| 1. |
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| 2. |
- Asgeirsson, Daniel, et al.
(författare)
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Glomerular sieving of three neutral polysaccharides and bikunin in rat. - Effects of molecular size and conformation.
- 2007
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 191:3, s. 237-246
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Polysaccharides and many other non-protein polymers generally have a more open, flexible and asymmetrical structure compared with globular proteins. For a given molecular weight (MW), the Stokes–Einstein radius (ae) of the following polymers increases in the order: Ficoll < dextran ≤ pullulan < polyethylene oxide (PEO). We have tested the hypothesis that such an increase in 'molecular extension' will increase the molecule's glomerular permeability. Thus, we investigated the glomerular sieving coefficients (θ) of the mentioned polymers and of the negatively charged and extended protein bikunin. Methods: In anaesthetized Wistar rats, glomerular sieving curves were generated for each FITC-labelled polymer from their respective concentration in urine and plasma, determined by size exclusion chromatography. The θ for bikunin was measured using a tissue uptake technique. Results: For a molecule of ae = 55 Å (cf. IgG), θ increased in the order: Ficoll (0.00035 ± 0.000013) < dextran (0.022 ± 0.0029) < pullulan (0.033 ± 0.0024) < PEO (0.12 ± 0.0055). For ae = 36 Å (cf. albumin) the order was: Ficoll (0.076 ± 0.0061) < dextran (0.45 ± 0.037) = pullulan (0.45 ± 0.021) < PEO (0.65 ± 0.0076). θ for bikunin (0.089 ± 0.0045) was 150 times higher than that of albumin, having an equivalent ae and net negative charge. Conclusion: From these results it is concluded that for flexible and asymmetric macromolecules, their degree of glomerular hyperpermeability is proportional to their degree of 'molecular extension'. Thus, compared with globular proteins, the polysaccharides investigated, including Ficoll, were found to be hyperpermeable across the glomerular filter in vivo.
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| 3. |
- Asgeirsson, Daniel, et al.
(författare)
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Similitude of permeabilities for Ficoll, pullulan, charge-modified albumin and native albumin across the rat peritoneal membrane.
- 2009
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 196:4, s. 427-433
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Aim: Compared to neutral globular proteins, neutral polysaccharides, such as dextran, pullulan and Ficoll, appear hyperpermeable across the glomerular filtration barrier. This has been attributed to an increased flexibility and/or asymmetry of polysaccharides. The present study investigates whether polysaccharides are hyperpermeable also across the continuous capillaries in the rat peritoneum. Methods: In anesthetized Wistar rats, FITC-Ficoll or FITC-pullulan together with (125)I-human serum albumin (RISA) or neutralized (125)I-bovine serum albumin (nBSA) were given intravenously, after which peritoneal dialysis using conventional peritoneal dialysis fluid (Gambrosol 1.5%) was performed for 120 min. Concentrations of FITC-polysaccharides and radioactive albumin species in plasma and dialysis fluid were analyzed with high performance size exclusion chromatography and a gamma counter, respectively. Transperitoneal clearance values were calculated for polysaccharides in the molecular radius range 36-150 A, and for RISA and nBSA. Results: Ficoll and pullulan showed more or less identical permeabilities, compared to RISA and nBSA, across the peritoneal membrane. Although RISA-clearance, 5.50+/-0.28 (muL/min; +/-SEM), tended to be lower than the clearances of Ficoll(36A) (6.55+/-0.25), pullulan(36A) (6.08+/-0.22) and nBSA (6.56+/-0.23), the difference was not statistically significant. This is in contrast to the hyperpermeability exhibited by polysaccharides across the glomerular filtration barrier and also contrasts with the charge selectivity of the latter. Conclusion: The phenomenon of molecular flexibility is more important for a macromolecule's permeability through the glomerular filter than across the continuous peritoneal capillary endothelium. Furthermore, it seems that charge plays a subordinate role in the steady-state transport across the combined peritoneal capillary-interstitial barrier.
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| 4. |
- Barg, Sebastian, 1969-, et al.
(författare)
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Compensatory endocytosis in chromaffin cells
- 2008
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 192:2, s. 195-201
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Forskningsöversikt (refereegranskat)abstract
- Exocytosis occurs via fusion of secretory granules with the cell membrane, whereupon the granule content is at least partially released and the granule membrane is temporarily added to the plasma membrane. Exocytosis is balanced by compensatory endocytosis to achieve net equilibrium of the cell surface area and to recycle and redistribute components of the exocytosis machinery. The underlying molecular mechanisms remain a matter of debate. In this review, we summarize and discuss recent progress in the understanding of compensatory endocytosis, with the focus on chromaffin cells as a useful model for studying mechanisms of regulated secretion.
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| 5. |
- Cao, Lei, et al.
(författare)
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Secondhand cigarette smoke exposure causes upregulation of cerebrovascular 5-HT(1B) receptors via the Raf/ERK/MAPK pathway in rats.
- 2013
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1716 .- 1748-1708. ; 207:1, s. 183-193
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Cigarette smoke exposure increases the risk of stroke. Upregulation of 5-hydroxytryptamine 1B (5-HT(1B) ) receptors is associated with the pathogenesis of cerebral ischemia. The present study examined the hypothesis that the expression of 5-HT(1B) receptors is altered in brain vessels after secondhand smoke (SHS) exposure. METHODS: Rats were exposed to SHS in vivo for 200 min daily for 8 weeks. The contractile responses of isolated cerebral arteries were studies by a sensitive myograph. The mRNA and protein expression for 5-HT(1B) receptors were examined by real-time PCR, Western blot and immunofluorescence, respectively. In addition, the phosphorylation of Raf/extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinases (MAPK) pathway was evaluated. RESULTS: The results showed that SHS exposure shifted the 5-HT(1B) receptor-mediated concentration-contraction curve toward the left with a markedly increased maximum contraction. Furthermore, there were significant elevations in mRNA level and protein expression of 5-HT(1B) receptors in SHS-exposed rats. Immunostaining revealed that the 5-HT(1B) receptors were localized to the smooth muscle cells of cerebral arteries. SHS was also found to induce the phosphorylation of Raf-1 and ERK1/2 proteins. The administration of a Raf-1 inhibitor GW5074 attenuated the 5-HT(1B) receptor upregulation. CONCLUSION: SHS exposure upregulates cerebrovascular 5-HT(1B) receptors in rats. The receptor upregulation is associated with Raf/ERK/MAPK activation. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.
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| 6. |
- Lindqvist, Helen, 1977, et al.
(författare)
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Influence of herring (Clupea harengus) and herring fractions on metabolic status in rats fed a high energy diet.
