Experimental Physiology最新文献

{"title":"The mood stabilizers lithium and valproate disrupt hepatic and intestinal farnesoid X receptor signalling and increase bile synthesis in the rat.","authors":"Sofia Cussotto, Anna V Golubeva, Alvaro Lopez Gallardo, Thomaz F S Bastiaanssen, Alexander V Zhdanov, Gerard M Moloney, Caitriona Scaife, Jane A English, Susan A Joyce, Timothy G Dinan, John F Cryan","doi":"10.1113/EP092451","DOIUrl":"https://doi.org/10.1113/EP092451","url":null,"abstract":"<p><p>The mood stabilizers lithium and valproate are psychotropic medications widely used in clinical practice. Despite their proven benefits, many individuals stop their treatment due to the adverse effects. Chronic diarrhoea is a common reason for discontinuation of these drugs; however, the underlying mechanisms are unknown. Excessive loss of bile acids (BA) into the colon is a major cause of diarrhoea. Therefore, we aimed to investigate the effects of these drugs on BA metabolism. We measured BA levels in the liver, plasma and faeces of Sprague-Dawley rats treated with lithium or valproate for 4 weeks. Next, we analysed changes in the expression of genes and proteins involved in BA production and enterohepatic circulation. Lithium and valproate markedly increased BA levels across all body sites. This was accompanied by the up-regulation of hepatic cytochrome P450 7A1 (Cyp7a1), the rate-limiting enzyme in de novo BA synthesis. Under normal conditions, elevated levels of BAs suppress Cyp7a1 via activation of the hepatic farnesoid X receptor (Fxr)/small heterodimer partner (Shp) and intestinal Fxr/fibroblast growth factor 19 (Fgf19) pathways. This signalling was disrupted in both treatment groups. The Fxr-mediated responses in the expression of Ntcp, Asbt, Ilbp and Ostα/β bile transporters were also affected by treatment. In conclusion, lithium and valproate disrupted farnesoid X receptor signalling at the hepatic and intestinal levels, inducing sustained overproduction of bile in rats. These findings provide novel insights into the peripheral effects of these drugs. Given that similar changes in bile circuits underlie the pathophysiology of primary BA diarrhoea in humans, this study suggests a potential mechanism behind chronic diarrhoea in patients undergoing lithium or valproate therapy.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac conduction system and the electrocardiogram of the common hippopotamus (Hippopotamus amphibius).","authors":"Morten B Thomsen, Peter Agger, Henrik Lauridsen, Vibeke Sødring Elbrønd, Camilla Rensch Davidsen, Emma Smedsgaard Byskov, Frederik Stig Scharling, Tobias Wang, Sara Andreia Rodrigues Abreu, Stamatios Alan Tahas, Carsten Grøndahl, Mads Frost Bertelsen, Kirstine Calloe","doi":"10.1113/EP092519","DOIUrl":"https://doi.org/10.1113/EP092519","url":null,"abstract":"<p><p>The common hippopotamus (Hippopotamus amphibius) shares a common terrestrial ancestor with whales (Cetacea) and has independently evolved similar physiological adaptations to their aquatic lifestyle. Although several studies have explored the electrical signalling in whale hearts, the understanding of the conduction system and electrical activation of the hippopotamus heart remains sparse. We set out to map the conduction system within the hippopotamus heart and determine the sequence of electrical activation, including the mean electrical axis of ventricular activation. ECGs were recorded from three anaesthetized hippopotamuses. Histological samples were collected from two of these animals and from an additional animal. The hearts of the hippopotamuses constituted ∼0.3% of body mass and as in whales, the hearts were situated more cranially in the thoracic cavity compared to most terrestial mammals, and were spanning from the first to the fourth intercostal space. The network of Purkinje fibre strands extended deep into the ventricular walls and consisted of large, ovoid cells. Orthogonal ECG recordings revealed a mean electrical axis pointing towards the neck of the animal, indicating that electrical activation takes place in an apex-to-base direction.