| 1. |
- Guss, Bengt
(författare)
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Integrin alpha(V)beta(3) can substitute for collagen-binding beta(1)-integrins in vivo to maintain a homeostatic interstitial fluid pressurel
- 2018
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Ingår i: Experimental Physiology. - 0958-0670 .- 1469-445X. ; 103, s. 629-634
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Tidskriftsartikel (refereegranskat)abstract
- Accumulated data indicate that cell-mediated contraction of reconstituted collagenous gels in vitro can serve as a model for cell-mediated control of interstitial fluid pressure (P-IF) in vivo. A central role for collagen-binding beta(1)-integrins in both processes has been established. Furthermore, integrin alpha(V beta 3) takes over the role of collagen-binding beta(1)-integrins in mediating contraction after perturbations of collagen-binding beta(1)-integrins in vitro. Integrin alpha(V beta 3) is also instrumental for normalization of dermal P-IF that has been lowered due to mast cell degranulation with compound 48/80 (C48/80) in vivo. Here we demonstrate a role of integrin alpha(V)beta(3) in maintaining a long term homeostatic dermal P-IF in mice lacking the collagen-binding integrin alpha(111) (alpha 11(-/-) mice). Measurements of P-IF were performed after circulatory arrest. Furthermore, cell-mediated integrin alpha(V)beta(3)-directed contraction of collagenous gels in vitro depends on free access to a collagen site known to bind several extracellular matrix (ECM) proteins that form substrates for (V3)-directed cell attachment, such as fibronectin and fibrin. A streptococcal collagen-binding protein, CNE, specifically binds to and blocks this site on the collagen triple helix. Here we show that whereas CNE perturbed alpha(V beta 3)-directed and platelet-derived growth factor BB-induced normalization of dermal P-IF after C48/80, it did not affect alpha(V beta 3)-dependent maintenance of a homeostatic dermal P-IF. These data imply that dynamic modification of the ECM structure is needed during acute patho-physiological modulations of P-IF but not for long-term maintenance of a homeostatic P-IF. Our data thus show that collagen-binding beta(1)-integrins, integrin alpha(V)beta(3) and ECM structure are potential targets for novel therapy aimed at modulating oedema formation and hypovolemic shock during anaphylaxis.
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| 2. |
- Keramidas, Michail E., et al.
(författare)
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LunHab : interactive effects of a 10 day sustained exposure to hypoxia and bedrest on aerobic exercise capacity in male lowlanders
- 2017
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Ingår i: Experimental Physiology. - : John Wiley & Sons. - 0958-0670 .- 1469-445X. ; 102:6, s. 694-710
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Tidskriftsartikel (refereegranskat)abstract
- NEW FINDINGS: What is the central question of this study? What are the distinct and interactive effects of a 10 day exposure to hypoxia and horizontal bedrest on the whole-body peak oxygen uptake and on the regional cerebral and skeletal muscle tissue oxygenation during upright cycle ergometry in male lowlanders? What is the main finding and its importance? A 10 day sustained exposure to hypoxia aggravates the bedrest-induced reduction in peak oxygen uptake during dynamic exercise engaging large muscle groups, but mitigates the skeletal muscle oxidative capacity impairment elicited by bedrest. The study examined the interactive effects of a 10 day exposure to hypoxia and bedrest on the whole-body peak oxygen uptake (V̇O2 peak ) during maximal exercise and on skeletal muscle and cerebral oxygenation during submaximal exercise. Nine males underwent three 10 day confinements, in a Latin-square order, as follows: (i) a normoxic bedrest [NBR; partial pressure of inspired O2 (PI,O2) = 134.2 ± 0.7 mmHg]; (ii) a hypoxic bedrest (HBR; PI,O2 = 102.9 ± 0.1 mmHg at day 1, 91.5 ± 1.2 mmHg at days 3-10); and (iii) a hypoxic ambulation (HAMB; PI,O2 as in HBR). Before, 1 (R+1) and 3 days (R+3) after each confinement, subjects performed exhaustive, incremental-load and moderate-intensity constant-load (CLTs) cycle-ergometry trials, while breathing either room air or a hypoxic gas mixture. During the CLTs, changes in the regional oxygenation of the cerebral frontal cortex and the vastus lateralis and intercostal muscles were monitored with near-infrared spectroscopy. At R+1, the confinement-related impairment in V̇O2 peak was greater after HBR than after NBR or HAMB, regardless of whether the trial was performed in room air or hypoxia (HBR, -16.2%; NBR, -8.3%; HAMB, -4.1%; P = 0.001). During the CLTs, bedrest aggravated the exercise-induced reduction in locomotor and respiratory muscle oxygenation (P ≤ 0.05); an effect that was less after HBR than after NBR (P ≤ 0.05). The hypoxic exercise-induced cerebral vasodilatory response was blunted by HBR, probably because of the marked hyperventilation-dependent hypocapnia, attendant to the sustained hypoxic stimulus. Hence, short-term exposure to hypoxia potentiates the reduction in V̇O2 peak , but it mitigates the impairment in skeletal muscle oxidative capacity induced by bedrest.
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| 3. |
- Liden, Åsa, et al.