- 2009
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Ingår i: Acta physiologica (Oxford, England). - : Wiley. - 1748-1716 .- 1748-1708. ; 196:3, s. 303-14
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Lundborg, Göran, et al.
(författare)
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Hand function after nerve repair.
- 2007
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 189:2, s. 207-217
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of injuries to major nerve trunks in the hand and upper extremity remains a major and challenging reconstructive problem. Such injuries may cause long-lasting disabilities in terms of lost fine sensory and motor functions. Nowadays there is no surgical repair technique that can ensure recovery of tactile discrimination in the hand of an adult patient following nerve repair while very young individuals usually regain a complete recovery of functional sensibility. Post-traumatic nerve regeneration is a complex biological process where the outcome depends on multiple biological and environmental factors such as survival of nerve cells, axonal regeneration rate, extent of axonal misdirection, type of injury, type of nerve, level of the lesion, age of the patient and compliance to training. A major problem is the cortical functional reorganization of hand representation which occurs as a result of axonal misdirection. Although protective sensibility usually occurs following nerve repair, tactile discriminative functions seldom recover - a direct result of cortical remapping. Sensory re-education programmes are routinely applied to facilitate understanding of the new sensory patterns provided by the hand. New trends in hand rehabilitation focus on modulation of central nervous processes rather than peripheral factors. Principles are being evolved to maintain the cortical hand representation by using the brain capacity for visuo-tactile and audio-tactile interaction for the initial phase following nerve injury and repair (phase 1). After the start of the re-innervation of the hand (phase 2), selective de-afferentation, such as cutaneous anaesthesia of the forearm of the injured hand, allows expansion of the nerve-injured cortical hand representation, thereby enhancing the effects of sensory relearning. Recent data support the view that training protocols specifically addressing the relearning process substantially increase the possibilities for improved functional outcome after nerve repair.
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| 8. |
- Meidute, Sandra, et al.
(författare)
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Imidazoline-induced amplification of glucose- and carbachol-stimulated insulin release includes a marked suppression of islet NO generation in the mouse.
- 2009
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 195:3, s. 375-383
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The role of islet nitric oxide (NO) production in insulin releasing mechanisms is unclear. We examined whether the beneficial effects of the imidazoline derivative RX 871024 (RX) on beta-cell function might be related to perturbations of islet NO production. Methods: Experiments were performed with isolated islets or intact mice challenged with glucose or carbachol with or without RX treatment. Insulin was determined with radioimmunoassay, NO generation with high-performance liquid chromatography and expression of inducible NO-synthase (iNOS) with confocal microscopy. Results: RX treatment, in doses lacking effects on basal insulin, greatly amplified insulin release stimulated by the NO-generating secretagogues glucose and carbachol both in vitro and in vivo. RX also improved the glucose tolerance curve. Islets incubated at high glucose (20 mmol/l) displayed increased NO production derived from both neuronal constitutive NO-synthase (ncNOS) and iNOS. RX abrogated this glucose-induced NO production concomitant with amplification of insulin release. Confocal microscopy revealed abundant iNOS expression in beta-cells after incubation of islets at high but not low glucose. This was abolished after RX treatment. Similarly, islets cultured for 24 h at high glucose showed intense iNOS expression in beta-cells. This was abrogated with RX and followed by an amplified glucose-induced insulin release. Conclusion: RX effectively counteracts the negative impact of beta-cell NO generation on insulin release stimulated by glucose and carbachol suggesting imidazoline compounds by virtue of NOS-inhibitory properties being of potential therapeutic value for treatment of beta-cell dysfunction in hyperglycaemia and type 2 diabetes.
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| 9. |
- Rahman, Awahan, et al.
(författare)
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The role of Caveolin-1 in cardiovascular regulation.
- 2009
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; Sep 25, s. 231-245
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Caveolae are omega-shaped membrane invaginations present in essentially all cell types in the cardiovascular system, and numerous functions have been ascribed to these structures. Caveolae formation depends on caveolins, cholesterol, and PTRF-Cavin (polymerase I and transcript release factor-Cavin). The current review summarizes and critically discusses the cardiovascular phenotypes reported in caveolin-1-deficient mice. Major changes in the structure and function of heart, lung, and blood vessels have been documented, suggesting that caveolae play a critical role at the interface between blood and surrounding tissue. According to an emerging paradigm many of these changes are secondary to uncoupling of endothelial nitric oxide synthase. Thus, nitric oxide synthase not only synthesizes more nitric oxide in the absence of caveolin-1, but also more superoxide with potential pathogenic consequences. It is further argued that the vasodilating drive from increased nitric oxide production in caveolin-1-deficient mice is balanced by changes in the vascular media that favour increased dynamic resistance regulation. Harnessing the therapeutic opportunities buried in caveolae, while challenging, could expand the arsenal of treatment options in cancer, lung disease, and atherosclerosis.
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| 10. |
- Rådegran, Göran
(författare)
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Exercise limb blood flow response to acute and chronic hypoxia in Danish lowlanders and Aymara natives
- 2008
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 192:4, s. 531-539
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The femoral artery blood flow response to submaximal, one-legged, dynamic, knee-extensor exercise was determined in acute and chronic hypoxia to investigate the hypotheses that with adaptation to chronic hypoxia blood haemoglobin increases, allowing preservation of blood flow as in normoxia. Methods: Sixteen Danish lowlanders participated, in groups of six to eight, in the experiments at sea level normoxia (FiO(2) congruent to 0.21) and acute hypoxia (FiO(2) congruent to 0.11), and chronic hypoxia after similar to 7 and 9-10 weeks at similar to 5260 m altitude breathing ambient air (FiO(2) congruent to 0.21) or a hyperoxic gas (FiO(2) congruent to 0.55). The response was compared with that in six Aymara natives. Results: The haemoglobin and haematocrit increased (P < 0.003) in the lowlanders at altitude vs. at sea level by similar to 39 and 27% respectively; i.e. to a similar (P = ns) level as in the natives. At rest, blood flow was the same (P = ns) in the lowlanders at sea level and altitude, as in the natives at altitude. During the onset of and incremental exercise, blood flow was the same (P = ns) in the lowlanders at sea level and altitude, as in the natives at altitude. Acute hypoxia increased (P < 0.05) blood flow by similar to 55% during exercise in the lowlanders at sea level. Acute hyperoxia decreased (P < 0.05) blood flow by similar to 22-29% during exercise in the lowlanders and natives at altitude. Conclusion: In chronic hypoxia, blood haemoglobin increases, allowing normalization of the elevated exercise blood flow response in acute hypoxia, and preservation of the kinetics and steady-state exercise blood flow as in normoxia, being similar as in the natives at altitude.
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| 11. |
- Fredholm, B, et al.
