Acta Physiologica最新文献

{"title":"The role of the mesangium in glomerular function","authors":"Roberto Boi,&nbsp;Kerstin Ebefors,&nbsp;Jenny Nyström","doi":"10.1111/apha.14045","DOIUrl":"10.1111/apha.14045","url":null,"abstract":"<p>When discussing glomerular function, one cell type is often left out, the mesangial cell (MC), probably since it is not a part of the filtration barrier per se. The MCs are instead found between the glomerular capillaries, embedded in their mesangial matrix. They are in direct contact with the endothelial cells and in close contact with the podocytes and together they form the glomerulus. The MCs can produce and react to a multitude of growth factors, cytokines, and other signaling molecules and are in the perfect position to be a central hub for crosstalk communication between the cells in the glomerulus. In certain glomerular diseases, for example, in diabetic kidney disease or IgA nephropathy, the MCs become activated resulting in mesangial expansion. The expansion is normally due to matrix expansion in combination with either proliferation or hypertrophy. With time, this expansion can lead to fibrosis and decreased glomerular function. In addition, signs of complement activation are often seen in biopsies from patients with glomerular disease affecting the mesangium. This review aims to give a better understanding of the MCs in health and disease and their role in glomerular crosstalk and inflammation.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"239 2","pages":""},"PeriodicalIF":6.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10492460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global proteomics reveals insulin abundance as a marker of human islet homeostasis alterations","authors":"Andreas F. Mathisen,&nbsp;Shadab Abadpour,&nbsp;Thomas Aga Legøy,&nbsp;Joao A. Paulo,&nbsp;Luiza Ghila,&nbsp;Hanne Scholz,&nbsp;Simona Chera","doi":"10.1111/apha.14037","DOIUrl":"10.1111/apha.14037","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The variation in quality between the human islet samples represents a major problem for research, especially when used as control material. The assays assessing the quality of human islets used in research are non-standardized and limited, with many important parameters not being consistently assessed. High-throughput studies aimed at characterizing the diversity and segregation markers among apparently functionally healthy islet preps are thus a requirement. Here, we designed a pilot study to comprehensively identify the diversity of global proteome signatures and the deviation from normal homeostasis in randomly selected human-isolated islet samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>By using Tandem Mass Tag 16-plex proteomics, we focused on the recurrently observed disparity in the detected insulin abundance between the samples, used it as a segregating parameter, and analyzed the correlated changes in the proteome signature and homeostasis by pathway analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this pilot study, we showed that insulin protein abundance is a predictor of human islet homeostasis and quality. This parameter is independent of other quality predictors within their acceptable range, thus being able to further stratify islets samples of apparent good quality. Human islets with low amounts of insulin displayed changes in their metabolic and signaling profile, especially in regard to energy homeostasis and cell identity maintenance. We further showed that xenotransplantation into diabetic hosts is not expected to improve the pre-transplantation signature, as it has a negative effect on energy balance, antioxidant activity, and islet cell identity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Insulin protein abundance predicts significant changes in human islet homeostasis among random samples of apparently good quality.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"239 2","pages":""},"PeriodicalIF":6.3,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10423139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detecting and exploiting the circadian clock in rheumatoid arthritis","authors":"Siska Wilantri,&nbsp;Hanna Grasshoff,&nbsp;Tanja Lange,&nbsp;Timo Gaber,&nbsp;Luciana Besedovsky,&nbsp;Frank Buttgereit","doi":"10.1111/apha.14028","DOIUrl":"10.1111/apha.14028","url":null,"abstract":"<p>Over the past four decades, research on 24-h rhythms has yielded numerous remarkable findings, revealing their genetic, molecular, and physiological significance for immunity and various diseases. Thus, circadian rhythms are of fundamental importance to mammals, as their disruption and misalignment have been associated with many diseases and the abnormal functioning of many physiological processes. In this article, we provide a brief overview of the molecular regulation of 24-h rhythms, their importance for immunity, the deleterious effects of misalignment, the link between such pathological rhythms and rheumatoid arthritis (RA), and the potential exploitation of chronobiological rhythms for the chronotherapy of inflammatory autoimmune diseases, using RA as an example.