. , GUSTAFSSON B. I. , NORDGREN S. , FASTH S. , HULTEN L. , DELBRO D.
Published: December 2008

A method to study electrically induced distal colonic motility in the rat in vivo is reported. The animals were anaesthetized with methohexital and chloralose and were artificially ventilated. Motility of a segment (2 cm) of the distal colon was monitored as volume changes of an intraluminal balloon, introduced via the anus. Local electrical stimulation of the wall of the segment was achieved by means of a bipolar electrode folded around the gut. Stimulations produced reproducible contractile responses in a frequency dependent fashion. Stimulation characteristics resembled those of other autonomic neuro‐effector systems. The adrenergic neuron‐blocker, guanethidine, significantly lowered colonic tone, but had no other effects on spontaneous or electrically induced motility. Atropine significantly lowered colonic tone. After the administration of this compound the electrically induced contractions were significantly smaller with a shorter duration and, furthermore, appeared upon the cessation of stimulation (off) or ‘rebound’ contraction). Following the administration of tetrodotoxin (TTX, given close i.a. via a cannula with its tip in distal aorta) basal colonic tone and the number of spontaneously occurring contractions increased. The amplitude and duration of the electrically induced responses were significantly attenuated and, furthermore, appeared as ‘rebound’ contractions which were preceded by a relaxation. Such TTX‐resistant responses may be myogenic, but a neurogenic origin cannot he excluded. The present study showed that local electrical stimulation of the distal colon elicits cholinergic contractions, but also atropine‐ and TTX‐resistant motor responses.
Influence of herring (Clupea harengus) and herring fractions on metabolic status in rats fed a high energy diet
Authors: Lindqvist H. , Sandberg A.‐S. , Undeland I. , Stener‐Victorin E. , Larsson B. M. , Sannaveerappa T. , Lönn M. , Holmäng A.
Published: December 2008

Aim:  Few dietary studies have looked beyond fish oil to explain the beneficial metabolic effects of a fish‐containing diet. Our aim was to study whether addition of herring, or sub‐fractions of herring, could counteract negative metabolic effects known to be induced by a high‐fat, high‐sugar diet.

Methods:  Rats were given six different diets: standard pellets; high energy diet with chicken mince (HiE control); high energy diet with herring mince (HiE herring); and high energy diet with chicken mince and either herring oil (HiE herring oil), herring press juice, PJ (HiE PJ) or herring low molecular weight PJ (HiE LMW‐PJ). Factors associated with the metabolic syndrome were measured.

Results:  There were no differences in energy intake or body weight between the groups, but animals fed high energy diets had a higher body fat content compared with the pellet group, although not statistically significant in all groups. Mesenteric adipocyte size was smaller in the HiE herring oil group compared with the HiE control. Glucose clamp studies showed that, compared with the pellet group, the HiE control and HiE herring diets, but not the HiE herring oil diet, induced insulin resistance. Addition of herring or herring oil to the high energy diet decreased total cholesterol levels, triacylglycerols and the atherogenic index compared with the HiE control group.

Conclusions:  The results suggest that addition of herring or herring oil counteracts negative effects on blood lipids induced by a high energy diet. The lipid component of herring thus seems to be responsible for these beneficial effects.
Changes in satiety hormones and expression of genes involved in glucose and lipid metabolism in rats weaned onto diets high in fibre or protein reflect susceptibility to increased fat mass in adulthood
Authors: Maurer Alannah D. , Chen Qixuan , McPherson Christine , Reimer Raylene A.
Published: December 2008

Risk of developing obesity and diabetes may be influenced by the nutritional environment early in life. We examined the effects of high fibre or protein diets on satiety hormones and genes involved in glucose and lipid metabolism during postnatal development and on adult fat mass. At 21 days of age, Wistar rat pups were weaned onto control (C), high fibre (HF) or high protein (HP) diet. Tissue and blood were collected at 7, 14, 21, 28 and 35 days after birth. A second group of rats consumed the weaning diets until 4 months when they were switched to a high fat–high sugar diet for 6 weeks, after which body and fat mass and plasma glucose were determined. In young rats, HF diet increased plasma glucagon‐like peptide (GLP‐1) compared to C and HP and decreased leptin compared to C at postnatal days 28 and 35. Hepatic fatty acid synthase mRNA was down‐regulated by HF and HP compared to C at days 28 and 35. In brown adipose tissue, HF increased uncoupling protein‐3 mRNA whereas HP increased mRNA of the inflammatory cytokine interleukin‐6. Body weight, fat mass and glycaemia in adult males and fat mass in females were greater after the high fat challenge in rats that consumed the HP diet from weaning. Increasing fibre or protein in postnatal diets causes rapid change in satiety hormone secretion and genes involved in glucose and lipid metabolism which appear to influence fat mass and glycaemia in adulthood, high protein being associated with increased susceptibility to obesity.
The effect of a prepulse stimulus on the EMG rebound following the cutaneous silent period
Authors: Kumru H. , Opisso E. , Valls‐Solé J. , Kofler M.
Published: December 2008

