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Pi-based mechanism of muscle fatigue during all-out exercise in humans 人类全力运动时肌肉疲劳的pi机制
IF 1.6 4区 医学 Q3 PHYSIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-10-08 DOI: 10.1016/j.resp.2025.104502
Bernard Korzeniewski
The hyperbolic-like decrease with time in power output during all-out exercise (AOE) correlates well with changes in “fatigue-related” metabolites: Pi, H2PO4- (Pi-) and H+. A simple mechanism of muscle fatigue during AOE, named “Pipeak-Pi-distance” mechanism, is proposed and incorporated into a dynamic computer model of the skeletal muscle bioenergetic system. It involves the dependence of the current power output (PO) on the difference between peak Pi (Pipeak), at which exercise is terminated because of fatigue in constant-power exercise (CPE), and current Pi. This mechanism can account for several dynamic properties of the skeletal muscle bioenergetic system during AOE, including PO decrease over time, (almost) identical V̇O2max in AOE and CPE, much faster on-kinetics of V̇O2 and metabolites than PO in AOE, much faster V̇O2 on-kinetics in AOE than CPE, much lower V̇O2 slow component (and higher primary phase II) at the same V̇O2max in AOE than CPE, different rates of approaching a steady-state by PO in different experiments, the V̇O2 decrease during AOE after reaching a maximum observed in some experiments and others. The mechanism is also able to explain mechanistically a broad spectrum of system behaviors, including the above-mentioned phenomena. The Pipeak-Pi-distance mechanism for AOE can be unified with the Pi-double-threshold mechanism proposed previously for CPE (and ramp-incremental exercise, RIE) into the “PiPipeak” mechanism of muscle fatigue. Generally, this unified mechanism, with Pi and Pipeak as central elements, allows to explain the similarities and differences in fatigue generation in various exercise types.
全力运动(AOE)时功率输出随时间呈双曲线状下降与“疲劳相关”代谢物:Pi、H2PO4- (Pi-)和H+的变化密切相关。提出了一种简单的AOE过程中肌肉疲劳的机制,称为“Pipeak-Pi-distance”机制,并将其纳入骨骼肌生物能量系统的动态计算机模型。它涉及到电流输出(PO)对峰值Pi (Pipeak)和电流Pi之间的差的依赖,峰值Pi是恒功率运动(CPE)中由于疲劳而终止的运动。这一机制可以解释AOE期间骨骼肌生物能量系统的几个动态特性,包括PO随时间的减少,AOE和CPE(几乎)相同的V O2max, AOE中V O2和代谢产物的动力学比PO快,AOE中V O2的动力学比CPE快,AOE中相同V O2max的V O2慢组分比CPE低得多(初级II相更高),不同实验中PO接近稳态的速率不同。在AOE过程中,V (O2)在达到某些实验和其他实验观察到的最大值后下降。该机制还能够从机械上解释广泛的系统行为,包括上述现象。AOE的PiPipeak - pi -distance机制可以与之前提出的CPE的pi -双阈值机制(以及坡道增量运动,RIE)统一为肌肉疲劳的“PiPipeak”机制。一般来说,这种以Pi和Pipeak为中心元素的统一机制可以解释各种运动类型中疲劳产生的异同。
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引用次数: 0
Tobacco smoking: A stimulus for blood volume expansion 吸烟:刺激血容量扩张。
IF 1.6 4区 医学 Q3 PHYSIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-10-13 DOI: 10.1016/j.resp.2025.104505
Alexandros Sotiridis , Charalambos Dardamanis-Aidonas , Anastasios Makris , Ioannis Loukas , Nickos Geladas , Maria Koskolou
Tobacco smoking involves the inhalation of carbon monoxide (CO), a gas that binds to hemoglobin molecules to form carboxyhemoglobin (COHb), and thus acutely reduces arterial oxygen content. Whether regular tobacco smoking elicits a compensatory increase in hemoglobin mass (HbM) and concomitant gains in intravascular volumes of even relatively trained individuals was examined in the present study. Thirty young males were split in independent groups based on smoking status (CS; chronic smokers and NS; non-smokers) and aerobic fitness level (MF; more fit and LF; less fit) (CS-MF, CS-LF, NS-MF and NS-LF; n = 8 for all but the first group). CS had been smoking > 10 cigarettes·day−1 at least for the last three years. Assessed using an incremental running exercise test to exhaustion, the age-adjusted VO2peak was selected as the criterion for the inclusion in the MF and LF groups, respectively. The CO-rebreathing technique