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Durability as an index of endurance exercise performance: Methodological considerations.","authors":"Ben Hunter, Ed Maunder, Andrew M Jones, Gabriele Gallo, Daniel Muniz-Pumares","doi":"10.1113/EP092120","DOIUrl":"https://doi.org/10.1113/EP092120","url":null,"abstract":"<p><p>Endurance athletes routinely complete physiological assessments to predict performance, inform training programmes and monitor subsequent training adaptations. This profiling is typically performed with the athlete in a 'fresh' (i.e., rested) condition, but physiological profiling variables deteriorate during prolonged exercise. Durability has been defined as the resilience to the deterioration of physiological variables and performance during or following prolonged exercise. Herein, we review the current approaches to measure durability. The construction of the fatiguing protocol affects durability profiles, with greater relative intensity and duration resulting in more marked deterioration of baseline measures. The design of durability assessments should control for factors that could impact durability measurements, such as nutrition and environmental characteristics, to ensure that outcomes are repeatable and can be compared between athletes or over time in the same athlete. The selection of these parameters should be based on the proposed research question or applied context and take account of the training status of the athlete. Accordingly, this review highlights important considerations to ensure that protocols for profiling durability in research and applied practice are appropriate.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myths and methodologies: Invasive and non-invasive assessment of respiratory muscle activity in humans.","authors":"Anna L Hudson, Caroline J Jolley, Simon C Gandevia, Jane E Butler","doi":"10.1113/EP091526","DOIUrl":"https://doi.org/10.1113/EP091526","url":null,"abstract":"<p><p>Survival relies on neural respiratory drive from the medullary respiratory centres to activate the respiratory muscles for breathing. Accurate assessment of respiratory muscle activity, as an estimate of neural respiratory drive in humans, will facilitate a greater understanding of respiratory physiology, the pathophysiology of diseases and injuries, clinical investigations and the neurophysiology of breathlessness perception. Here, we highlight the methodologies to measure respiratory muscle activity, their appropriate application, the potential limitations of the data and their safety and feasibility considerations. These recommendations can be applied to all skeletal muscles.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of acute caffeine intake on local tolerance to cold before and after total sleep deprivation.","authors":"Baptiste de Lorgeril, Pierre-Emmanuel Tardo-Dino, Cyprien Bourrilhon, Michael Quiquempoix, Catherine Drogou, Lise Mateo, Mégane Erblang, Philippe Colin, Pascal Van Beers, Mounir Chennaoui, Danielle Gomez-Merino, Fabien Sauvet","doi":"10.1113/EP092356","DOIUrl":"https://doi.org/10.1113/EP092356","url":null,"abstract":"<p><p>Total sleep deprivation (TSD) alters local cold tolerance and could thus increase the risk of cold injury. We evaluated the impact of acute caffeine intake, the main countermeasure to TSD-related deleterious effects, on local cold tolerance before and after TSD. Thirty-six healthy subjects underwent two TSD protocols (i.e., continuous wakefulness), with randomized crossover intake of acute caffeine or placebo (2.5 mg/kg) administered twice during wakefulness. Before and after 33 h of TSD, finger (index and annular) temperature and skin blood flow were assessed during cold-water immersion (CWI, 5°C, 20 min) followed by 20 min of rewarming in ambient air. We showed no significant effects of TSD on mean finger temperature during CWI in the placebo condition, but a significant reduction of the minimal temperature (8.86°C ± 0.35°C vs. 8.64°C ± 0.27°C, p = 0.02). During rewarming, we showed a reduction in temperature in the placebo condition (p = 0.02 for the mean temperature and p = 0.03 for the maximal) and an increase in the skin blood flow disparity between fingers at the four points of laser speckle rewarming measurements (p = 0.03). After TSD, acute caffeine intake (vs. placebo) increased mean (+2.11°C ± 0.21°C, p = 0.01) and minimal (+0.61°C ± 0.10°C, p = 0.02) finger temperatures during CWI, and improved rewarming after CWI (mean and maximal temperatures) (+2.28°C ± 0.08°C, p = 0.01, and +2.06°C ± 0.12°C, p = 0.02, respectively). Before TSD, acute caffeine intake significantly increased (vs. placebo) mean temperatures during CWI (p = 0.03) and reduced pain from the onset (p = 0.03) to the end of CWI (p = 0.02) and the first 2 min of rewarming (p = 0.04). There was also a significant main effect of habitual daily caffeine consumption on minimal finger temperatures during CWI, which decreased significantly between 0 and 600 mg consumption (R² = -0.43, p = 0.01), independently of the effects of day (before and after TSD) and treatment (caffeine and placebo conditions). These findings suggest that acute caffeine intake could be a protective countermeasure to local cold tolerance, particularly during TSD. However, habitual daily caffeine consumption is a factor of individual variability that should be recorded during CWI protocols. Clinical trial NCT03859882.