(författare)
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Integrin αVβ3 can substitute for collagen‐binding β1‐integrins in vivo to maintain a homeostatic interstitial fluid pressure
- 2018
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Ingår i: Experimental Physiology. - 0958-0670 .- 1469-445X. ; 103:5, s. 629-634
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Tidskriftsartikel (refereegranskat)abstract
- Accumulated data indicate that cell‐mediated contraction of reconstituted collagenous gels in vitro can serve as a model for cell‐mediated control of interstitial fluid pressure (PIF) in vivo. A central role for collagen‐binding β1‐integrins in both processes has been established. Furthermore, integrin αVβ3 takes over the role of collagen‐binding β1‐integrins in mediating contraction after perturbations of collagen‐binding β1‐integrins in vitro. Integrin αVβ3 is also instrumental for normalization of dermal PIF that has been lowered due to mast cell degranulation with compound 48/80 (C48/80) in vivo. Here we demonstrate a role of integrin αVβ3 in maintaining a long term homeostatic dermal PIF in mice lacking the collagen‐binding integrin α11β1 (α11−/− mice). Measurements of PIF were performed after circulatory arrest. Furthermore, cell‐mediated integrin αVβ3‐directed contraction of collagenous gels in vitro depends on free access to a collagen site known to bind several extracellular matrix (ECM) proteins that form substrates for αVβ3‐directed cell attachment, such as fibronectin and fibrin. A streptococcal collagen‐binding protein, CNE, specifically binds to and blocks this site on the collagen triple helix. Here we show that whereas CNE perturbed αVβ3‐directed and platelet‐derived growth factor BB‐induced normalization of dermal PIF after C48/80, it did not affect αVβ3‐dependent maintenance of a homeostatic dermal PIF. These data imply that dynamic modification of the ECM structure is needed during acute patho‐physiological modulations of PIF but not for long‐term maintenance of a homeostatic PIF. Our data thus show that collagen‐binding β1‐integrins, integrin αVβ3 and ECM structure are potential targets for novel therapy aimed at modulating oedema formation and hypovolemic shock during anaphylaxis.
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| 4. |
- Lindenberger, Marcus, et al.
(författare)
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Slower lower limb blood pooling in young women with orthostatic intolerance.
- 2015
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Ingår i: Experimental Physiology. - : Wiley. - 0958-0670 .- 1469-445X. ; 100:1, s. 2-11
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Tidskriftsartikel (refereegranskat)abstract
- NEW FINDINGS: What is the central question of this study? Orthostatic stress is mostly caused by venous blood pooling in the lower limbs. Venous distension elicits sympathetic responses, and increased distension speed enhances the cardiovascular response. We examine whether lower limb blood pooling rate during lower body negative pressure is linked to orthostatic intolerance. What is the main finding and its importance? A similar amount of blood was pooled in the lower limb, but at a slower rate in women who developed signs of orthostatic intolerance. The difference in blood pooling rate increased with orthostatic stress and was most prominent at a presyncope-inducing level of lower body negative pressure. The findings have implications for the pathophysiology as well as treatment of orthostatic intolerance. Vasovagal syncope is common in young women, but its aetiology remains elusive. Orthostatic stress-induced lower limb blood pooling is linked with central hypovolaemia and baroreceptor unloading. Venous distension in the arm elicits a sympathetic response, which is enhanced with more rapid distension. Our aim was to study both the amount and the speed of lower limb pooling during orthostatic stress and its effects on compensatory mechanisms to maintain cardiovascular homeostasis in women with orthostatic intolerance. Twenty-seven healthy women, aged 20-27 years, were subjected to a lower body negative pressure (LBNP) of 11-44 mmHg. Five women developed symptoms of vasovagal syncope (orthostatic intolerant) and were compared with the remaining women, who tolerated LBNP well (orthostatic tolerant). Lower limb blood pooling, blood flow and compensatory mobilization of venous capacitance blood were measured. Lower body negative pressure induced equal lower limb blood pooling in both groups, but at a slower rate in orthostatic intolerant women (e.g. time to 50% of total blood pooling, orthostatic intolerant 44 ± 7 s and orthostatic tolerant 26 ± 2 s; P < 0.001). At presyncope-inducing LBNP, the mobilization of venous capacitance blood was both reduced (P < 0.05) and much slower in orthostatic intolerant women (P = 0.0007). Orthostatic intolerant women elicited blunted arterial vasoconstriction at low-grade LBNP, activating only cardiopulmonary baroreceptors, while orthostatic tolerant women responded with apparent vasoconstriction (P < 0.0001). In conclusion, slower lower limb blood pooling could contribute to orthostatic intolerance in women. Mobilization of venous capacitance blood from the peripheral to the central circulation was both slower and decreased; furthermore, reduced cardiopulmonary baroreceptor sensitivity was found in women who developed orthostatic intolerance. Further studies including women who experience syncope in daily life are needed.
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| 5. |
- Lucas, Rebekah A. I., et al.