(författare)
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Purines - 80 years and very much alive
- 2010
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Ingår i: Acta physiologica (Oxford, England). - : Wiley. - 1748-1716 .- 1748-1708. ; 199:2, s. 91-92
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 12. |
- Henriksson, J
(författare)
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Human movement science
- 2012
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Ingår i: Acta physiologica (Oxford, England). - : Wiley. - 1748-1716 .- 1748-1708. ; 205:3, s. 321-323
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Alstermark, Bror, et al.
(författare)
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The C3-C4 propriospinal system in the cat and monkey: a spinal pre-motoneuronal centre for voluntary motor control.
- 2007
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Ingår i: Acta physiologica (Oxford, England). - : Wiley. - 1748-1708 .- 1748-1716. ; 189:2, s. 123-40
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Tidskriftsartikel (refereegranskat)abstract
- This review deals with a spinal interneuronal system, denoted the C3-C4 propriospinal system, which is unique in the sense that it so far represents the only spinal interneuronal system for which it has been possible to demonstrate a command mediating role for voluntary movements. The C3-C4 propriospinal neurones govern target reaching and can update the descending cortical command when a fast correction is required of the movement trajectory and also integrate signals generated from the forelimb to control deceleration and termination of reaching.
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| 17. |
- Apró, William, et al.
(författare)
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Influence of supplementation with branched-chain amino acids in combination with resistance exercise on p70S6 kinase phosphorylation in resting and exercising human skeletal muscle.
- 2010
-
Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 200:3, s. 237-48
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Skeletal muscle growth is thought to be regulated by the mammalian target of rapamycin (mTOR) pathway, which can be activated by resistance exercise and branched-chain amino acids (BCAA). The major aim of the present study was to distinguish between the influence of resistance exercise and BCAA on key enzymes considered to be involved in the regulation of protein synthesis, including p70(S6) kinase (p70(S6k)). METHODS: Nine healthy subjects (four men and five women) performed unilateral resistance exercise on two occasions separated by 1 month. Subjects were randomly supplied either a mixture of BCAA or flavoured water. Muscle biopsies were taken from both resting and exercising muscle before, after and 1 h after exercise. RESULTS: Phosphorylation of Akt was unaltered by either resistance exercise and/or BCAA supplementation whereas mTOR phosphorylation was enhanced (P<0.05) to a similar extent in both exercising and resting muscle following exercise in the absence (70-90%) and presence of BCAA supplementation (80-130%). Phosphorylation of p70(S6k) was unaffected by resistance exercise alone; however, BCAA intake increased (P<0.05) this phosphorylation in both legs following exercise. In resting muscle, a 5- and 16-fold increase in p70(S6k) was observed immediately after and 1 h after exercise, respectively, as compared to 11- and 30-fold increases in the exercising muscle. Phosphorylation of eukaryotic elongation factor 2 was attenuated 1 h after exercise (P<0.05) in both resting (10-40%) and exercising muscle (30-50%) under both conditions. CONCLUSION: The present findings indicate that resistance exercise and BCAA exert both separate and combined effects on the p70(S6k) phosphorylation in an Akt-independent manner.
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| 18. |
- A'Roch, Roman, 1959-, et al.
(författare)
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Left ventricular mechanical dyssynchrony is load independent at rest and during endotoxaemia in a porcine model
- 2009
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 196:4, s. 375-383
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Tidskriftsartikel (refereegranskat)abstract
- AIM: In diseased or injured states, the left ventricle displays higher degrees of mechanical dyssynchrony. We aimed at assessing mechanical dyssynchrony ranges in health related to variation in load as well as during acute endotoxin-induced ventricular injury. METHODS: In 16 juvenile anaesthetized pigs, a five-segment conductance catheter was placed in the left ventricle as well as a balloon-tipped catheter in the inferior vena cava. Mechanical dyssynchrony during systole, including dyssynchrony time in per cent during systole and internal flow fraction during systole, were measured at rest and during controlled pre-load reduction sequences, as well as during 3 h of endotoxin infusion (0.25 microg kg(-)1 h(-1)). RESULTS: Systolic dyssynchrony and internal flow fraction did not change during the course of acute beat-to-beat pre-load alteration. Endotoxin-produced acute pulmonary hypertension by left ventricular dyssynchrony measures was not changed during the early peak of pulmonary hypertension. Endotoxin ventricular injury led to progressive increases in systolic mechanical segmental dyssynchrony (7.9 +/- 1.2-13.0 +/- 1.3%) and ventricular systolic internal flow fraction (7.1 +/- 2.4-16.6 +/- 2.8%), respectively for baseline and then at hour 3. There was no localization of dyssynchrony changes to segment or region in the ventricular long axis during endotoxin infusion. CONCLUSION: These results suggest that systolic mechanical dyssynchrony measures may be load independent in health and during acute global ventricular injury by endotoxin. More study is needed to validate ranges in health and disease for parameters of mechanical dyssynchrony.
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| 19. |
- Asgeirsson, D., et al.
(författare)
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Glomerular sieving of three neutral polysaccharides, polyethylene oxide and bikunin in rat. Effects of molecular size and conformation
- 2007
-
Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 191:3, s. 237-246
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: Polysaccharides and many other non-protein polymers generally have a more open, flexible and asymmetrical structure compared with globular proteins. For a given molecular weight (MW), the Stokes–Einstein radius (ae) of the following polymers increases in the order: Ficoll < dextran ≤ pullulan < polyethylene oxide (PEO). We have tested the hypothesis that such an increase in 'molecular extension' will increase the molecule's glomerular permeability. Thus, we investigated the glomerular sieving coefficients (θ) of the mentioned polymers and of the negatively charged and extended protein bikunin. Methods: In anaesthetized Wistar rats, glomerular sieving curves were generated for each FITC-labelled polymer from their respective concentration in urine and plasma, determined by size exclusion chromatography. The θ for bikunin was measured using a tissue uptake technique. Results: For a molecule of ae = 55 Å (cf. IgG), θ increased in the order: Ficoll (0.00035 ± 0.000013) < dextran (0.022 ± 0.0029) < pullulan (0.033 ± 0.0024) < PEO (0.12 ± 0.0055). For ae = 36 Å (cf. albumin) the order was: Ficoll (0.076 ± 0.0061) < dextran (0.45 ± 0.037) = pullulan (0.45 ± 0.021) < PEO (0.65 ± 0.0076). θ for bikunin (0.089 ± 0.0045) was 150 times higher than that of albumin, having an equivalent ae and net negative charge. Conclusion: From these results it is concluded that for flexible and asymmetric macromolecules, their degree of glomerular hyperpermeability is proportional to their degree of 'molecular extension'. Thus, compared with globular proteins, the polysaccharides investigated, including Ficoll, were found to be hyperpermeable across the glomerular filter in vivo.