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"239 2","pages":""},"PeriodicalIF":6.3,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10054254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroglia: Function and Pathology by Alexei Verkhratsky and Arthur M. Butt","authors":"Tibor Harkany,&nbsp;Tomas Hökfelt","doi":"10.1111/apha.14033","DOIUrl":"10.1111/apha.14033","url":null,"abstract":"&lt;p&gt;“Glial cells are in the brain to support neurons” is one of the commonplaces taught at regular lectures by neuroscientists to future generations of neurobiologists. Never mind that detailed insights into glial physiology and pathobiology are usually neglected in thematic neuroscience curricula. Indeed, the classic bias in the field of neuroscience comes from the term “neuro” itself. General thinking dictates that when one can manipulate specific subtypes of neurons distinguished by a signature of probably a handful of molecules at millisecond precision chemically or by light, and receive a behavioral response from the experimental organism, be this invertebrate or vertebrate, then neurons alone shall be sufficient to organize the brain's output. We could not be more wrong and on an arduous journey to fundamentally misinterpret brain operations if holding onto these views. It is time to acknowledge the contribution of other cell types, cumulatively termed “neuroglia,” with astroglia, oligodendroglia, and microglia being present in the central nervous system alone. Adding Schwann cells, satellite glia, enteric glia, and glial cells of sensory organs to this list is a thrilling reminder that an amazing variety of glial cell types not only exists at around 1:1 ratio but works in unison in the human nervous systems to allow it to reach its computational, intellectual, and emotional power that makes us unique.&lt;/p&gt;&lt;p&gt;“Would you know a renown ‘glioscientist’ as if a neuroscientist?” For many, this could be an unexpectedly challenging question still. Here, we introduce &lt;b&gt;Alexei Verkhratsky&lt;/b&gt; and &lt;b&gt;Arthur M. Butt&lt;/b&gt; as two of the most eminent glia biologists of our time whose new book, titled “&lt;b&gt;Neuroglia: Function and Pathology&lt;/b&gt;” is a wonderfully illustrated, comprehensive, thematic, and insightful account of the vast knowledge that has accumulated on glial cells of both the central and peripheral nervous systems over the past ~150 years. This book, the newest in a series of compendia on glial cells,&lt;span&gt;&lt;sup&gt;1-4&lt;/sup&gt;&lt;/span&gt; is educational for it systematically summarizing the origins, development, anatomy, molecular make-up, membrane biophysics, cellular interactions, and functions in relation to nerve cells and the broader brain homeostasis of each major glial cell type. Yet, it is an enticing read that also answers many unexpected questions ranging from the history of neuroscience (e.g., “do you know who coined the word astrocyte?”) to debunking some of the most pressing dogmas, like the number of neurons versus other cells in the brain. To this point, and using even evolutionary biology, a ~ 1:1 neuron: astrocyte ratio is formulated, which could work well if one considers that each neuron could have its “personal” caretaker, which supports, interacts, facilitates, removes waste, and even protects against disease and demise.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Neuroglia: Function and Pathology&lt;/b&gt; starts with a historical account of discoveries that shaped this fie","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"239 2","pages":""},"PeriodicalIF":6.3,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10037236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal myosin post-translational modifications and ATP turnover time associated with human congenital myopathy-related RYR1 mutations","authors":"Alexander Sonne,&nbsp;Anna Katarina Antonovic,&nbsp;Elise Melhedegaard,&nbsp;Fariha Akter,&nbsp;Jesper L. Andersen,&nbsp;Heinz Jungbluth,&nbsp;Nanna Witting,&nbsp;John Vissing,&nbsp;Edmar Zanoteli,&nbsp;Arianna Fornili,&nbsp;Julien