(författare)
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Age-related changes to cardiac systolic and diastolic function during whole-body passive hyperthermia
- 2015
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Ingår i: Experimental Physiology. - : Wiley. - 0958-0670 .- 1469-445X. ; 100:4, s. 422-434
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Tidskriftsartikel (refereegranskat)abstract
- New Findings What is the central question of this study? The effect of ageing on hyperthermia-induced changes in cardiac function is unknown. What is the main finding and its importance? Using echocardiography, we show that during hyperthermia the systolic and diastolic function can be appropriately augmented to meet cardiac demand in healthy older adults, although overall age-related impairments remain. One exception was late diastolic ventricular filling [i.e. E/A ratio and A/(A+E) ratio], which in the older adults was not further augmented during hyperthermia, unlike their young counterparts. To meet cardiac demand, therefore, healthy older adults appear to depend on an increased left ventricular systolic strain and proportion of their cardiac reserve. The effect of ageing on hyperthermia-induced changes in cardiac function is unknown. This study tested the hypothesis that hyperthermia-induced changes in left ventricular systolic and diastolic function are attenuated in older adults when compared with young adults. Eight older (71 +/- 5years old) and eight young adults (29 +/- 5years old), matched for sex, physical activity and body mass index, underwent whole-body passive hyperthermia. Mean arterial pressure (Finometer Pro), heart rate, forearm vascular conductance (venous occlusion plethysmography) and echocardiographic indices of diastolic and systolic function were measured during a normothermic supine period and again after an increase in internal temperature of approximate to 1.0 degrees C. Hyperthermia decreased mean arterial pressure and left ventricular end-diastolic volumes and increased heart rate to a similar extent in both groups (P>0.05). Ageing did not alter the magnitude of hyperthermia-induced changes in indices of systolic (lateral mitral annular S velocity) or diastolic function (lateral mitral annular E velocity, peak early diastolic filling and isovolumic relaxation time; P>0.05). However, with hyperthermia the global longitudinal systolic strain increased in the older group, but was unchanged in the young group (P=0.03). Also, older adults were unable to augment late diastolic ventricular filling [i.e. E/A ratio and A/(A+E) ratio] during hyperthermia, unlike the young (P<0.05). These findings indicate that older adults depend on a greater systolic contribution (global longitudinal systolic strain) to meet hyperthermic demand and that the atrial contribution to diastolic filling was not further augmented in older adults when compared with young adults.
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| 6. |
- Maliqueo, Manuel, et al.
(författare)
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Acupuncture does not ameliorate metabolic disturbances in the P450 aromatase inhibitor-induced rat model of polycystic ovary syndrome
- 2017
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Ingår i: Experimental Physiology. - : Wiley-Blackwell Publishing Ltd.. - 0958-0670 .- 1469-445X. ; 102:1, s. 113-127
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Tidskriftsartikel (refereegranskat)abstract
- Low-frequency electroacupuncture restores sex steroid synthesis and sympathetic activity in women with polycystic ovary syndrome, which may improve its metabolic disturbances likely by modulating sympathetic nerve activity or sex steroid synthesis. We investigated whether low-frequency electroacupuncture regulates the metabolic function to the same extent as treatment with estradiol or -adrenergic blocking in a rat model of polycystic ovary syndrome induced by a P450 aromatase inhibitor (letrozole). Letrozole (β00 μg per day) or placebo pellets were implanted in pre-pubertal Wistar rats. Six weeks thereafter, rats were treated for 5–6 weeks with: low-frequency electroacupuncture (5 days per week), a -adrenergic blocker (propranolol hydrochloride, 0.1 mg kg-1) (5 days per week), or 17-estradiol (β.0 μg) every fourth day. Body weight development, body composition, locomotor activity, insulin sensitivity, tissue specific glucose uptake, lipid profile, adipocyte size, adiponectin and insulin serum concentrations, and gene expression in inguinal fat were measured. All treatments increased circulating levels of LDL-cholesterol. Estradiol treatment restored locomotor activity and increased insulin sensitivity but did not modify the glucose uptake in muscle and fat. An upregulation of genes related to insulin sensitivity and downregulation of genes related to adipogenesis were observed in subcutaneous adipose tissue from rats exposed to letrozole. Only estradiol treatment normalized the expression of these genes. In conclusions, low-frequency electroacupuncture increased LDL-cholesterol without affecting the insulin sensitivity or adipose tissue function, which could suggest effects on hepatic lipid regulation probably mediated by estradiol action or -adrenergic pathway.
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| 7. |
- McDonnell, Adam C., et al.
(författare)
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The LunHab project : Muscle and bone alterations in male participants following a 10 day lunar habitat simulation.