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| 20. |
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| 21. |
- Bajor, Antal, 1962, et al.
(författare)
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Indirect evidence for increased mechanosensitivity of jejunal secretomotor neurones in patients with idiopathic bile acid malabsorption.
- 2009
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Ingår i: Acta physiologica (Oxford, England). - : Wiley. - 1748-1716 .- 1748-1708. ; 197:2, s. 129-37
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Tidskriftsartikel (refereegranskat)abstract
- The interdigestive motor rhythm, the migrating motor complex (MMC), is accompanied by active secretion of chloride during periods of distally propagating maximal motor activity (MMC phase III). We studied the behaviour of this system in bile acid malabsorption (BAM), a relative common cause of chronic diarrhoea. We measured motor activity and transmucosal potential difference (PD, reflecting active chloride secretion), in the proximal jejunum in healthy controls (n = 18) and in a group of patients with BAM (n = 11). The phase III-generated voltage was related to the degree of BAM quantified by the (75)SeHCAT test.
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| 22. |
- Bak, Zoltan, et al.
(författare)
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Human cardiovascular dose-response to supplemental oxygen
- 2007
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 191:1, s. 15-24
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of the study was to examine the central and peripheral cardiovascular adaptation and its coupling during increasing levels of hyperoxaemia. We hypothesized a dose-related effect of hyperoxaemia on left ventricular performance and the vascular properties of the arterial tree. Methods: Oscillometrically calibrated arterial subclavian pulse trace data were combined with echocardiographic recordings to obtain non-invasive estimates of left ventricular volumes, aortic root pressure and flow data. For complementary vascular parameters and control purposes whole-body impedance cardiography was applied. In nine (seven males) supine, resting healthy volunteers, aged 23–48 years, data was collected after 15 min of air breathing and at increasing transcutaneous oxygen tensions (20, 40 and 60 kPa), accomplished by a two group, random order and blinded hyperoxemic protocol. Results: Left ventricular stroke volume [86 ± 13 to 75 ± 9 mL (mean ± SD)] and end-diastolic area (19.3 ± 4.4 to 16.8 ± 4.3 cm2) declined (P < 0.05), and showed a linear, negative dose–response relationship to increasing arterial oxygen levels in a regression model. Peripheral resistance and characteristic impedance increased in a similar manner. Heart rate, left ventricular fractional area change, end-systolic area, mean arterial pressure, arterial compliance or carbon dioxide levels did not change. Conclusion: There is a linear dose–response relationship between arterial oxygen and cardiovascular parameters when the systemic oxygen tension increases above normal. A direct effect of supplemental oxygen on the vessels may therefore not be excluded. Proximal aortic and peripheral resistance increases from hyperoxaemia, but a decrease of venous return implies extra cardiac blood-pooling and compensatory relaxation of the capacitance vessels.
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| 23. |
- Bakkman, Linda, et al.
(författare)
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Quantitative and qualitative adaptation of human skeletal muscle mitochondria to hypoxic compared to
- 2007
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 190:3, s. 243-251
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To investigate if training during hypoxia (H) improves the adaptation of muscle oxidative function compared with normoxic (N) training performed at the same relative intensity. METHOD: Eight untrained volunteers performed one-legged cycle training during 4 weeks in a low-pressure chamber. One leg was trained under N conditions and the other leg under hypobaric hypoxia (526 mmHg) at the same relative intensity as during N (65% of maximal power output, W(max)). Muscle biopsies were taken from vastus lateralis before and after the training period. Muscle samples were analysed for the activities of oxidative enzymes [citrate synthase (CS) and cytochrome c oxidase (COX)] and mitochondrial respiratory function. RESULTS: W(max) increased with more than 30% over the training period during both N and H. CS activity increased significantly after training during N conditions (+20.8%, P < 0.05) but remained unchanged after H training (+4.5%, ns) with a significant difference between conditions (P < 0.05 H vs. N). COX activity was not significantly changed by training and was not different between exercise conditions [+14.6 (N) vs. -2.3% (H), ns]. Maximal ADP stimulated respiration (state 3) expressed per weight of muscle tended to increase after N (+31.2%, P < 0.08) but not after H training (+3.2%, ns). No changes were found in state four respiration, respiratory control index, P/O ratio, mitochondrial Ca(2+) resistance and apparent Km for oxygen. CONCLUSION: The training-induced increase in muscle oxidative function observed during N was abolished during H. Altitude training may thus be disadvantageous for adaptation of muscle oxidative function.
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| 24. |
- Bakkman, L., et al.
(författare)
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Quantitative and qualitative adaptation of human skeletal muscle mitochondria to hypoxic compared to normoxic training at the same relative work rate
- 2007
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Ingår i: Acta Physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X .- 1748-1708 .- 1748-1716. ; 190:3, s. 243-251
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To investigate if training during hypoxia (H) improves the adaptation of muscle oxidative function compared with normoxic (N) training performed at the same relative intensity.Method: Eight untrained volunteers performed one-legged cycle training during 4 weeks in a low-pressure chamber. One leg was trained under N conditions and the other leg under hypobaric hypoxia (526 mmHg) at the same relative intensity as during N (65% of maximal power output, Wmax). Muscle biopsies were taken from vastus lateralis before and after the training period. Muscle samples were analysed for the activities of oxidative enzymes [citrate synthase (CS) and cytochrome c oxidase (COX)] and mitochondrial respiratory function.Results: W max increased with more than 30% over the training period during both N and H. CS activity increased significantly after training during N conditions (+20.8%, P < 0.05) but remained unchanged after H training (+4.5%, ns) with a significant difference between conditions (P < 0.05 H vs. N). COX activity was not significantly changed by training and was not different between exercise conditions [+14.6 (N) vs. -2.3% (H), ns]. Maximal ADP stimulated respiration (state 3) expressed per weight of muscle tended to increase after N (+31.2%, P < 0.08) but not after H training (+3.2%, ns). No changes were found in state four respiration, respiratory control index, P/O ratio, mitochondrial Ca2+ resistance and apparent Km for oxygen.Conclusion: The training-induced increase in muscle oxidative function observed during N was abolished during H. Altitude training may thus be disadvantageous for adaptation of muscle oxidative function.
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| 25. |
- Bengtsson, Magnus W., et al.