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Earth to orbit: How to preserve muscle health in space and bed rest.","authors":"Antonios Matsakas, Colleen Deane","doi":"10.1113/EP092729","DOIUrl":"https://doi.org/10.1113/EP092729","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the exercise-related kinetics of circulating cell-free DNA, circulating tumour DNA, DNase I activity and cytokines in patients with solid tumours: A pilot study.","authors":"Elmo W I Neuberger, Alexandra Brahmer, Tobias Ehlert, Suzan Botzenhardt, Alfonso De Falco, Birgit Enders, Patricia S Hähnel, Achim Heintz, Carl C Schimanski, Thomas Kindler, Perikles Simon","doi":"10.1113/EP092167","DOIUrl":"https://doi.org/10.1113/EP092167","url":null,"abstract":"<p><p>Circulating cell-free DNA (cfDNA), circulating tumour DNA (ctDNA) and inflammatory cytokines have prognostic and predictive value in oncology. However, the effects of acute exercise on cfDNA levels are unknown. Here, we explore the kinetics of cfDNA, ctDNA and cytokines upon an incremental exercise test in a pilot cohort of cancer patients compared with healthy control subjects. Patients with solid tumours (n = 12) and age-matched control subjects (n = 6) were recruited to perform an all-out cardiopulmonary bicycle test. Blood samples were collected before (Pre), directly after (Post) and 90 min after the test (+90 min), and the cfDNA, ctDNA (Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations), DNase I activity and cytokine levels were measured. Cardiopulmonary exercise testing was easily feasible in cancer patients, and data from eight patients and five control subjects were available for exploratory statistical evaluation. The cfDNA levels increased from Pre to Post and decreased to baseline at +90 min in all subjects. The cfDNA concentrations and DNase I activity were clearly correlated in the control but not in the cancer group. Neutrophil-associated myeloperoxidase (MPO), calprotectin (MRP 8/14), and lipocalin A (NGAL) showed strong responses to exercise. The percentage of ctDNA, detected in only one cancer patient, decreased after acute exercise. In our study, we could safely perform cardiopulmonary exercise testing with patients with different cancer entities and subsequently run biomarker analyses. Our results hint at an exercise-triggered release of cfDNA and neutrophil-derived cytokines in cancer patients.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological sex does not impact intrinsic mitochondrial respiration supported by complexes I and II in human skeletal muscle.","authors":"Emily J Ferguson, Lauren J Pacitti, Justin Bureau, Callum J Pufahl, Eveline Menezes, Tanner Stokes, Shivam Gandhi, Luca J Delfinis, Craig A Simpson, Christopher G R Perry, Brendon J Gurd, Chris McGlory","doi":"10.1113/EP092551","DOIUrl":"https://doi.org/10.1113/EP092551","url":null,"abstract":"<p><p>The effect of biological sex on rates of skeletal muscle mitochondrial respiration supported by creatine-dependent phosphate shuttling was previously unknown. The aim of this investigation was to test the hypothesis that females and males matched for peak oxygen uptake normalized to fat-free mass would not exhibit differences in rates of mass-specific and intrinsic mitochondrial respiration in the presence or absence of creatine. Rates of mass-specific and intrinsic complex I (pyruvate and malate)- and complex I+II-supported, adenosine diphosphate (ADP)-stimulated mitochondrial respiration in the presence and absence of 20 mM creatine were measured via high-resolution respirometry. Total, intermyofibrillar and subsarcolemmal mitochondrial volume density were analysed using transmission electron microscopy. Rates of intrinsic mitochondrial respiration were obtained by normalizing mass-specific respiration rates to total mitochondrial volume density and total electron transport chain subunit protein content. Overall, there was no effect of sex on rates of mass-specific or intrinsic mitochondrial respiration in the presence or absence of creatine. There was also no effect of sex on total, intermyofibrillar and subsarcolemmal mitochondrial volume density or electron transport chain subunit protein content. Our data demonstrate an overall lack of sex-based differences in rates of intrinsic complex I- and complex I+II-supported, ADP-stimulated mitochondrial respiration in the presence or absence of creatine in females and males matched for aerobic fitness. Thus, biological sex per se does not appear to modulate intrinsic skeletal muscle mitochondrial respiration in healthy young adults.