- 2019
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Ingår i: Experimental Physiology. - : Wiley. - 0958-0670 .- 1469-445X. ; 104:8, s. 1250-1261
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Tidskriftsartikel (refereegranskat)abstract
- NEW FINDINGS: What is the central question of this study? It is well established that muscle and bone atrophy in conditions of inactivity or unloading, but there is little information regarding the effect of a hypoxic environment on the time course of these deconditioning physiological systems. What is the main finding and its importance? The main finding is that a horizontal 10 day bed rest in normoxia results in typical muscle atrophy, which is not aggravated by hypoxia. Changes in bone mineral content or in metabolism were not detected after either normoxic or hypoxic bed rest.ABSTRACT: Musculoskeletal atrophy constitutes a typical adaptation to inactivity and unloading of weightbearing bones. The reduced-gravity environment in future Moon and Mars habitats is likely to be hypobaric hypoxic, and there is an urgent need to understand the effect of hypoxia on the process of inactivity-induced musculoskeletal atrophy. This was the principal aim of the present study. Eleven males participated in three 10 day interventions: (i) hypoxic ambulatory confinement; (ii) hypoxic bed rest; and (iii) normoxic bed rest. Before and after the interventions, the muscle strength (isometric maximal voluntary contraction), mass (lean mass, by dual-energy X-ray absorptiometry), cross-sectional area and total bone mineral content (determined with peripheral quantitative computed tomography) of the participants were measured. Blood and urine samples were collected before and on the 1st, 4th and 10th day of the intervention and analysed for biomarkers of bone resorption and formation. There was a significant reduction in thigh and lower leg muscle mass and volume after both normoxic and hypoxic bed rests. Muscle strength loss was proportionately greater than the loss in muscle mass for both thigh and lower leg. There was no indication of bone loss. Furthermore, the biomarkers of resorption and formation were not affected by any of the interventions. There was no significant effect of hypoxia on the musculoskeletal variables. Short-term normoxic (10 day) bed rest resulted in muscular deconditioning, but not in the loss of bone mineral content or changes in bone metabolism. Hypoxia did not modify these results.
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| 8. |
- Nawrot-Porabka, K., et al.
(författare)
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The role of antisecretory factor in pancreatic exocrine secretion: Studies in vivo and in vitro
- 2015
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Ingår i: Experimental Physiology. - : Wiley. - 0958-0670 .- 1469-445X. ; 100:3, s. 267-277
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Tidskriftsartikel (refereegranskat)abstract
- New Findings: What is the central question of this study? Antisecretory factor, an endogenous protein detected in many tissues of the body, is known as an inhibitor of intestinal secretion, but its role in pancreatic exocrine secretory function has not yet been investigated. What is the main finding and its importance? In a rodent model, we show that antisecretory factor reduces pancreatic exocrine secretion, probably via its direct action on the pancreatic acini and via modulation of the enteropancreatic reflexes involving cholecystokinin and sensory nerves. Antisecretory factor (AF) regulates ion and water transport through the intestinal cell membrane. Antisecretory factor inhibits intestinal secretion, but its effect on the exocrine pancreas has not yet been shown. We investigated the effect of AF on pancreatic amylase secretion in vivo and in vitro using pancreatic acini isolated by collagenase digestion. For the in vivo study, Wistar rats were surgically equipped with silicone catheters, inserted into the pancreaticobiliary duct and into the duodenum. Capsaicin was used to deactivate the sensory nerves in turn to assess their involvement in the effects of AF on the exocrine pancreas. Antisecretory factor (1, 3 or 10 μg kg-1 i.p.) was given in basal conditions or following stimulation of pancreatic secretion with diversion of pancreaticobiliary juice. For the in vitro study, rat pancreatic acini were incubated in the presence of increasing doses of AF (from 10-8 to 10-5 m) alone or in combination with caerulein (10-12 m). Cytoplasmic cholecystokinin 1 (CCK1) receptor protein was detected by Western blot and immunoprecipitation studies. Antisecretory factor markedly reduced the output of pancreatic amylase both in basal conditions and when stimulated by diversion of pancreaticobiliary juice. Deactivation of the sensory nerves with capsaicin completely reversed the inhibitory effects of AF on the exocrine pancreas. Caerulein-induced enzyme secretion from the pancreatic acini was inhibited by AF, whereas basal secretion was unaffected. Administration of AF to the rats significantly diminished the synthesis of CCK1 receptor protein. We conclude that AF inhibits pancreatic exocrine secretion indirectly via sensory nerves and directly decreases amylase release from isolated pancreatic acini. The direct inhibitory action of AF on the exocrine pancreas could be related, at least in part, to a reduction of CCK1 receptors on pancreatic acinar cells.
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| 9. |
- Overgaard-Steensen, Christian, et al.
(författare)
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The frequently used intraperitoneal hyponatraemia model induces hypovolaemic hyponatraemia with possible model-dependent brain sodium loss
- 2016
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Ingår i: Experimental Physiology. - 0958-0670 .- 1469-445X. ; 101:7, s. 932-945
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Tidskriftsartikel (refereegranskat)abstract
- Hyponatraemia is common clinically, and if it develops rapidly, brain oedema evolves, and severe morbidity and even death may occur. Experimentally, acute hyponatraemia is most frequently studied in small animal models, in which the hyponatraemia is produced by intraperitoneal instillation of hypotonic fluids (I.P. model). This hyponatraemia model is described as 'dilutional' or 'syndrome of inappropriate ADH (SIADH)', but seminal studies contradict this interpretation. To confront this issue, we developed an I.P. model in a large animal (the pig) and studied water and electrolyte responses in brain, muscle, plasma and urine. We hypothesized that hyponatraemia was induced by simple water dilution, with no change in organ sodium content. Moderate hypotonic hyponatraemia was induced by a single I.V. dose of desmopressin and intraperitoneal instillation of 2.5% glucose. All animals were anaesthetized and intensively monitored. In vivo brain and muscle water was determined by magnetic resonance imaging and related to the plasma sodium concentration. Muscle water content increased less than expected as a result of pure dilution, and muscle sodium content decreased significantly (by 28%). Sodium was redistributed to the peritoneal fluid, resulting in a significantly reduced plasma volume. This shows that the I.P. model induces hypovolaemic hyponatraemia and not dilutional/SIADH hyponatraemia. Brain oedema evolved, but brain sodium content decreased significantly (by 21%). To conclude, the I.P. model induces hypovolaemic hyponatraemia attributable to sodium redistribution and not water dilution. The large reduction in brain sodium is probably attributable to the specific mechanism that causes the hyponatraemia. This is not accounted for in the current understanding of the brain response to acute hyponatraemia.