(författare)
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Duodenal bicarbonate secretion in rats : Stimulation by intra-arterial and luminal guanylin and uroguanylin
- 2007
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 191:4, s. 309-317
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Uroguanylin and guanylin are endogenous ligands for guanylate cyclase C, an upstream regulator of the cystic fibrosis transmembrane resistance (CFTR) anion channel, and both peptides increase intestinal anion export in vitro. We have compared the effects of close intra-arterial and luminal administration of uroguanylin and guanylin on duodenal bicarbonate secretion in vivo and studied the interactions with melatonin and cholinergic stimulation. Methods: Lewis × Dark Agouti rats were anaesthetized and a segment of the proximal duodenum with intact blood supply was cannulated in situ. Mucosal bicarbonate secretion (pH stat) was continuously recorded and peptides were infused intra-arterially or added to the luminal perfusate. Results: Intra-arterial (50–1000 pmol kg−1 h−1) as well as luminal administration (50–500 nmol L−1) of guanylin or uroguanylin caused dose-dependent increases in the duodenal secretion. Luminal administration induced more rapidly appearing rises in secretion and the two peptides induced secretory responses of similar shape and magnitude. The melatonin MT2-selective antagonist luzindole (600 nmol kg−1) significantly depressed the response to intra-arterial guanylins but did not affect secretion induced by luminal guanylins. Similarly, the muscarinic antagonist atropine (0.75 μmol kg−1 followed by 0.15 μmol kg−1 h−1) abolished the response to intra-arterial uroguanylin but caused only slight suppression of the response to luminal uroguanylin. Conclusions: Intra-arterial as well as luminal uroguanylin and guanylin are potent stimuli of duodenal mucosal bicarbonate secretion in vivo. The response to luminal guanylins reflects an action at apical receptors. Stimulation by parenteral guanylins, in contrast, is under cholinergic influence and interacts with melatonin produced by mucosal enteroendocrine cells.
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| 26. |
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| 27. |
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| 28. |
- Carlström, Mattias, et al.
(författare)
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Hydronephrosis causes salt-sensitive hypertension and impaired renal concentrating ability in mice
- 2007
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 189:3, s. 293-301
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Hypertension is a common disease in the industrialized world and approximately 5% of all cases are secondary to kidney malfunction. We have recently shown that hydronephrosis due to partial unilateral ureteral obstruction (PUUO) causes salt-sensitive hypertension in rats. The mechanisms are still unclear, but appear to be intrarenal and primarily located to the diseased kidney. In the present study, we have developed a model for PUUO to study if hydronephrotic mice develop salt-sensitive hypertension. Methods: PUUO was created in 3-week-old mice (C57bl/6J). Blood pressure and heart rate were measured telemetrically in adult animals on normal and high salt diets. Metabolism cages were used to study the renal excretion of electrolytes and water. Plasma samples for renin analysis were collected and renal histological changes were evaluated. Results: All hydronephrotic animals developed salt-sensitive hypertension that correlated to the degree of hydronephrosis. In hydronephrotic animals, blood pressure increased from 114 ± 1 mmHg on normal salt diet to 120 ± 2 mmHg on high salt diet, compared with 103 ± 1 to 104 ± 1 in controls. Hydronephrotic animals showed increased diuresis and reduced ability to regulate electrolyte concentration. No differences in plasma renin concentration were found between the groups. The parenchymal weight and glomerular area of contralateral kidneys were significantly increased in the hydronephrotic animals. Histopathology of the hydronephrotic kidneys displayed areas with fibrosis, inflammation and glomerular changes. Conclusion: This study provides a model for PUUO in mice and demonstrates the presence of salt-sensitive hypertension and an impaired renal concentrating ability in mice which has not been described before.
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| 29. |
- Carlström, Mattias, et al.
(författare)
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Relief of chronic partial ureteral obstruction attenuates salt-sensitive hypertension in rats
- 2007
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 189:1, s. 67-75
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The incidence of hydronephrosis due to ureteropelvic junction obstruction is approx. 0.5%. During the last decade, the management of non-symptomatic hydronephrosis has become much more conservative, but the long-term physiological consequences of this policy are not clear. Previously, we have shown that animals with chronic partial unilateral ureteral obstruction develop salt-sensitive hypertension. In this study, the effects of ipsilateral and contralateral nephrectomy and ureterovesicostomy on blood pressure were studied in hydronephrotic animals. Methods: Partial unilateral ureteral obstruction was created in 3-week-old male Sprague–Dawley rats and blood pressure was measured telemetrically 4–6 weeks later during a normal and high salt diet before and after uninephrectomy or ureterovesicostomy. Plasma samples for renin assay were collected during both diets before and after ipsilateral nephrectomy. Results: All hydronephrotic animals developed salt-sensitive hypertension, of different degrees. Before nephrectomy the plasma renin concentration was significantly higher in the hydronephrotic animals than in controls (160 ± 15 μGU mL−1 vs. 96 ± 12 μGU mL−1, respectively), but after the ipsilateral nephrectomy no differences were found between the groups. In the hydronephrotic animals both ipsilateral nephrectomy and ureterovesicostomy reduced the blood pressure and salt-sensitivity but the former still differed significantly from the controls. In contralaterally, nephrectomized hydronephrotic animals the salt-sensitive hypertension became more pronounced. Conclusion: Hydronephrosis in rats causes salt-sensitive hypertension that can be markedly reduced by removing the hydronephrotic kidney or relieving the obstruction by ureterovesicostomy. The mechanisms appear to be intrarenal and primarily located in the diseased kidney, but a secondary mechanism is also present.
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| 30. |
- Cristea, Alexander, et al.
(författare)
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Effects of combined strength and sprint training on regulation of muscle contraction at the whole-muscle and single fibre levels in elite master sprinters
- 2008
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 193:3, s. 275-289
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Tidskriftsartikel (refereegranskat)abstract
- AIM: This study aims at examining the effects of progressive strength and sprint training on regulation of muscle contraction at the whole-muscle and single-fibre levels in older sprint-trained athletes. METHODS: Eleven men (52-78 years) were randomized to a training (EX, n = 7) or control (CTRL, n = 4) group. EX participated in a 20-week programme that combined sprint training with heavy and explosive strength exercises, while CTRL maintained their usual run-based training schedules. RESULTS: EX improved maximal isometric and dynamic leg strength, explosive jump performance and force production in running. Specific tension and maximum shortening velocity of single fibres from the vastus lateralis were not altered in EX or CTRL. Fibre type and myosin heavy chain isoform distributions remained unchanged in the two groups. There was a general increase in fibre areas in EX, but this was significant only in IIa fibres. The 10% increase in squat jump in EX was accompanied by a 9% increase in the integrated EMG (iEMG) of the leg extensors but the 21-40% increases in isometric and dynamic strength were not paralleled by changes in iEMG. CONCLUSION: Adding strength training stimulus to the training programme improved maximal, explosive and sport-specific force production in elite master sprinters. These improvements were primarily related to hypertrophic muscular adaptations.
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| 31. |
- Danielsson, T, et al.
