| 1. |
- 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
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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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| 2. |
- Addinsall, Alex B., et al.
(författare)
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Ruxolitinib : A new hope for ventilator-induced diaphragm dysfunction
- 2024
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Ingår i: Acta Physiologica. - : John Wiley & Sons. - 1748-1708 .- 1748-1716. ; 240:5
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Mechanical ventilation (MV) results in diminished diaphragm size and strength, termed ventilator-induced diaphragm dysfunction (VIDD). VID increases dependence, prolongs weaning, and increases discharge mortality rates. The Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway is implicated in VIDD, upregulated following MV. JAK/STAT inhibition alleviates chronic muscle wasting conditions. This study aimed to explore the therapeutic potential of Ruxolitinib, an FDA approved JAK1/2 inhibitor (JI) for the treatment of VIDD. Methods: Rats were subjected to 5 days controlled MV (CMV) with and without daily Ruxolitinib gavage. Muscle fiber size and function were assessed. RNAseq, mitochondrial morphology, respirometry, and mass spectrometry were determined. Results: CMV significantly reduced diaphragm size and specific force by 45% (p < 0.01), associated with a two-fold P-STAT3 upregulation (p < 0.001). CMV disrupted mitochondrial content and reduced the oxygen consumption rate (p < 0.01). Expression of the motor protein myosin was unaffected, however CMV alters myosin function via post-translational modifications (PTMs). Daily administration of JI increased animal survival (40% vs. 87%; p < 0.05), restricted P-STAT3 (p < 0.001), and preserved diaphragm size and specific force. JI was associated with preserved mitochondrial content and respiratory function (p < 0.01), and the reversal or augmentation of myosin deamidation PTMs of the rod and head region. Conclusion: JI preserved diaphragm function, leading to increased survival in an experimental model of VIDD. Functional enhancement was associated with maintenance of mitochondrial content and respiration and the reversal of ventilator-induced PTMs of myosin. These results demonstrate the potential of repurposing Ruxolitinib for treatment of VIDD.
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| 4. |
- Ahl, David, et al.
(författare)
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Lactobacillus reuteri increases mucus thickness and ameliorates dextran sulphate sodium-induced colitis in mice
- 2016
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 217:4, s. 300-310
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of this study was to investigate whether two Lactobacillus reuteri strains (rat-derived R2LC and human-derived ATCC PTA 4659 (4659)) could protect mice against colitis, as well as delineate the mechanisms behind this protection.Methods: Mice were given L.reuteri R2LC or 4659 by gavage once daily for 14days, and colitis was induced by addition of 3% DSS (dextran sulphate sodium) to drinking water for the last 7days of this period. The severity of disease was assessed through clinical observations, histological evaluation and ELISA measurements of myeloperoxidase (MPO) and pro-inflammatory cytokines from colonic samples. Mucus thickness was measured invivo with micropipettes, and tight junction protein expression was assessed using immunohistochemistry.Results: Colitis severity was significantly reduced by L.reuteri R2LC or 4659 when evaluated both clinically and histologically. The inflammation markers MPO, IL-1, IL-6 and mKC (mouse keratinocyte chemoattractant) were increased by DSS and significantly reduced by the L.reuteri strains. The firmly adherent mucus thickness was reduced by DSS, but significantly increased by L.reuteri in both control and DSS-treated mice. Expression of the tight junction proteins occludin and ZO-1 was significantly increased in the bottom of the colonic crypts by L.reuteri R2LC.Conclusion: These results demonstrate that each of the two different L. reuteri strains, one human-derived and one-rat-derived, protects against colitis in mice. Mechanisms behind this protection could at least partly be explained by the increased mucus thickness as well as a tightened epithelium in the stem cell area of the crypts.
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| 5. |
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| 6. |
- 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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| 7. |
- Anderberg, Sara B., et al.
(författare)
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Physiological aspects of Toll-like receptor 4 activation in sepsis-induced acute kidney injury
- 2017
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Ingår i: Acta Physiologica. - : Wiley-Blackwell. - 1748-1708 .- 1748-1716. ; 219:3, s. 575-590
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Forskningsöversikt (refereegranskat)abstract
- Sepsis-induced acute kidney injury (SI-AKI) is common and associated with high mortality. Survivors are at increased risk of chronic kidney disease. The precise mechanism underlying SI-AKI is unknown, and no curative treatment exists. Toll-like receptor 4 (TLR4) activates the innate immune system in response to exogenous microbial products. The result is an inflammatory reaction aimed at clearing a potential infection. However, the consequence may also be organ dysfunction as the immune response can cause collateral damage to host tissue. The purpose of this review is to describe the basis for how ligand binding to TLR4 has the potential to cause renal dysfunction and the mechanisms by which this may take place in gram-negative sepsis. In addition, we highlight areas for future research that can further our knowledge of the pathogenesis of SI-AKI in relation to TLR4 activation. TLR4 is expressed in the kidney. Activation of TLR4 causes cytokine and chemokine release as well as renal leucocyte infiltration. It also results in endothelial and tubular dysfunction in addition to altered renal metabolism and circulation. From a physiological standpoint, inhibiting TLR4 in large animal experimental SI-AKI significantly improves renal function. Thus, current evidence indicates that TLR4 has the ability to mediate SI-AKI by a number of mechanisms. The strong experimental evidence supporting a role of TLR4 in the pathogenesis of SI-AKI in combination with the availability of pharmacological tools to target TLR4 warrants future human studies.
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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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
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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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