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| 10. |
- Siebenmann, Christoph, et al.
(författare)
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Does cerebral hypoxia facilitate central fatigue?
- 2016
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Ingår i: Experimental Physiology. - : IEEE Press. - 0958-0670 .- 1469-445X. ; 101:9, s. 1173-1177
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Tidskriftsartikel (refereegranskat)abstract
- New Findings: What is the topic of this review? This review addresses whether a mismatch between cerebral O2 demand and delivery accelerates the development of central fatigue during endurance-type exercise. What advances does it highlight? The difficulty with studying the importance of cerebral O2 availability for exercise performance is to manipulate cerebral O2 availability independently of muscular O2 availability. The different approaches to overcome this limitation indicate that cerebral oxygenation is not a major limiting factor in normoxia, but may limit performance in submaximal exercise tasks in hypoxia. Central fatigue originates within the central nervous system and is characterized by a decrease in voluntary muscle activation. Reduced systemic O2 availability can facilitate central fatigue by enhancing the afferent input of the chemosensitive nerves that play a pivotal role in development of central fatigue. There is accumulating evidence that, in some situations, inadequate O2 availability to the brain itself promotes central fatigue. This short review presents some of the recent findings supporting a direct effect of inadequate cerebral O2 availability on central fatigue and addresses the persisting limitations.
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| 11. |
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| 12. |
- Sotiridis, Alexandros, et al.
(författare)
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Heat acclimation does not affect maximal aerobic power in thermoneutral normoxic or hypoxic conditions
- 2019
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Ingår i: Experimental Physiology. - 0958-0670 .- 1469-445X. ; 104, s. 1250-1261
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Tidskriftsartikel (refereegranskat)abstract
- What is the central question of this study? Controlled-hyperthermia heat acclimation protocols induce an array of thermoregulatory and cardiovascular adaptations that facilitate exercise in hot conditions. We investigated whether this ergogenic potential can be transferred to thermoneutral normoxic or hypoxic exercising conditions. What is the main finding and its importance? We show that heat acclimation did not affect maximal cardiac output or maximal aerobic power in thermoneutral normoxic/hypoxic conditions. Heat acclimation augmented the sweating response in thermoneutral normoxic conditions. The cross-adaptation theory according to which heat acclimation could facilitate hypoxic exercise capacity is not supported by our data. ABSTRACT: Heat acclimation (HA) mitigates heat-induced decrements in maximal aerobic power (V̇O2peak ) and augments exercise thermoregulatory responses in the heat. Whether this beneficial effect of HA is observed in hypoxic or thermoneutral conditions remains unresolved. We explored the effects of HA on exercise cardiorespiratory and thermoregulatory responses in normoxic, hypoxic, and hot conditions. Twelve males (V̇O2peak 54.7(5.7) mL·kg-1 ·min-1 ) participated in a HA protocol comprising 10 daily 90-min controlled-hyperthermia (target rectal temperature, Tre = 38.5 °C) exercise sessions. Before and after HA, we determined V̇O2peak in thermoneutral normoxic (NOR), thermoneutral hypoxic (13.5% Fi O2 ; HYP) and hot (35 °C, 50% RH; HE) conditions in a randomized and counterbalanced order. Preceding each maximal cycling test, a 30-min steady-state exercise at 40% of the NOR peak power output (Wpeak ) was employed to evaluate thermoregulatory responses. HA induced the expected adaptations in HE: reduced Tre and submaximal heart rate (HR), enhanced sweating response and expanded plasma volume. However, HA did not affect V̇O2peak or maximal cardiac output (COmax ) (P = 0.61). Wpeak was increased post-HA in NOR (P < 0.001) and HE (P < 0.001) by 41 ± 21 and 26 ± 22 W, respectively but not in HYP (P = 0.14). Gross mechanical efficiency was higher (P = 0.004) whereas resting Tre and sweating thresholds were lower (P < 0.01) post-HA across environments. Nevertheless, the gain of the sweating response decreased (P = 0.05) in HYP. In conclusion, our data do not support a beneficial cross-over effect of HA on V̇O2peak in normoxic or hypoxic conditions. This article is protected by copyright.
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| 13. |
- Tarum, Janelle, 1991-, et al.