was applied to assess HbM and intravascular blood volumes. A two-way ANOVA was performed to detect differences in means of hematological and endurance performance parameters. VO2peak was found higher in MF groups (p < 0.001) but was similar between groups of similar fitness level (p = 0.57). Accordingly, peak aerobic speed was lower in CS (p < 0.001) and LF groups (p = 0.004). HbM (p = 0.013), total blood (p = 0.001) and red cell (p < 0.001) volumes were higher in CS groups. Despite the underlying expansion in HbM and total blood volume in smokers of varying fitness levels, endurance performance seems to be impaired. Future research could develop insight into the regulation of hematocrit in smokers.
吸烟涉及吸入一氧化碳(CO),这种气体与血红蛋白分子结合形成碳氧血红蛋白(COHb),从而急剧降低动脉氧含量。在本研究中,研究人员检验了定期吸烟是否会引起血红蛋白质量(HbM)的代偿性增加,并伴随训练有素的个体的血管内体积增加。30名年轻男性根据吸烟状况(CS;慢性吸烟者和NS;不吸烟者)和有氧健身水平(MF;更健康和LF;不健康)(CS-MF, CS-LF, NS-MF和NS-LF;除第一组外,其余组n=8)分为独立组。至少在过去的三年里,CS每天抽100支烟。使用增量跑步运动测试评估疲劳,选择年龄调整后的vo2峰值分别作为MF组和LF组的纳入标准。采用co -再呼吸技术评估HbM和血管内血容量。采用双向方差分析来检测血液学和耐力表现参数的差异。MF组vo2峰值升高(p
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引用次数: 0
CT-scan assessment of lung volumes and effect of gravity on lung ventilation during and after total liquid ventilation in piglets ct扫描评估仔猪全液体通气期间和之后肺容量及重力对肺通气的影响。
IF 1.6 4区 医学 Q3 PHYSIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-10-13 DOI: 10.1016/j.resp.2025.104507
Christophe Morin , Alexandru Panaitescu , Gabriel Richard , Sarah-Gabrielle Taillandier-Pensarini , Nathalie Samson , Clément Bouchard , Stéphanie Laferté , Émile Vallières , Matthias Kohlhauer , Renaud Tissier , Etienne Croteau , Roger Lecomte , Jean-Paul Praud , Philippe Micheau , Etienne Fortin-Pellerin
Total liquid ventilation (TLV) offers hope for helping nano-preterm infants adapt to the extrauterine environment at birth. We aimed to test whether lung volumes could be maintained over time during TLV and whether the prone position altered the distribution of perflubron during and following TLV. CT scan images were acquired in seven newborn piglets during 180 min of TLV, followed by 120 min of weaning. End-expiratory lung volumes increased from 43.0 [38.1, 44.4] cm3/kg at baseline to 53.5 [50.6, 67.8] cm3/kg (p = 0.036) at 60 min of TLV through recruitment of the dependent (posterior) lung regions. They remained stable thereafter at 55.4 [45.0, 64.5] cm3/kg at 150 min (p = 0.5 vs. 60 min). Change to the prone position during TLV did not alter the proportion of the tidal volume distributed to the anterior lung regions (p = 0.9). However, the prone position during weaning (rotating experimental group, n = 3) favored distribution of the gaseous tidal volume to the nondependent lung regions. In conclusion, perflubron did not accumulate in the lungs after the initial recruitment of gravity-dependent regions. In addition, prone positioning did not affect tidal volume distribution during TLV but increased ventilation of the nondependent lung regions during weaning.
全液体通气(TLV)为纳米早产儿在出生时适应子宫外环境提供了希望。我们的目的是测试TLV期间肺容量能否随时间保持,以及俯卧位是否会改变TLV期间和之后全氟隆的分布。7头新生仔猪在TLV 180min和断奶120min期间获得CT扫描图像。呼气末肺容量从基线时的43.0 [38.1,44.4]cm3/kg增加到TLV 60min时的53.5 [50.6,67.8]cm3/kg (p = 0.036)。此后在150min时保持稳定在55.4 [45.0,64.5]cm3/kg (p = 0.5 vs. 60min)。TLV时俯卧位的改变并没有改变潮气量在肺前区分布的比例(p = 0.9)。然而,断奶时俯卧位(旋转实验组,n=3)有利于气态潮气量向非依赖性肺区域的分布。综上所述,在最初的重力依赖区招募后,全氟隆不会在肺部积聚。此外,俯卧位不影响TLV期间的潮气量分布,但增加了脱机期间非依赖性肺区域的通气。
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引用次数: 0
Dysanapsis is a determinant of expiratory flow limitation during exercise in master athletes 运动健将在运动过程中,呼气功能障碍是呼气流量限制的决定因素。
IF 1.6 4区 医学 Q3 PHYSIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-10-04 DOI: 10.1016/j.resp.2025.104500
Valentin Mons , Toni Haddad , Colin Lavigne , Olivier Meste , Benjamin Mauroy , Grégory M. Blain