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On the measurement of glomerular filtration rate: An odyssey into the milieu intérieur.","authors":"Anders Møller Greve, Anna Agnes Lytzen, Hrefna Sæunn Einarsdóttir, Michael Perch, Ronan M G Berg","doi":"10.1113/EP092699","DOIUrl":"https://doi.org/10.1113/EP092699","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The unspecific control of cardiac output during exercise and in (patho-)physiology: Time to get more specific!","authors":"Eric J. Stöhr","doi":"10.1113/EP092578","DOIUrl":"10.1113/EP092578","url":null,"abstract":"&lt;p&gt;Ever since William Harvey's conclusion in 1628 that the volume of blood passing through the arteries could not be produced continuously by the liver but that, instead, blood had to be ‘circulating’, cardiac output has become one of the fundamental variables in physiology (Carty, &lt;span&gt;2016&lt;/span&gt;). It has been implicated in the matching of an increased O&lt;sub&gt;2&lt;/sub&gt; demand during exercise, plays an important role in the prevailing blood pressure, and is a major factor when considering cardiovascular disease, for example during heart failure (Bada et al., &lt;span&gt;2012&lt;/span&gt;; Edward et al., &lt;span&gt;2023&lt;/span&gt;; Magder, &lt;span&gt;2018&lt;/span&gt;). Since cardiac output is the product of heart rate and stroke volume, it could be expected that the two factors will be controlled interdependently to arrive at a specific cardiac output (Stöhr, &lt;span&gt;2022&lt;/span&gt;). Support for this thinking has been provided by a study that has shown that atrial pacing above an individual's heart rate did not increase cardiac output during exercise (Munch et al., &lt;span&gt;2014&lt;/span&gt;). Furthermore, peripheral vasodilatation via ATP infusion or heat stress has been said to determine a specific cardiac output, suggesting that cardiac output is a responder to peripheral flow (Bada et al., &lt;span&gt;2012&lt;/span&gt;; Watanabe et al., &lt;span&gt;2024&lt;/span&gt;). However, some gaps in our knowledge remain. For example, increasing the heart's chronotropy via atrial pacing without concomitant sympathetic stimulation will remove the typical influence on myocardial contractility and vasomotor tone. Equally, peripheral vasodilatation via ATP is insightful but does not represent the in vivo effects of peripheral vasodilatation caused by simultaneous neurohormonal control. Therefore, previous findings may not be transferrable to the natural in vivo regulation. And while the relationship between cardiac output and peripheral flow as a result of heat stress is undisputed, it remains unclear whether cardiac output determines the peripheral flow or vice versa. Far from being a trivial matter, a few scenarios are thinkable: an increased peripheral flow could be caused by (1) rate-induced changes in the frequency of cardiac ejection, (2) volume-induced changes by enhanced stroke volume of the heart, or (3) volume-induced regulation by peripheral vasodilatation. While the latter scenario is most likely the initiator via rapid, local dilatation of the microcirculation of the skin or the skeletal muscle capillaries involving gap junctions composed of Cx40 (Kowalewska et al., &lt;span&gt;2024&lt;/span&gt;), most recent studies have not been able to detect a significant change in the proximal conduit artery diameter (Watanabe et al., &lt;span&gt;2024&lt;/span&gt;). Until the beat-by-beat time course of events along the O&lt;sub&gt;2&lt;/sub&gt; cascade is shown, empirical evidence for scenario (3) remains theoretical. Coupled with the aforementioned doubt that cardiac output is indeed specific and ‘matches’ the peripheral demand (and flow) via coordinated cont","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":"110 5","pages":"631-633"},"PeriodicalIF":2.6,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1113/EP092578","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}