(författare)
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Electrical pulse stimulation : an in vitro exercise model for the induction of human skeletal muscle cell hypertrophy. A proof-of-concept study
- 2017
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Ingår i: Experimental Physiology. - : John Wiley & Sons. - 0958-0670 .- 1469-445X. ; 102:11, s. 1405-1413
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Tidskriftsartikel (refereegranskat)abstract
- New Findings:What is the central question of this study?Is electrical pulse stimulation (EPS) an in vitro exercise model able to elicit the hypertrophy of human muscle cells?What is the main finding and its importance?The addition of a restitution period of 8h after EPS induces the enlargement of human muscle cells, a major physiological end-point to resistance exercise. This is supported by downregulationof myostatin, a negative regulator of muscle mass, and increased phosphorylated mTOR and 4E-BP1, key factors in the growth cascade. This proof-of-concept study provides a model of physiologically mediated muscle growth, which will be the basis for future studies aiming to depict molecular events governing the hypertrophy of human muscle cells.Electrical pulse stimulation (EPS) of muscle cells has previouslybeenused as an in vitro exercise model. The present study aimedto establish an EPS protocol promoting the hypertrophy ofhuman muscle cells, which represents a major physiological end-point to resistance exercise in humans. We hypothesized that adding a resting period after EPS would be crucial for the occurrence of the morphological change. Myoblasts obtained from human muscle biopsies (n=5) were differentiated into multinucleated myotubes and exposed to 8h of EPS consisting of 2ms pulses at 12V, with a frequency of 1Hz. Myotube size was assessed using immunohistochemistry immediately, 4 and 8h after completed EPS. Gene expression and phosphorylation status of selected markers of hypertrophy were assessed using RT-PCR and Western blotting, respectively. Release of the myokine interleukin-6 in culture medium was measured using enzyme-linked immunosorbent assay. We demonstrated a significant increase (31 +/- 14%; P=0.03) in the size of myotubes when EPS was followed by an 8h resting period, but not immediately or 4h after completion of EPS. The response was supported by downregulation (P=0.04) of the gene expression of myostatin, a negative regulator of muscle mass, and an increase in phosphorylated mTOR (P=0.03) and 4E-BP1 (P=0.01), which are important factors in the cellular growth signalling cascade. The present work demonstrates that EPS is an in vitro exercise model promoting the hypertrophy of human muscle cells, recapitulating a major physiological end-point to resistance exercise in human skeletal muscle.
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| 14. |
- Wan Saudi, Wan Salman, et al.
(författare)
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Short-chain fatty acids augment rat duodenal mucosal barrier function
- 2017
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Ingår i: Experimental Physiology. - 0958-0670 .- 1469-445X. ; 102:7, s. 791-803
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Tidskriftsartikel (refereegranskat)abstract
- Short-chain fatty acids (SCFAs) are produced by bacterial fermentation in the large intestine, particularly from diets containing fibres and carbohydrates. The small intestinal epithelium is exposed to SCFAs derived mainly from oral bacteria or food supplementation. Although luminal nutrients are important in regulation of intestinal functions, the role of SCFAs in regulation of small intestinal mucosal barrier function and motility has not been fully described. The aim of the present study was to elucidate the effects of acetate and propionate on duodenal mucosal barrier function and motility. Rats were anaesthetized with thiobarbiturate, and a 30 mm segment of proximal duodenum with an intact blood supply was perfused. The effects on duodenal bicarbonate secretion, blood-to-lumen clearance of Cr-51-EDTA, motility and transepithelial net fluid flux were investigated. Perfusion of the duodenum with acetate or propionate significantly decreased mucosal paracellular permeability and transepithelial net fluid flux and significantly increased bicarbonate secretion. Acetate or propionate administered as an I.V. infusion decreased the mucosal paracellular permeability, but significantly decreased bicarbonate secretion. Luminal SCFAs changed the duodenal motility pattern from migrating motor complexes to fed patterns. Systemic administration of glucagon-like peptide-2 induced increases in both bicarbonate secretion and net fluid absorption, but did not change motility. Glucagon-like peptide-2 infusion during luminal perfusion of SCFAs significantly reduced the motility. In conclusion, SCFAs decreased duodenal paracellular permeability and net fluid flux. Short-chain fatty acids induced opposite effects on bicarbonate secretion after luminal and i.v. administration. Presence of SCFAs in the lumen induces fed motility patterns. Altered luminal chemosensing and aberrant signalling in response to SCFAs might contribute to symptoms observed in patients with suppressed barrier function.
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| 15. |
- Cui, Peng, et al.
(författare)
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Hypothalamic DNA methylation in rats with dihydrotestosterone-induced polycystic ovary syndrome: effects of low-frequency electro-acupuncture.