Introduction

Previous research has identified expiratory flow limitation (EFL) as a limiting factor to exercise performance in older endurance athletes (i.e. master athletes), who represent a model of successful aging. A mismatch between airway size and lung size, termed dysanapsis, has been proposed as a contributor to EFL during exercise. We thus investigated whether dysanapsis determine the prevalence and severity of EFL in master athletes during exercise.

Methods

Four female and fourteen male master athletes (age, 67 ± 5 years; V̇O2max, 50.9 ± 5.7 mL.min−1.kg−1) performed an incremental exercise test to exhaustion on a cycle ergometer. The maximal expiratory flow volume (MEFV) curve was assessed at rest and operational lung volumes were determined with participants performing inspiratory capacity maneuvers at each exercise workload. EFL severity was estimated as the percentage of the tidal expiratory volume that overlapped the MEFV curve. Dysanapsis was quantified using spirometry-derived indices.

Results

All participants started experiencing EFL at workloads (WEFL) ranging from 40 % to 100 %PPO (WEFL = 68 ± 20 %PPO). EFL severity reached 46 ± 21 % at peak exercise. Lower values across dysanapsis indices, reflecting smaller airway size for a given lung volume, were correlated with lower WEFL (r²>0.490, P < 0.001) and greater EFL severity (r²>0.243, P < 0.038). Individuals experiencing EFL at lower intensities (i.e. lower WEFL) showed greater EFL severity (r²=0.571, P < 0.001).