Ochala","doi":"10.1111/apha.14035","DOIUrl":"10.1111/apha.14035","url":null,"abstract":"Conditions related to mutations in the gene encoding the skeletal muscle ryanodine receptor 1 (RYR1) are genetic muscle disorders and include congenital myopathies with permanent weakness, as well as episodic phenotypes such as rhabdomyolysis/myalgia. Although RYR1 dysfunction is the primary mechanism in RYR1‐related disorders, other downstream pathogenic events are less well understood and may include a secondary remodeling of major contractile proteins. Hence, in the present study, we aimed to investigate whether congenital myopathy‐related RYR1 mutations alter the regulation of the most abundant contractile protein, myosin.","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"239 2","pages":""},"PeriodicalIF":6.3,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10029543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased R-spondin 3 contributes to aerobic exercise-induced protection against renal vascular endothelial hyperpermeability and acute kidney injury","authors":"Qing-Feng Xu,&nbsp;Hui Zhang,&nbsp;Ying Zhao,&nbsp;Di Liu,&nbsp;Juan Wei,&nbsp;Lai Jiang,&nbsp;Yu-Jian Liu,&nbsp;Xiao-Yan Zhu","doi":"10.1111/apha.14036","DOIUrl":"10.1111/apha.14036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Exercise training exerts protective effects against sepsis-associated multiple organ dysfunction. This study aimed to investigate whether aerobic exercise protected against sepsis-associated acute kidney injury (AKI) via modulating R-spondin 3 (RSPO3) expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To investigate the effects of aerobic exercise on lipopolysaccharide (LPS)-induced AKI, LPS (20 mg/kg) was intraperitoneally injected after six weeks of treadmill training. To investigate the role of RSPO3 in LPS-induced AKI, wild-type (WT) or inducible endothelial cell-specific RSPO3 knockout (RSPO3^EC−/−) mice were intraperitoneally injected with 12 mg/kg LPS. RSPO3 was intraperitoneally injected 30 min before LPS treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Aerobic exercise-trained mice were more resistant to LPS-induced body weight loss and hypothermia and had a significant higher survival rate than sedentary mice exposed to LPS. Exercise training restored the LPS-induced decreases in serum and renal RSPO3 levels. Exercise or RSPO3 attenuated, whereas inducible endothelial cell-specific RSPO3 knockout exacerbated LPS-induced renal glycocalyx loss, endothelial hyperpermeability, inflammation, and AKI. Bioinformatics analysis results revealed significant increases in the expression of matrix metalloproteinases (MMPs) in kidney tissues of mice exposed to sepsis or endotoxaemia, which was validated in renal tissue from LPS-exposed mice and LPS-treated human microvascular endothelial cells (HMVECs). Both RSPO3 and MMPs inhibitor restored LPS-induced downregulation of tight junction protein, adherens junction protein, and glycocalyx components, thus ameliorating LPS-induced endothelial leakage. Exercise or RSPO3 reversed LPS-induced upregulation of MMPs in renal tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Increased renal expression of RSPO3 contributes to aerobic exercise-induced protection against LPS-induced renal endothelial hyperpermeability and AKI by suppressing MMPs-mediated disruption of glycocalyx and tight and adherens junctions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"239 4","pages":""},"PeriodicalIF":6.3,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10041405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nfix: a transcription factor with an important functional role in cardiac automaticity","authors":"Pietro Mesirca","doi":"10.1111/apha.14034","DOIUrl":"10.1111/apha.14034","url":null,"abstract":"&lt;p&gt;Cardiac automaticity is a fascinating physiological phenomenon, a remarkable challenge driving physiologists and researchers along the centuries.&lt;/p&gt;&lt;p&gt;Already Galen of Pergamon, one of the greatest physicians of antiquity who lived in the 2&lt;sup&gt;nd&lt;/sup&gt; century, starting from his observations that an excised, denervated heart continued spontaneous beating after removal from animal's body, stated that the vital spirit was based on the heart (&lt;i&gt;De usu partium corporis humani&lt;/i&gt;). Nowadays, there is a consensus that the spontaneous cardiac activity, in healthy condition, is generated by a specialized population of cardiomyocytes referred to as pacemaker cells grouped in the sino-atrial node (SAN), a highly heterogeneous thin tissue structure located in the right atrium.