- 2018
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Ingår i: Experimental physiology. - 1469-445X. ; 103:12, s. 1618-1632
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Tidskriftsartikel (refereegranskat)abstract
- What is the central question of this study? What is the role of hypothalamic DNA methylation in the development of PCOS and the response to electro-acupuncture treatment. What is the main finding and its importance? Global DNA methylation and expression of DNA methyltransferases (Dnmts) were increased in PCOS-like rats, and electro-acupuncture decreased global DNA methylation and Dnmt3b expression. Pyrosequencing showed that the DNA methylation of some PCOS candidate genes was changed in the PCOS and PCOS+EA groups, suggesting that hypothalamic DNA methylation plays an important role in the development of PCOS and in mediating the effects of electro-acupuncture treatment.Polycystic ovary syndrome (PCOS) is a common reproductive and endocrine disease of unknown etiology. Recently, epigenetic studies focusing on DNA methylation in PCOS have received much attention, but the mechanisms are still unclear. In the present study, we used the 5a-dihydrotestosterone-induced PCOS-like rat model and treated the rats with electro-acupuncture (EA). Rats were randomly divided into four groups - controls, diet-induced obesity (DIO), PCOS, and PCOS+EA. We examined the reproductive, metabolic, and behavioral phenotypes, validated the effect of EA, and explored the role of hypothalamic DNA methylation by analyzing the methylation of global DNA and selected candidate genes. The PCOS rats presented with reproductive dysfunctions such as lack of regular estrus cyclicity, metabolic disorders such as increased body weight and insulin resistance, and depression and anxiety-like behaviors. EA improved the reproductive functions, decreased body weight, and improved experimental depressive behavior. Furthermore, global DNA methylation and the expression of DNA methyltransferases (Dnmts) were increased in PCOS rats compared to the control group, and EA decreased the global DNA methylation and the expression of Dnmt3b. In addition, pyrosequencing showed that the DNA methylation of certain CpG sites in targeted genes (Plcg1, Camk2b, Esr2, and Pgr) was increased in the PCOS group, but the DNA methylation of Camk2b and Ar was decreased after EA treatment. These results indicate that hypothalamic DNA methylation might be correlated with the development of PCOS and that EA has an effect on hypothalamic DNA methylation in PCOS rats. This article is protected by copyright. All rights reserved.
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| 16. |
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| 17. |
- Joyner, M. J., et al.
(författare)
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Sex differences and blood pressure regulation in humans
- 2016
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Ingår i: Experimental Physiology. - : Wiley. - 0958-0670. ; 101:3, s. 349-355
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Tidskriftsartikel (refereegranskat)abstract
- New Findings What is the topic of this review? Over the past decade, our team has investigated interindividual variability in human blood pressure regulation. What advances does it highlight? In men, we have found a tight relationship between indices of sympathetic activity and vascular resistance across the age span. This relationship is absent in young women but seen in postmenopausal women. These sex and age differences in vascular resistance are largely a result of changes in the balance of vasodilating and vasoconstricting adrenergic receptor tone. When these changes are considered along with cardiac output, a coherent picture is beginning to emerge of why blood pressure rises more with age in women than men. Arterial pressure is a key regulated variable in the cardiovascular system with important health implications. Over the last 12years, we have used physiological measurements, including muscle sympathetic nerve activity (MSNA), to explore the balance among mean arterial blood pressure, cardiac output and total peripheral resistance (TPR) in normotensive humans. We have shown that these determinants of blood pressure can vary widely in different subjects and how they vary depends on sex and age. In young men, there is a direct relationship between MSNA and TPR but no relationship with blood pressure. This is because cardiac output is proportionally lower in those with high MSNA and TPR. In contrast, in young women there is no relationship between MSNA and TPR (or cardiac output); this is because -adrenergic vasodilator mechanisms offset -adrenergic vasoconstriction. Thus, blood pressure is unrelated to MSNA in young women. In older women, -adrenergic vasodilator mechanisms are diminished, and a direct relationship between MSNA and TPR is seen. In older men, the relationships among these variables are less clear cut, perhaps owing to age-related alterations in endothelial function. With ageing, the relationship between MSNA and blood pressure becomes positive, more so in women than in men. The finding that the physiological control of blood pressure is so different in men and women and that it varies with age suggests that future studies of mechanisms of hypertension will reveal corresponding differences among groups.
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| 20. |
- Lozinska, Liudmyla, et al.
(författare)
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Decreased insulin secretion and glucose clearance in exocrine pancreas-insufficient pigs.
- 2016
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Ingår i: Experimental Physiology. - 1469-445X. ; 101:1, s. 100-112
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Tidskriftsartikel (refereegranskat)abstract
- What is the central question of this study? Does the exocrine pancreas have an impact on endocrine pancreatic function and peripheral nutrient utilization? What is the main finding and its importance? In an exocrine pancreas-insufficient pig model, the insulin response to a glucose load was delayed. Oral enzyme supplementation did not improve the insulin release but facilitated blood glucose clearance. These results suggest an acino-insular axis communication affecting islet function and an impact of gut pancreatic enzymes on blood glucose utilization. The effect of exocrine pancreatic function on the glucose-mediated insulin response and glucose utilization were studied in an exocrine pancreas-insufficient (EPI) pig model. Five 10-week-old EPI pigs after pancreatic duct ligation and 6 age-matched, non-operated control pigs were used in the study. Blood glucose, plasma insulin and C-peptide concentrations were monitored during meal (MGTT), oral (OGTT) and intravenous (IVGTT) glucose tolerance tests. Upon post-mortem examination, the pancreatic remnants of the EPI pigs showed acinar fibrotic atrophy but normal islets and β-cell morphology. The EPI pigs displayed increased fasting glucose concentrations compared with control animals (6.4 ± 0.4 versus 4.8 ± 0.1 mmol l(-1) , P < 0.0001) but unchanged insulin concentrations (2.4 ± 0.6 versus 2.1 ± 0.2 pmol l(-1) ). During the OGTT and IVGTT, the EPI pigs showed slower, impaired glucose utilization, with the disruption of a well-timed insulin response. Plasma C-peptide concentrations confirmed the delayed insulin response during the IVGTT in EPI pigs. Oral pancreatic enzyme supplementation (PES) of EPI pigs improved glucose clearance during IVGTT [AUCglucose 1295 ± 70 mmol l(-1) × (120 min) in EPI versus 1044 ± 32 mmol l(-1) × (120 min) in EPI + PES, P < 0.0001] without reinforcing the release of insulin [AUCC-peptide 14.4 ± 3.8 nmol l(-1) × (120 min) in EPI versus 6.4 ± 1.3 nmol l(-1) × (120 min) in EPI + PES, P < 0.002]. The results suggest the existence of an acino-insular axis regulatory communication. The presence of pancreatic enzymes in the gut facilitates glucose utilization in an insulin-independent manner, indicating the existence of a gut-derived pancreatic enzyme-dependent mechanism involved in peripheral glucose utilization.