The cutaneous silent period (CSP) is a spinal inhibitory reflex mediated by Aδ fibres. The postinhibitory rebound of electromyographic (EMG) activity following the CSP has been mainly attributed to resynchronization of motoneurons, but the possibility of startle reflex activity contributing to the EMG burst has also been suggested. Several types of reflexes may be suppressed by a preceding weak stimulus – a phenomenon called prepulse inhibition (PPI). Our aim was to study whether PPI would diminish the EMG rebound, thereby providing further evidence for excitatory reflex activity contained within the postinhibitory EMG rebound following the CSP. Ten healthy subjects underwent CSP testing following noxious digit II stimulation in two conditions, with and without a prepulse applied to digit III. Rectified surface EMG recordings were obtained from right orbicularis oculi, sternocleidomastoid and thenar muscles of the dominant hand during thumb abduction with 25% of maximum force. The area of the EMG rebound and the EMG reflex responses in orbicularis oculi and sternocleidomastoid were significantly smaller in recordings where a prepulse stimulus was applied 100 ms before the stimulus as compared to control responses without prepulse. CSP onset and end latency, CSP duration, and the degree of EMG suppression were not influenced. Prepulses significantly reduced subjective discomfort as based on visual analog scale scores. Inhibition of the EMG rebound by prepulse stimulation supports the hypothesis that the excitatory EMG activity following the CSP contains not only resynchronization of motoneuronal firing, but also an excitatory reflex component. The most probable type of reflex seems to be a somatosensory startle reflex, a defence reaction which is generated in structures located in the caudal brainstem following an unexpected intense stimulus. Reduction of the discomfort associated with high‐intensity electrical fingertip stimulation by a prepulse without affecting CSP parameters underlines the utility of PPI in the context of CSP testing.
In Vitro Activities of Various Antifungal Drugs against
Aspergillus terreus
: Global Assessment Using the Methodology of the European Committee on Antimicrobial Susceptibility Testing
Authors: Lass-Flörl Cornelia , Alastruey-Izquierdo Ana , Cuenca-Estrella Manuel , Perkhofer Susanne , Rodriguez-Tudela Juan Luis
Published: December 2008

This study presents in vitro susceptibility data for clinical (
n
= 48) and environmental (
n
= 31) isolates of
Aspergillus terreus
against nine antifungal agents. The methodology of the European Committee on Antimicrobial Susceptibility Testing was applied. Posaconazole and anidulafungin had the lowest and amphotericin B the highest MICs. No differences in susceptibility patterns were observed between environmental and clinical isolates.
Prevalence of Sulfonamide Resistance Genes in Bacterial Isolates from Manured Agricultural Soils and Pig Slurry in the United Kingdom
Authors: Byrne-Bailey K. G. , Gaze W. H. , Kay P. , Boxall A. B. A. , Hawkey P. M. , Wellington E. M. H.
Published: December 2008

The prevalences of three sulfonamide resistance genes,
sul1
,
sul2
, and
sul3
and sulfachloropyridazine (SCP) resistance were determined in bacteria isolated from manured agricultural clay soils and slurry samples in the United Kingdom over a 2-year period. Slurry from tylosin-fed pigs amended with SCP and oxytetracycline was used for manuring. Isolates positive for
sul
genes were further screened for the presence of class 1 and 2 integrons. Phenotypic resistance to SCP was significantly higher in isolates from pig slurry and postapplication soil than in those from preapplication soil. Of 531 isolates, 23% carried
sul1
, 18%
sul2
, and 9%
sul3
only. Two percent of isolates contained all three
sul
genes. Class 1 and class 2 integrons were identified in 5% and 11.7%, respectively, of
sul
-positive isolates. In previous reports,
sul1
was linked to class 1 integrons, but in this study only 8% of
sul1
-positive isolates carried the
intI1
gene. Sulfonamide-resistant pathogens, including
Shigella flexneri
,
Aerococcus
spp., and
Acinetobacter baumannii
, were identified in slurry-amended soil and soil leachate, suggesting a potential environmental reservoir. Sulfonamide resistance in
Psychrobacter
,
Enterococcus
, and
Bacillus
spp. is reported for the first time, and this study also provides the first description of the genotypes
sul1
,
sul2
, and
sul3
outside the
Enterobacteriaceae
and in the soil environment.
Prevalence of Plasmid-Mediated Quinolone Resistance Determinants over a 9-Year Period
Authors: Kim Hong Bin , Park Chi Hye , Kim Chung Jong , Kim Eui-Chong , Jacoby George A. , Hooper David C.
Published: December 2008