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; However, the mechanism underlying pacemaker cells automaticity is still controversial and not totally elucidated. In this issue of ACTA Physiologica, Landi and coworkers&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; describe an unexpected role of Nfix, a transcriptional factor belonging to the Nuclear Factor 1 (NFI) family, in automaticity of pacemaker cardiomyocytes.&lt;/p&gt;&lt;p&gt;The sino-atrial node (SAN) pacemaker cells have a unique action potential profile, characterized by a slow spontaneous depolarizing phase of membrane potential known as “diastolic depolarization”.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Diastolic depolarization slope is a crucial factor in automaticity: the steeper the slope the higher the heart rate and vice versa.&lt;/p&gt;&lt;p&gt;All along the action potential diastolic depolarization phase of SAN pacemaker cells, a net inward ionic current is required to maintain membrane potential depolarization. This ionic current is the resultant of a complex functional interplay among membrane ion channels (mainly HCN4, L- and T-type Ca&lt;sup&gt;++&lt;/sup&gt; channels, and Na&lt;sup&gt;+&lt;/sup&gt; channels) and proteins involved in intracellular calcium dynamic (such as RyR2 receptors, SERCA pump, and type 1 sodium calcium exchanger). The ensemble of these intracellular proteins and plasma membrane ion channels underpins automaticity.&lt;span&gt;&lt;sup&gt;3-5&lt;/sup&gt;&lt;/span&gt;\u0000 &lt;/p&gt;&lt;p&gt;The embryonic origin of SAN pacemaker cells is distinct from that of myocytes of the working heart chambers and those of the His–Purkinje network.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; Recent results have provided new insights into molecular regulators required for pacemaker cell differentiation and function.&lt;/p&gt;&lt;p&gt;These include several transcriptional factors such Tbx3, Nkx2.5, Tbx5, Tbx18, Pitx2, Shox2, Isl1, and BMP4 that have been shown to play a regulatory role in SAN development.&lt;span&gt;&lt;sup&gt;6-10&lt;/sup&gt;&lt;/span&gt;\u0000 &lt;/p&gt;&lt;p&gt;The paper by Landi and collaborators&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; describes, for the first time, the effect of the inhibition of Nfix transcription factor in heart physiology.&lt;/p&gt;&lt;p&gt;In vertebrates, the NFI proteins is encoded by four closely related genes, named Nfia, Nfib, Nfic, and Nfix.&lt;span&gt;&lt;sup&gt;11, 12&lt;/sup&gt;&lt;/span&gt; Th","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"239 2","pages":""},"PeriodicalIF":6.3,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10029019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Slc34a2 expression and paracellular phosphate permeability contribute to high intestinal phosphate absorption in young mice","authors":"Tate MacDonald,&nbsp;Megan R. Beggs,&nbsp;Debbie O'Neill,&nbsp;Kenji Kozuka,&nbsp;Henrik Dimke,&nbsp;R. Todd Alexander","doi":"10.1111/apha.14029","DOIUrl":"10.1111/apha.14029","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Phosphorus is a critical constituent of bone as a component of hydroxyapatite. Bone mineral content accrues rapidly early in life necessitating a positive phosphorus balance, which could be established by a combination of increased renal reabsorption and intestinal absorption. Intestinal absorption can occur via a transcellular pathway mediated by the apical sodium-phosphate cotransporter, <i>Slc34a2</i>/NaPiIIb or via the paracellular pathway. We sought to determine how young mammals increase dietary phosphorus absorption from the small intestine to establish a positive phosphorus balance, a prerequisite for rapid bone growth.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The developmental expression profile of genes mediating phosphate absorption from the small intestine was determined in mice by qPCR and immunohistochemistry. Additionally, Ussing chamber studies were performed on small bowel of young (p7–p14) and older (8- to 17-week-old) mice to examine developmental changes in paracellular Pi permeability and transcellular Pi transport.