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| 21. |
- Montero, D., et al.
(författare)
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Sexual dimorphism of substrate utilization: Differences in skeletal muscle mitochondrial volume density and function
- 2018
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Ingår i: Experimental Physiology. - : Wiley. - 0958-0670. ; 103:6, s. 851-859
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Tidskriftsartikel (refereegranskat)abstract
- Fat oxidation during exercise is greater in females than in males. We sought to determine whether sex differences in substrate metabolism are paralleled by distinct skeletal muscle mitochondrial volume density and oxidative capacity. Whole-body substrate (fat and carbohydrate) utilization during submaximal treadmill running was assessed, and skeletal muscle biopsies were taken to determine mitochondrial volume density and function in healthy young females (n=12) and males (n=12) matched by aerobic exercise capacity and exercise performance. Females presented a lower respiratory exchange ratio (0.87 +/- 0.04 versus 0.91 +/- 0.04, P=0.023) and whole-body carbohydrate oxidation (27.8 +/- 8.3 versus 35.8 +/- 6.5mgkg(-1)min(-1), P=0.027), whereas fat oxidation was higher (8.7 +/- 2.8 versus 5.9 +/- 2.6mgkg(-1)min(-1), P=0.034) during submaximal exercise compared with males. In skeletal muscle biopsies, females demonstrated augmented mitochondrial volume density (7.51 +/- 1.77 versus 5.90 +/- 1.72%, P=0.035) and oxidative capacity for fatty acid [36.6 +/- 12.8 versus 24.5 +/- 7.3pmol O(2)s(-1)(mg wet weight)(-1), P=0.009] and lactate [71.1 +/- 24.4 versus 53.2 +/- 14.6pmol O(2)s(-1)(mg wet weight)(-1), P=0.040]. No sex differences in respiratory exchange ratio, whole-body fat oxidation and skeletal muscle variables were detected when adjusted for anthropometric variables including body mass or leg mass, which were lower in females. In conclusion, female prioritization of fat over carbohydrate oxidation during exercise is underpinned by augmented body size-related mitochondrial volume density, fatty acid and lactate oxidative capacity in skeletal muscle fibres.
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| 22. |
- Sotak, M., et al.
(författare)
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Putative tissue location and function of the SLC5 family member SGLT3
- 2017
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Ingår i: Experimental Physiology. - : Wiley. - 0958-0670. ; 102:1, s. 5-13
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Tidskriftsartikel (refereegranskat)abstract
- New Findings What is the topic of this review? This review summarizes the evidence on the localization, electrophysiological properties, agonist specificity and putative physiological role of sodium-glucose transporter 3 (SGLT3). What advances does it highlight? Published information is reviewed in some detail by comparing human and rodent isoforms, as well as advances in testing hypotheses for the physiological role of SGLT3 as a glucose sensor or incretin release mediator. We provide a critical overview of available published data and discuss a putative functional role for SGLT3 in human and mouse physiology. Sodium-glucose transporter 3 (SGLT3) has attracted interest because of its putative role as a glucose sensor, rather than a sugar transporter, in contrast to its co-family members SGLT1 and SGLT2. Significant progress has been made in characterizing the electrophysiological properties in vitro of the single human SGLT3 isoform and the two mouse isoforms, SGLT3a and SGLT3b. Although early reports indicated SGLT3 expression in the small intestinal myenteric and submucosal neurones, hypothalamic neurones, portal vein and kidney, a lack of reliable antibodies has left unanswered its exact tissue and cellular localization. Several hypotheses for a role of SGLT3 in glucose sensing, gastric emptying, glucagon-like peptide-1 release and post-Roux-en-Y gastric bypass remodelling have been explored, but so far there is only limited and indirect supportive evidence using non-specific agonists/antagonists, with no firm conclusions. There are no published or available data in knockout animals, and translation is difficult because of its different isoforms in human versus rodent, as well as a lack of selective agonists or antagonists, all of which make SGLT3 challenging to study. However, its unique electrophysiological properties, ubiquitous expression at the mRNA level, enrichment in the small intestine and potential, but uncertain, physiological role demand more attention. The purpose of this overview and review of SGLT3 biology is to provide an update, highlight the gaps in our knowledge and try to signpost potential ways forward to define its likely function in vivo.
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