(författare)
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Resistin increases islet blood flow and decreases subcutaneous adipose tissue blood flow in anaesthetized rats
- 2009
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 195:2, s. 283-288
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Resistin is an adipokine which has been suggested to participate in the induction of insulin resistance associated with type 2 diabetes. The aim of the present study was to investigate whether acute administration of resistin influences tissue blood perfusion in rats. METHODS: Resistin was administered as an intravenous infusion of 7.5 microg h(-1) (1.5 mL h(-1)) for 30 min to rats anaesthetized with thiobutabarbital. A microsphere technique was used to estimate the blood flow to six different depots of white adipose tissue (WAT), brown adipose tissue (BAT), as well as to the pancreas, islets, duodenum, colon, kidneys, adrenal glands and liver. RESULTS: Resistin administration led to an increased blood flow to the pancreas and islets and a decrease in subcutaneous WAT and BAT. Intra-abdominal white adipose tissue blood flow and that to other organs were not affected. CONCLUSION: Acute administration of resistin markedly affects the blood perfusion of both the pancreas and subcutaneous white adipose tissue depots. At present it is unknown whether resistin exerts a direct effect on the vasculature, or works through local or systemic activation of endothelial cells and/or macrophages. The extent to which this might contribute to the insulin resistance caused by resistin is yet unknown.
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| 32. |
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| 33. |
- Ekholm, Marie, et al.
(författare)
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Rapid and easy semi-quantitative evaluation method for diacylglycerol and inositol-1,4,5-trisphosphate generation in orexin receptor signalling
- 2010
-
Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 198:3, s. 387-392
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Fluorescent protein-based indicators have enabled measurement of intracellular signals previously nearly inaccessible for studies. However, indicators showing intracellular translocation upon response suffer from serious limitations, especially the very time-consuming data collection. We therefore set out in this study to evaluate whether fixing and counting cells showing translocation could mend this issue. Methods: Altogether three different genetically encoded indicators for diacylglycerol and inositol-1,4,5-trisphosphate were transiently expressed in Chinese hamster ovary cells stably expressing human OX1 orexin receptors. Upon stimulation with orexin-A, the cells were fixed with six different protocols. Results: Different protocols showed clear differences in their ability to preserve the indicator’s localization (i.e. translocation after stimulus) and its fluorescence, and the best results for each indicator were obtained with a different protocol. The concentration Conclusion: The counting method, as used here, works at single time point and looses the single-cell-quantitative aspect. However, it also has some useful properties. First, it easily allows processing of a 100- to 1000-fold higher cell numbers than real-time imaging producing statistically consistent population-quantitative data much faster. Secondly, it does not require expensive real-time imaging equipment. Fluorescence in fixed cells can also be quantitated, though this analysis would be more time-consuming than cell counting. Thirdly, in addition to the quantitative data collection, the method could be applied for identifying responsive cells. This might be very useful in identification of e.g. orexin-responding neurones in a large population of non-responsive cells in primary cultures.
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| 34. |
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| 35. |
- Esbjörnsson, M, et al.
(författare)
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Sprint exercise enhances skeletal muscle p70S6k phosphorylation and more so in women than in men.
- 2012
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 205:3, s. 411-22
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Sprint exercise is characterized by repeated sessions of brief intermittent exercise at a high relative workload. However, little is known about the effect on mTOR pathway, an important link in the regulation of muscle protein synthesis. An earlier training study showed a greater increase in muscle fibre cross-sectional area in women than men. Therefore, we tested the hypothesis that the activation of mTOR signalling is more pronounced in women than in men. Healthy men (n=9) and women (n=8) performed three bouts of 30-s sprint exercise with 20-min rest in between.METHODS: Multiple blood samples were collected over time, and muscle biopsy specimens were obtained at rest and 140 min after the last sprint.RESULTS: Serum insulin increased by sprint exercise and more so in women than in men [gender (g) × time (t)]: P=0.04. In skeletal muscle, phosphorylation of Akt increased by 50% (t, P=0.001) and mTOR by 120% (t, P=0.002) independent of gender. The elevation in p70S6k phosphorylation was larger in women (g × t, P=0.03) and averaged 230% (P=0.006) as compared to 60% in men (P=0.04). Phosphorylation rpS6 increased by 660% over time independent of gender (t, P=0.003). Increase in the phosphorylation of p70S6k was directly related to increase in serum insulin (r=0.68, P=0.004).CONCLUSION: It is concluded that repeated 30-s all-out bouts of sprint exercise separated by 20 min of rest increases Akt/mTOR signalling in skeletal muscle. Secondly, signalling downstream of mTOR was stronger in women than in men after sprint exercise indicated by the increased phosphorylation of p70S6k.
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| 36. |
- Ewert, Sara, 1974, et al.
(författare)
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Angiotensin II induced contraction of rat and human small intestinal wall musculature in vitro
- 2006
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 188:1, s. 33-40
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Angiotensin II (Ang II) is a well-known activator of smooth muscle in the vasculature but has been little explored with regard to intestinal wall muscular activity. This study investigates pharmacological properties of Ang II and expression of its receptors in small-intestinal smooth muscle from rats and humans. METHODS: Isometric recordings were performed in vitro on small intestinal longitudinal muscle strips. Protein expressions of Ang II typ 1 (AT1R) and typ 2 (AT2R) receptors were assessed by Western blot. RESULTS: Ang II elicited concentration-dependent contractions of rat jejunal and ileal muscle preparations. The concentration-response curve (rat ileum, EC(50): 1.5 +/- 0.9 x 10(-8) M) was shifted to the right by the AT1R receptor antagonist losartan (10(-7) M) but was unaffected by the AT2R antagonist PD123319 (10(-7) M) as well as by the adrenolytic guanethidine (3 x 10(-6) M) and the anticholinergic atropine (10(-6) M). Human duodenal, jejunal and ileal longitudinal muscle preparations all contracted concentration-dependently in response to Ang II. The concentration-response curve (human jejunum, EC(50): 1.5 +/- 0.8 x 10(-8) M) was shifted to the right by losartan (10(-7) M) but was unaffected by PD123319 (10(-7) M). Both AT1R and AT2R were detected in all segments of the rat small intestinal wall musculature, whereas only AT1R was readily detectable in the human samples. CONCLUSION: Ang II elicits contractions of small-intestinal longitudinal muscle preparations from the small intestine of rats and man. The pharmacological pattern and protein expression analyses indicate mediation via the AT1R.
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| 37. |
- Flemström, Gunnar, 1941-, et al.