Conclusion

Our results suggest that dysanapsis is a key determinant of EFL in master athletes, likely contributing to its earlier onset at lower workloads and to its increased severity. These findings have implications for understanding respiratory limitations during exercise in older adults.
先前的研究已经确定呼气流量限制(EFL)是老年耐力运动员(即大师运动员)运动表现的限制因素,他们代表了成功衰老的模型。气道大小和肺大小之间的不匹配,称为肺功能障碍,被认为是运动期间EFL的一个因素。因此,我们研究了功能障碍是否决定了运动期间优秀运动员EFL的患病率和严重程度。方法:女运动员4名,男运动员14名,年龄67±5岁,vo2max 50.9±5.7mL.min-1。Kg-1)在循环测力仪上进行了累进式运动测试。在休息时评估最大呼气流量(MEFV)曲线,并通过参与者在每个运动负荷下进行吸气量操作来确定操作肺容量。以MEFV曲线重叠的呼气量占呼气量的百分比来估计EFL严重程度。使用肺活量测定衍生的指标量化肺功能障碍。结果:所有参与者在工作负荷(WEFL)范围从40%到100%PPO (WEFL = 68±20%PPO)开始经历EFL。运动高峰时EFL严重程度达到46±21%。较低的肺功能障碍指数反映了给定肺容量下较小的气道尺寸,与较低的WEFL (r²bb0.490, P0.243, PEFL)相关,表明EFL严重程度较高(r²=0.571,p)。结论:我们的研究结果表明,功能障碍是优秀运动员EFL的关键决定因素,可能有助于其在较低负荷下更早发病,并增加其严重程度。这些发现对理解老年人运动时的呼吸限制具有启示意义。
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引用次数: 0
Integration of CO2 clearance and continuous neurally adjusted ventilatory assist in an animal model of respiratory distress 在呼吸窘迫动物模型中CO2清除和连续神经调节通气辅助的整合。
IF 1.6 4区 医学 Q3 PHYSIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-09-27 DOI: 10.1016/j.resp.2025.104499
Christer Sinderby , Thiago Bassi , Ling Liu , Daijiro Takahashi , Songqiao Liu , Ewan Goligher , Jennifer Beck

Background

A mode of ventilation is introduced that integrates CO2 clearance (“Through-Flow”, TF) with Continuous Neurally Adjusted Ventiator Assist (cNAVA). The new mode, referred to as “TF+cNAVA”, is a unidirectional flow system where inspiratory lumen(s) within an ET tube delivers fresh gas at the carina and the main ET tube lumen allows overflow of fresh gas to provide assist in proportion to the electrical activity of the diaphragm (Edi). The aim was to evaluate the effect of TF+cNAVA on breathing parameters during respiratory provocations, its reproducibility, and its sustainability. Conventional NAVA was the comparison.

Methods

46 rabbits were studied in three protocols: (i) NAVA vs. TF+cNAVA in open chest with added dead space, acute lung injury (ALI), single lung ventilation, and vagotomy (n = 8); (ii) Eight repeated comparisons, to demonstrate reproducibility (n = 8); (iii) ALI rabbits (n = 30) randomized to either NAVA or TF+cNAVA (6 h). Parameters studied: Edi, tidal volume (VT), breathing frequency (FB), minute ventilation (VE), transpulmonary pressure (PL), and PaCO2.

Results

With added provocations, NAVA showed an increase in Edi, VT, FB, PL and VE from baseline by 43 % (P = 0.004). TF+cNAVA significantly reduced Edi, VT, FB, PL, and VE from baseline, by 73 % (P < 0.001). In NAVA vs. TF+cNAVA crossover, TF+cNAVA consistently reached apneic levels for Edi, VT, FB, PL, and VE. During 6 h of TF+cNAVA, PaCO2, Edi, VT, FB, PL, and VE were significantly reduced compared to NAVA and baseline.