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Blood and urinary Pi levels were higher in young mice. Intestinal paracellular phosphate permeability of young mice was significantly increased relative to older mice across all intestinal segments. NaPiIIb expression was markedly increased in juvenile mice, in comparison to adult animals. Consistent with this, young mice had increased transcellular phosphate flux across the jejunum and ileum relative to older animals. Moreover, transcellular phosphate transport was attenuated by the NaPiIIb inhibitor NTX1942 in the jejunum and ileum of young mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results are consistent with young mice increasing phosphate absorption via increasing paracellular permeability and the NaPiIIb-mediated transcellular pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"239 2","pages":""},"PeriodicalIF":6.3,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9971889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of cystathionine-gamma lyase dampens vasoconstriction in mouse and human intracerebral arterioles","authors":"Maria Peleli,&nbsp;Kristina S. Lyngso,&nbsp;Frantz Rom Poulsen,&nbsp;Pernille B. L. Hansen,&nbsp;Andreas Papapetropoulos,&nbsp;Jane Stubbe","doi":"10.1111/apha.14021","DOIUrl":"https://doi.org/10.1111/apha.14021","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>In extracerebral vascular beds cystathionine-gamma lyase (CSE) activity plays a vasodilatory role but the role of this hydrogen sulfide (H₂S) producing enzyme in the intracerebral arterioles remain poorly understood. We hypothesized a similar function in the intracerebral arterioles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Intracerebral arterioles were isolated from wild type C57BL/6J mouse (9–12 months old) brains and from human brain biopsies. The function (contractility and secondary dilatation) of the intracerebral arterioles was tested ex vivo by pressure myography using a perfusion set-up. Reverse transcription polymerase chain reaction was used for detecting CSE expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CSE is expressed in human and mouse intracerebral arterioles. CSE inhibition with L-propargylglycine (PAG) significantly dampened the K⁺-induced vasoconstriction in intracerebral arterioles of both species (% of maximum contraction: in human control: 45.4 ± 2.7 versus PAG: 27 ± 5.2 and in mouse control: 50 ± 1.5 versus PAG: 33 ± 5.2) but did not affect the secondary dilatation. This effect of PAG was significantly reversed by the H₂S donor sodium hydrosulfide (NaSH) in human (PAG + NaSH: 38.8 ± 7.2) and mouse (PAG + NaSH: 41.7 ± 3.1) arterioles, respectively. The endothelial NO synthase (eNOS) inhibitor, Nω-Nitro-l-arginine methyl ester (L-NAME), and the inhibitor of soluble guanylate cyclase (sGC), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) reversed the effect of PAG on the K⁺-induced vasoconstriction in the mouse arterioles and attenuated the K⁺-induced secondary dilatation significantly.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CSE contributes to the K⁺-induced vasoconstriction via a mechanism involving H₂S, eNOS, and sGC whereas the secondary dilatation is regulated by eNOS and sGC but not by CSE.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"239 1","pages":""},"PeriodicalIF":6.3,"publicationDate":"2023-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6150198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and risk factors for disability in leprosy patients in Indonesia during the post-elimination era.","authors":"Paula M Samosir, Presstisa Gifta Axelia, Firas F Alkaff, Sovia Salamah, Medhi Denisa Alinda","doi":"10.4081/dr.2023.9777","DOIUrl":"10.4081/dr.2023.9777","url":null,"abstract":"<p><p>Leprosy has been nationally eliminated in Indonesia, but it continues to be a public health problem, with disability contributing to the disease burden. Disability caused by leprosy often results in stigmatization, leading to decreased quality of life. This was a retrospective cross-sectional study using secondary data from primary healthcare centers in one of the districts in the region with the highest number of leprosy patients in Indonesia. All leprosy patients between 2016-2022 were included. Among 189 leprosy patients (mean age 46 years old, 65.6% male), 19% had grade 1 disability and 29.6% had grade 2 disability. Duration of disease, nerve enlargements, leprosy reactions, and symmetric lesions were identified as risk factors for both grade 1 and 2 disability. Being male and having a positive smear test was associated with a higher risk of only grade 2 disability. Disability due to leprosy is still prevalent in the post-elimination era despite the decline in new leprosy cases. Improvement in early case detection and prevention of disability are still needed in the post-elimination era.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"77 1-2","pages":"9777"},"PeriodicalIF":1.1,"publicationDate":"2023-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10848642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41308788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}