(författare)
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Apelin stimulation of duodenal bicarbonate secretion : feeding-dependent and mediated via apelin-induced release of enteric cholecystokinin
- 2011
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Ingår i: Acta Physiologica. - Oxford : Wiley-Blackwell. - 1748-1708 .- 1748-1716. ; 201:1, s. 141-150
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Apelin peptides is the endogenous ligand of the G protein-coupled receptor APJ. Proposed actions include involvement in control of cardiovascular functions, appetite and body metabolism. We have investigated effects of apelin peptides on duodenal bicarbonate secretion in vivo and the release of cholecystokinin (CCK) from acutely isolated mucosal cells and the neuroendocrine cell line STC-1. Methods: Lewis x Dark Agouti rats had free access to water and, unless fasted overnight, free access to food. A segment of proximal duodenum was cannulated in situ in anesthetized animals. Mucosal bicarbonate secretion was titrated (pH stat) and apelin was administered to the duodenum by close intra-arterial infusion. Total RNA was extracted from mucosal specimens, reverse transcripted to cDNA and expression of the APJ receptor measured by quantitative real-time PCR. Apelin-induced release of CCK was measured using (i) cells prepared from proximal small intestine, and (ii) STC-1 cells. Results: Even the lowest dose of apelin-13 (6 pmol kg-1 h-1) caused a significant rise in bicarbonate secretion. Stimulation occurred only in continuously fed animals and even a 100-fold greater dose (600 pmol kg-1 h-1) of apelin was without effect in overnight food deprived animals. Fasting also induced a 8-fold decrease in the expression of APJ receptor mRNA. Apelin induced significant release of CCK from both mucosal and STC-1 cells, and the CCKA receptor antagonist devazepide abolished bicarbonate secretory responses to apelin. Conclusions: Apelin-induced stimulation of duodenal electrolyte secretion is feeding dependent and mediated by local mucosal release of CCK
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| 38. |
- Flemström, Gunnar, 1941-, et al.
(författare)
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Effects of short-term food deprivation on orexin-A-induced intestinal bicarbonate secretion in comparison with related secretagogues
- 2010
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Ingår i: Acta Physiologica. - Oxford : Wiley-Blackwell. - 1748-1708 .- 1748-1716. ; 198:3, s. 373-380
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Forskningsöversikt (refereegranskat)abstract
- Studies of gastrointestinal physiology in humans and intact animals are usually conducted after overnight fast. We have compared effects of orexin-A, vasoactive intestinal polypeptide (VIP), melatonin, serotonin, uroguanylin, ghrelin and prostaglandin E2 (PGE2) on duodenal bicarbonate secretion in fed and overnight fasted animals. This review is a summary of our findings. Secretagogues were administered by intra-arterial infusion or luminally (PGE2) Enterocyte intracellular calcium ([Ca2+]i) signaling was studied by fluorescence imaging. Total RNA was extracted, reverse transcripted to cDNA and expression of orexin receptors measured by quantitative real-time PCR. Orexin-A stimulates the duodenal secretion in continuously fed animals but not in food deprived animals. Similarly, short fasting causes a 100-fold decrease of the amount of the muscarinic agonist bethanechol required for stimulation of secretion. In contrast, fasting does not affect secretory responses to intra-arterial VIP, melatonin, serotonin, uroguanylin and ghrelin, or that to luminal PGE2. Orexin-A induces [Ca2+]i signaling in enterocytes from fed rats but no significant [Ca2+]i responses occurs in enterocytes from fasted animals. In addition, overnight fasting decreases the expression of mucosal and enterocyte orexin receptors. Short food deprivation thus decreases duodenal expression of orexin receptors and abolishes the secretory response to orexin-A as well as orexin-A induced [Ca2+]i signaling. Fasting, furthermore, decreases mucosal sensitivity to bethanechol. The absence of declines in secretory responses to other secretagogues tested is strong evidence that short fasting does affect not the secretory capacity of the duodenal mucosa in general. Studies of intestinal secretion require particular evaluation with respect to feeding status.
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| 39. |
- Folkesson, Mattias, 1972-, et al.
(författare)
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Immunohistochemical changes in the expression of HSP27 in exercised human vastus lateralis muscle
- 2008
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Ingår i: Acta Physiologica. - : Blackwell Publishing. - 1748-1708 .- 1748-1716. ; 194:3, s. 215-222
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The role of HSP27 in the adaptive process of skeletal muscle to exercise, especially in humans, is not well understood. The objective of this study was to investigate immunohistochemical changes in HSP27 expression in human vastus lateralis muscle following resistance and endurance exercises.Methods: Two different exercise protocols were used: (1) one-leg ergometer cycling (EC, n = 6) consisting of two 30-min bouts at 40% and 75% of peak oxygen uptake, respectively, and (2) leg extension resistance exercise (RE, n = 9) including 10 sets of eight repetitions at a load corresponding to 70% of one maximal repetition (1RM). Immunohistochemistry using specific monoclonal antibodies was used to determine the location of HSP27 protein in muscle biopsies from human vastus lateralis.Results: Our results show that RE, but not EC, induced a significant appearance of scattered accumulations of HSP27 protein in muscle fibres from five of nine subjects. The number of fibres with accumulation of HSP27 in RE ranged from 0% to 32% with a mean of 6.3% of the total number of fibres.Conclusion: We conclude that this rapid HSP27 protein relocation after RE is an important player in the cellular remodelling of human muscle fibres in response to exercise involving high-force contractions, but not in response to endurance exercises.
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| 40. |
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| 41. |
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| 42. |
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| 43. |
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| 44. |
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| 45. |
- Hansson, Elisabeth, 1955
(författare)
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Could chronic pain and spread of pain sensation be induced and maintained by glial activation?
- 2006
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Ingår i: Acta physiologica (Oxford, England). - : Wiley. - 1748-1708 .- 1748-1716. ; 187:1-2, s. 321-7
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Tidskriftsartikel (refereegranskat)abstract
- An injury often starts with acute physiological pain, which becomes inflammatory or neuropathic, and may sometimes become chronic. It has been proposed recently that activated glial cells, astrocytes and microglia within the central nervous system could maintain the pain sensation even after the original injury or inflammation has healed, and convert it into chronic by altering neuronal excitability. Glial cell activation has also been proposed to be involved in the phenomenon of spread of pain sensation ipsilaterally or to the contralateral side (i.e. mirror image pain). Substance P and calcitonin gene-related peptide, released due to an inflammatory process, interact with the endothelial cells of the blood-spinal cord and blood-brain barriers. The barriers open partially and substances may influence adjacent glial cells. Such substances are also released from neurones carrying the 'pain message' all the way from the injury to the cerebral cortex. Pro-inflammatory cytokines may be released from the microglial cells, and astroglial Ca2+-transients or oscillations may spread within the astroglial networks. One theory is that Ca2+-oscillations could facilitate the formation of new synapses. These new synapses could establish neuronal contacts for maintaining and spreading the pain sensation. If this theory holds true, it is possible that Ca2+ waves, production of cytokines and growth factors could be modified by selective anti-inflammatory drugs to achieve a balance in the activities of the different intercellular and intracellular processes. This paper reviews current knowledge about glial mechanisms underlying the phenomena of chronic pain and spread of the pain sensation.