Recently, several plasmid-mediated quinolone resistance (PMQR) genes conferring low levels of quinolone resistance have been discovered. To evaluate the temporal change in the prevalence of PMQR genes over a decade in a tertiary hospital in the Republic of Korea, we selected every fifth isolate of
Escherichia coli
and
Klebsiella pneumoniae
and every third isolate of
Enterobacter cloacae
between 1998 and 2001 and between 2005 and 2006 from a collection of blood isolates. Six PMQR genes [
qnrA
,
qnrB
,
qnrC
,
qnrS
,
aac(6′)-Ib-cr
, and
qepA
] were screened by multiplex PCR and then confirmed by direct sequencing, and the
aac(6′)-Ib
-positive PCR products were digested with BtsCI to identify the
aac(6′)-Ib-cr
variant. Of 461 isolates, 37 (8%) had one of the six PMQR genes; 13 (5%) of 261
E. coli
strains, 13 (10%) of 135
K. pneumoniae
strains, and 11 (17%) of 65
E. cloacae
strains.
qnrB
was the most common PMQR gene and was found as early as 1998, whereas
qnrS
,
aac(6′)-Ib
-
cr
, and
qepA
emerged after 2000. None of the isolates carried
qnrA
or
qnrC
. Ciprofloxacin resistance increased over time (
P
< 0.001), and the overall prevalence of PMQR genes tended to increase (
P
= 0.20). PMQR-positive isolates had significantly higher ciprofloxacin resistance and multidrug resistance rates (
P
= 0.005 and
P
< 0.001, respectively). The increasing frequency of ciprofloxacin resistance in
Enterobacteriaceae
was associated with an increasing prevalence of PMQR genes, and this change involved an increase in the diversity of the PMQR genes and also an increase in the prevalence of the mutations in
gyrA
,
parC
, or both in PMQR-positive strains but not PMQR-negative strains.
Novel Staphylococcal Cassette Chromosome
mec
Type, Tentatively Designated Type VIII, Harboring Class A
mec
and Type 4
ccr
Gene Complexes in a Canadian Epidemic Strain of Methicillin-Resistant
Staphylococcus aureus
Authors: Zhang Kunyan , McClure Jo-Ann , Elsayed Sameer , Conly John M.
Published: December 2008

Staphylococcal cassette chromosome
mec
(SCC
mec
) is a mobile genetic element characterized by flanking terminal direct and, in most cases, inverted repeat sequences, the
mec
and
ccr
gene complexes, and their surrounding DNA regions. Unique combinations of the
mec
and
ccr
gene complexes generate various SCC
mec
types. Six SCC
mec
types have been reported to date. We describe here a novel SCC
mec
type identified in a Canadian methicillin-resistant
Staphylococcus aureus
(MRSA) epidemic strain. MRSA clinical isolates were screened for known SCC
mec
types by multiplex and conventional PCR methods. Three phenotypically and genotypically identical MRSA clinical isolates with a pulsotype identical to CMRSA9 were identified locally and found to be nontypeable by available SCC
mec
typing schemes. Complete sequencing of the SCC
mec
element revealed a nucleotide fragment of 32,168 bp integrated at an identical chromosomal integration site (
att
B
scc
) at the 3′ end of the
orfX
gene. The nucleotide sequences at the chromosome-SCC
mec
junction regions were typical of other SCC
mec
types, but the element harbored a unique combination of class A
mec
and type 4
ccr
gene complexes. Sequence recombination analysis suggested that this unique SCC
mec
type may be derived from homologous recombination between the previously described SCC
RP62A
of
S. epidermidis
strain RP62A and SCC composite island of
S. epidermidis
ATCC 12228, respectively, or via recombination of other staphylococcal strains that carry the same or similar mobile cassettes. We identified a previously undescribed type of SCC
mec
from isolate C10682, tentatively designated type VIII, and we provide compelling evidence supporting the ability of SCC elements to transfer horizontally or undergo recombination to generate new SCC
mec
types.
TheYersinia pestisAil Protein Mediates Binding and Yop Delivery to Host Cells Required for Plague Virulence
Authors: Felek Suleyman , Krukonis Eric S.
Published: December 2008