Conclusion

TF+cNAVA unloads respiratory muscles and suppresses respiratory drive, while reducing lung distending pressure.
背景:介绍了一种将CO2清除(“Through-Flow”,TF)与连续神经调节通气辅助(Continuous neural Adjusted Ventiator Assist, cNAVA)相结合的通气模式。这种新模式被称为“TF+cNAVA”,是一种单向流动系统,在这种系统中,ET管内的吸气腔将新鲜气体输送到carina,而主ET管腔允许新鲜气体溢出,以提供与隔膜(Edi)的电活动成比例的辅助。目的是评估TF+cNAVA对呼吸刺激期间呼吸参数的影响,其再现性和可持续性。常规NAVA作为对照。方法:对46只家兔进行3种治疗方案的研究:(i) NAVA与TF+cNAVA在开胸增加死腔、急性肺损伤(ALI)、单肺通气和迷走神经切开术(n = 8);8次重复比较,以证明可重复性(n = 8);(iii) ALI兔(n=30)随机分为NAVA组或TF+cNAVA组(6小时)。研究参数:Edi、潮气量(VT)、呼吸频率(FB)、分气量(VE)、转肺压(PL)、PaCO2。结果:随着挑衅的增加,NAVA显示Edi、VT、FB、PL和VE较基线增加43% (P=0.004)。与基线相比,TF+cNAVA显著降低了Edi、VT、FB、PL和VE,降低了73% (PT、FB、PL和VE)。在TF+cNAVA治疗的6小时内,PaCO2、Edi、VT、FB、PL和VE与NAVA和基线相比显著降低。结论:TF+cNAVA可减轻呼吸肌负荷,抑制呼吸驱动,降低肺扩张压。
{"title":"Integration of CO2 clearance and continuous neurally adjusted ventilatory assist in an animal model of respiratory distress","authors":"Christer Sinderby ,&nbsp;Thiago Bassi ,&nbsp;Ling Liu ,&nbsp;Daijiro Takahashi ,&nbsp;Songqiao Liu ,&nbsp;Ewan Goligher ,&nbsp;Jennifer Beck","doi":"10.1016/j.resp.2025.104499","DOIUrl":"10.1016/j.resp.2025.104499","url":null,"abstract":"<div><h3>Background</h3><div>A mode of ventilation is introduced that integrates CO<sub>2</sub> clearance (“Through-Flow”, TF) with Continuous Neurally Adjusted Ventiator Assist (cNAVA). The new mode, referred to as “TF+cNAVA”, is a unidirectional flow system where inspiratory lumen(s) within an ET tube delivers fresh gas at the carina and the main ET tube lumen allows overflow of fresh gas to provide assist in proportion to the electrical activity of the diaphragm (Edi). The aim was to evaluate the effect of TF+cNAVA on breathing parameters during respiratory provocations, its reproducibility, and its sustainability. Conventional NAVA was the comparison.</div></div><div><h3>Methods</h3><div>46 rabbits were studied in three protocols: (i) NAVA vs. TF+cNAVA in open chest with added dead space, acute lung injury (ALI), single lung ventilation, and vagotomy (n = 8); (ii) Eight repeated comparisons, to demonstrate reproducibility (n = 8); (iii) ALI rabbits (n = 30) randomized to either NAVA or TF+cNAVA (6 h). Parameters studied: Edi, tidal volume (V<sub>T</sub>), breathing frequency (F<sub>B</sub>), minute ventilation (V<sub>E</sub>), transpulmonary pressure (P<sub>L</sub>), and PaCO<sub>2</sub>.</div></div><div><h3>Results</h3><div>With added provocations, NAVA showed an increase in Edi, V<sub>T</sub>, F<sub>B</sub>, P<sub>L</sub> and V<sub>E</sub> from baseline by 43 % (P = 0.004). TF+cNAVA significantly reduced Edi, V<sub>T</sub>, F<sub>B</sub>, P<sub>L</sub>, and V<sub>E</sub> from baseline, by 73 % (P &lt; 0.001). In NAVA vs. TF+cNAVA crossover, TF+cNAVA consistently reached apneic levels for Edi, V<sub>T</sub>, F<sub>B</sub>, P<sub>L</sub>, and V<sub>E</sub>. During 6 h of TF+cNAVA, PaCO<sub>2</sub>, Edi, V<sub>T</sub>, F<sub>B</sub>, P<sub>L</sub>, and V<sub>E</sub> were significantly reduced compared to NAVA and baseline.</div></div><div><h3>Conclusion</h3><div>TF+cNAVA unloads respiratory muscles and suppresses respiratory drive, while reducing lung distending pressure.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"339 ","pages":"Article 104499"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191943","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}
引用次数: 0
Mitochondria targeted hydrogen sulfide donor AP39 attenuates allergic airway inflammation and airway hyperreactivity in mouse 线粒体靶向硫化氢供体AP39减轻小鼠过敏性气道炎症和气道高反应性。
IF 1.6 4区 医学 Q3 PHYSIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-10-06 DOI: 10.1016/j.resp.2025.104501
Bartu Altiparmak , Yasemin Karaman , Olcay Kurtulan , Sevgen Celik Onder , Turgut Emrah Bozkurt