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| 46. |
- Hellström, Per M., 1954-
(författare)
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GLP-1 playing the role of a gut regulatory compound
- 2011
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 201:1, s. 151-156
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Forskningsöversikt (refereegranskat)abstract
- Gastric emptying is the first step in the metabolic endocrine cascade that takes place after food intake. The incretin hormones originating in the gut, particularly GLP-1, exert multiple antihyperglycaemic actions such as enhancement of glucose-dependent insulin secretion, suppression of glucagon secretion, slowing of gastric emptying with an ensuing decrease in food intake and weight loss. From extensive studies in experimental animals and humans we have found that GLP-1 also exerts a motility-inhibiting and antispasmodic effect in the gut that was verified in healthy volunteers and patients with irritable bowel syndrome (IBS). In order to further investigate the effect of GLP-1 in humans, we used the dipeptidyl peptidase-IV resistant GLP-1 analogue ROSE-010, thereby extending its biological activity. A randomized, double-blinded, prospective clinical trial was carried out in order to investigate the effect of two doses of ROSE-010 in 166 patients suffering from pain attacks of IBS. We found that injections of ROSE-010 were twice as effective as placebo in terms of total pain relief response in those affected by pain attacks due to IBS. Our results show that basal physiological research studies can be translated into clinical use. The current pharmaceutical incentive with incretin mimetics, such as GLP-1 analogues and exenatide, is an interesting development that apart from its obvious use in diabetes type 2, may also be useful in terms of gut motility-regulating effects with effects on appetite, food intake and motility disorders that may provide an opportunity to bring about new improvements in medical care.
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| 47. |
- Holtermann, A., et al.
(författare)
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Differential activation of regions within the biceps brachii muscle during fatigue
- 2008
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Ingår i: Acta Physiologica. - : Wiley-Blackwell. - 1748-1708 .- 1748-1716. ; 192:4, s. 559-567
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To examine the occurrence of repeated differential activation between the heads of the biceps brachii muscle and its relation to fatigue prevention during a submaximal contraction.Methods: Thirty‐nine subjects carried out an isometric contraction of elbow flexion at 25% of maximal voluntary contraction (MVC) until exhaustion. A grid of 13 by 10 electrodes was used to record surface electromyographic signals from both heads of the biceps brachii. The root‐mean‐square of signals recorded from electrodes located medially and laterally was used to analyse activation differences. Differential activation was defined as periods of 33% different activation level between the two heads of the biceps brachii muscle.Results: Differential muscle activation was demonstrated in 30 of 33 subjects with appropriate data quality. The frequency of differential activation increased from 4.9 to 6.6 min−1 at the end of the contractions with no change in duration of the differential activations (about 1.4 s). Moreover, the frequency of differential activation was, in general, negatively correlated with time to exhaustion.Conclusion: The observed differential activation between the heads of the biceps brachii can be explained by an uneven distribution of synaptic input to the motor neurone pool. The findings of this study indicate that differential activation of regions within a muscle does not prevent fatigue at a contraction level of 25% of MVC.
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| 48. |
- Jansson, Leif, et al.
(författare)
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Pancreatic islet blood flow during euglycaemic, hyperinsulinaemic clamp in anaesthetized rats
- 2007
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 189:4, s. 319-324
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Previous studies have demonstrated that pancreatic islet blood flow is crucially dependent on blood glucose concentration. Thus, hyperglycaemia increases and hypoglycaemia decreases islet blood perfusion, by a combination of nervous and metabolic signals. The aim of the present study was to evaluate if hyperinsulinaemia, without associated hypoglycaemia, affects islet blood flow. Methods: Thiobutabarbital-anaesthetized Wistar–Furth rats were subjected to an euglycaemic, hyperinsulinaemic clamp, that is they were infused for 60 min with either saline, insulin (18 mU kg−1 min−1), glucose (27 mg kg−1 min−1) or both glucose and insulin. This was followed by islet blood flow measurements with a microsphere technique. Results: Animals receiving only glucose doubled their blood glucose and serum insulin concentrations, whereas rats receiving only insulin had blood glucose concentrations <2 mmol L−1 and a 10-fold increase in serum insulin concentrations. Animals given simultaneous glucose and insulin had normal blood glucose concentrations but a 10-fold increase in serum insulin concentrations. Total pancreatic blood flow was unaffected in all animals. Islet blood flow was increased in hyperglycaemic and decreased in hypoglycaemic rats compared with control rats. Islet blood flow did not differ between clamped and control rats. Conclusions: Serum insulin concentration per se does not affect islet blood flow, whereas the ambient blood glucose concentration is of major importance in this context.
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| 49. |
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| 50. |
- Keramidas, Michail E., et al.
(författare)
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Acute normobaric hyperoxia transiently attenuates plasma erythropoietin concentration in healthy males : evidence against the 'normobaric oxygen paradox' theory
- 2011
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Ingår i: Acta Physiologica. - : Wiley-Blackwell. - 1748-1708 .- 1748-1716. ; 202:1, s. 91-98
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The purpose of the present study was to evaluate the 'normobaric oxygen paradox' theory by investigating the effect of a 2-h normobaric O(2) exposure on the concentration of plasma erythropoietin (EPO). Methods: Ten healthy males were studied twice in a single-blinded counterbalanced crossover study protocol. On one occasion they breathed air (NOR) and on the other 100% normobaric O(2) (HYPER). Blood samples were collected Pre, Mid and Post exposure; and thereafter, 3, 5, 8, 24, 32, 48, 72 and 96 h, and 1 and 2 weeks after the exposure to determine EPO concentration. Results: The concentration of plasma erythropoietin increased markedly 8 and 32 h after the NOR exposure (approx. 58% and approx. 52%, respectively, P < 0.05) as a consequence of its natural diurnal variation. Conversely, the O(2) breathing was followed by approx. 36% decrement of EPO 3 h after the exposure (P < 0.05). Moreover, EPO concentration was significantly lower in HYPER than in the NOR condition 3, 5 and 8 h after the breathing intervention (P < 0.05). Conclusion: In contrast to the 'normobaric oxygen paradox' theory, the present results indicate that a short period of normobaric O(2) breathing does not increase the EPO concentration in aerobically fit healthy males. Increased O(2) tension suppresses the EPO concentration 3 and 5 h after the exposure; thereafter EPO seems to change in a manner consistent with natural diurnal variation.
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