Although adhesion to host cells is a critical step in the delivery of cytotoxic Yop proteins byYersinia pestis, the mechanism has not been defined. To identify adhesins critical for Yop delivery, we initiated two transposon mutagenesis screens using themarinertransposon. To avoid redundant cell binding activities, we initiated the screen with a strain deleted for two known adhesins, pH 6 antigen and the autotransporter, YapC, as well as the Caf1 capsule, which is known to obscure some adhesins. The mutants that emerged contained insertions within theail(attachment and invasion locus) gene ofY. pestis. A reconstructed mutant with a single deletion in theaillocus (y1324) was severely defective for delivery of Yops to HEp-2 human epithelial cells and significantly defective for delivery of Yops to THP-1 human monocytes. Specifically, the Yop delivery defect was apparent when cell rounding and translocation of an ELK-tagged YopE derivative into host cells were monitored. Although theailmutant showed only a modest decrease in cell binding capacity in vitro, the KIM5 Δailmutant exhibited a >3,000-fold-increased 50% lethal dose in mice. Mice infected with the Δailmutant also had 1,000-fold fewer bacteria in their spleens, livers, and lungs 3 days after infection than did those infected with the parental strain, KIM5. Thus, the Ail protein is critical for bothY. pestistype III secretion in vitro and infection in mice.
Active and Passive Immunizations withBordetellaColonization Factor A Protect Mice against Respiratory Challenge withBordetella bronchiseptica
Authors: Sukumar Neelima , Love Cheraton F. , Conover Matt S. , Kock Nancy D. , Dubey Purnima , Deora Rajendar
Published: December 2008

Bordetella colonizationfactorA(BcfA) is an outer membrane immunogenic protein, which is critical for efficient colonization of the murine respiratory tract. These properties of BcfA prompted us to examine its utility in inducing a protective immune response againstBordetella bronchisepticain a mouse model of intranasal infection. Mice vaccinated with BcfA demonstrated reduced pathology in the lungs and harbored lower bacterial burdens in the respiratory tract. Immunization with BcfA led to the generation of BcfA-specific antibodies in both the sera and lungs, and passive immunization led to the reduction ofB. bronchisepticain the tracheas and lungs. These results suggest that protection after immunization with BcfA is mediated in part by antibodies against BcfA. To further investigate the mechanism of BcfA-induced immune clearance, we examined the role of neutrophils and macrophages. Our results demonstrate that neutrophils are critical for anti-BcfA antibody-mediated clearance and that opsonization with anti-BcfA serum enhances phagocytosis ofB. bronchisepticaby murine macrophages. We show that immunization with BcfA results in the production of gamma interferon and subclasses of immunoglobulin G antibodies that are consistent with the induction of a Th1-type immune response. In combination, our findings suggest that the mechanism of BcfA-mediated immunity involves humoral and cellular responses. Expression of BcfA is conserved among multiple clinical isolates ofB. bronchiseptica. Our results demonstrate the striking protective efficacy of BcfA-mediated immunization, thereby highlighting its utility as a potential vaccine candidate. These results also provide a model for the development of cell-free vaccines againstB. bronchiseptica.
Mushroom crops in relation to weather in the southwestern Yukon
Authors: Krebs C. J. , Carrier Patrick , Boutin S. , Boonstra R. , Hofer Elizabeth
Published: December 2008

Epigeous mushroom production in the boreal forest ecosystem varies dramatically from year to year. We tested the hypothesis that the aboveground production of epigeous mushrooms in the Kluane region, Yukon, could be predicted by summer rainfall. There is a single crop in this part of the boreal zone with maximum production during the first 2 weeks of August. We measured standing crops from 1993 to 2007 at 13 areas along 210 km of the Alaska Highway and Haines Road in the southwestern Yukon. Aboveground mushroom crops averaged 24 kg/ha wet weight but varied from 0.0 to 117 kg/ha over the 15 years of study, with a coefficient of variation among years of 143%. Epigeous mushroom production could be predicted from June rainfall of the current year and May rainfall of the year previous with R2 = 0.85. Part of the lack of a perfect fit to rainfall was due to the constraint that years of high mushroom crops could not be followed by another high year, no matter what the rainfall pattern. We were not able to identify the species of mushrooms in this study but we confirm from natural history observations that mushrooms are a critical food for several of the small mammal species in the Yukon boreal forest.