Background

Asthma is a multifactorial chronic inflammatory airway disease affecting 5 % of children and 10 % of adults and there is no curative treatment. Recent studies have revealed that mitochondrial dysfunction is an important contributor to the pathophysiology of various respiratory diseases.

Objectives

In this study, the effect of AP39, a mitochondria-targeted slow-releasing hydrogen sulfide (H2S) donor, was investigated in a mouse model of ovalbumin (OVA)-induced allergic asthma.

Methods

Pulmonary function (airway resistance and dynamic compliance), inflammatory cells and cytokines in bronchoalveolar lavage (BAL) fluid, and histopathology of the lungs were evaluated in 8–12-week-old female C57BL/6 mice.

Results

The OVA-induced allergic asthma model resulted in bronchial hyperreactivity, inflammatory cell infiltration in peribronchial and parenchymal areas in the lungs, increased Th2 cytokines and eosinophil numbers in BAL fluid. Treatment with AP39 (1000 nmol/kg) prevented bronchial hyperreactivity and suppressed the elevated IL-4, IL-5 and IL-13 cytokine levels, inhibited the increase of lymphocyte and eosinophil cells, and reduced histopathological changes in lung tissue. Treatment with a lower dose of AP39 (250 nmol/kg) had slightly less but still significant effects on bronchial hyperreactivity, inflammatory cells and histopathological changes, yet had no effect on cytokine levels.

Conclusion

AP39 treatment prevented pathophysiological changes in allergic airway inflammation. Therefore, targeting the mitochondria with H2S donors may be a promising therapeutic potential in allergic respiratory diseases.
背景:哮喘是一种多因素慢性炎症性气道疾病,影响5%的儿童和10%的成人,并且没有治愈的治疗方法。近年来的研究表明,线粒体功能障碍是多种呼吸系统疾病病理生理的重要因素。目的:研究线粒体靶向缓释硫化氢(H2S)供体AP39对卵清蛋白(OVA)致过敏性哮喘小鼠模型的影响。方法:观察8-12周龄雌性C57BL/6小鼠肺功能(气道阻力和动态顺应性)、支气管肺泡灌洗液(BAL)中炎症细胞和细胞因子的变化及肺组织病理学变化。结果:ova诱导的变应性哮喘模型引起支气管高反应性,支气管周围和肺实质炎症细胞浸润,BAL液Th2细胞因子和嗜酸性粒细胞数量升高。AP39 (1000 nmol/kg)可抑制支气管高反应性,抑制IL-4、IL-5和IL-13细胞因子升高,抑制淋巴细胞和嗜酸性粒细胞增加,减轻肺组织病理改变。低剂量AP39 (250 nmol/kg)对支气管高反应性、炎症细胞和组织病理学改变的影响略小,但仍有显著性作用,而对细胞因子水平无影响。结论:AP39治疗可预防变应性气道炎症的病理生理变化。因此,用H2S供体靶向线粒体可能是治疗过敏性呼吸系统疾病的一种有前景的治疗方法。
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引用次数: 0
Analysis of the structure and surfactant activity of formulations with exogenous pulmonary surfactant as an antibiotic carrier 外源性肺表面活性物质作为抗生素载体的配方结构及活性分析。
IF 1.6 4区 医学 Q3 PHYSIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-10-07 DOI: 10.1016/j.resp.2025.104503
Alejandra Cimato , José Degrossi , Graciela Facorro , María Martínez Sarrasague
Chronic respiratory diseases (CRD) account for approximately 15 % of global deaths annually, with respiratory infections being a significant cause of morbidity, especially in CRD patients. Inhaled antibiotics (ATBs) like Tobramycin and Gentamicin have shown promise in reducing microbial load and improving lung function. However, the conventional delivery methods—typically nebulization of formulations initially designed for systemic use—may result in undesirable side effects. This study explores the potential of utilizing exogenous pulmonary surfactant (EPS) as a carrier for pulmonary drug delivery, aiming to enhance antibiotic efficacy while minimizing systemic toxicity. We developed formulations combining EPS with commonly used ATBs (Amphotericin B, Levofloxacin, Gentamicin, and Itraconazole) and analyzed the macrostructure, bilayer organization, and surfactant activity of EPS. Using, UV and electron spin resonance (ESR) spectroscopies and pulsating bubble surfactometer, we evaluated the structural changes, bilayer fluidity and the surface properties. The results indicate that EPS can effectively integrate hydrophobic antibiotics, retain surfactant properties, while preserve its surface-active capabilities. Notably, Gentamicin significantly increased the proportion of the heavy surfactant fraction and modified the fluidity and lateral structure of the surfactant. The presence of Levofloxacin in EPS membranes slightly increased the bilayer rigidity without compromising surfactant functionality. These findings highlight the potential of EPS as a versatile carrier for targeted pulmonary antibiotic delivery, presenting a framework for the development of more effective treatments for pulmonary infections. Further exploration of the interaction between antibiotics and surfactant components is warranted to optimize formulation strategies in clinical applications.
慢性呼吸道疾病(CRD)每年约占全球死亡人数的15%,呼吸道感染是发病的一个重要原因,特别是在CRD患者中。吸入抗生素(ATBs),如妥布霉素和庆大霉素,已显示出减少微生物负荷和改善肺功能的希望。然而,传统的给药方法——通常是最初设计用于全身使用的配方雾化——可能会导致不良的副作用。本研究探讨了利用外源性肺表面活性物质(EPS)作为肺给药载体的潜力,旨在提高抗生素的疗效,同时最大限度地减少全身毒性。我们研制了EPS与常用ATBs(两性霉素B、左氧氟沙星、庆大霉素、伊曲康唑)联合的配方,并分析了EPS的宏观结构、双层组织和表面活性剂活性。利用紫外光谱、电子自旋共振(ESR)光谱和脉动气泡表面计,对其结构变化、双层流动性和表面性能进行了评价。结果表明,EPS能有效整合疏水抗生素,在保留表面活性剂性能的同时,保持其表面活性。庆大霉素显著提高了重表面活性剂组分的比例,改变了表面活性剂的流动性和横向结构。左氧氟沙星在EPS膜中的存在略微增加了双层刚性,而不影响表面活性剂的功能。这些发现突出了EPS作为靶向肺部抗生素递送的多功能载体的潜力,为开发更有效的肺部感染治疗提供了框架。进一步探索抗生素与表面活性剂组分之间的相互作用,优化临床应用中的处方策略是有必要的。
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引用次数: 0
Nasal cycling effects in intranasal drug delivery efficiency to the olfactory cleft 鼻循环对鼻内给药效率的影响。
IF 1.6 4区 医学 Q3 PHYSIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-10-13 DOI: 10.1016/j.resp.2025.104506
Michelle H. Kim , Dennis O. Frank-Ito

Background

Optimizing olfactory cleft drug delivery remains a significant challenge due to the anatomical complexity of the nasal cavity and olfactory cleft location. While various strategies have been explored to improve targeting, the influence of nasal cycling remains poorly understood. This study investigates the impact of nasal cycling on olfactory-targeted drug delivery.

Methods

Three-dimensional nasal airway models were reconstructed from radiographic images of 32 healthy adults and classified into Mid (n = 16), Mild (n = 8), and Extreme (n = 8) nasal cycling. Computational simulations were conducted at 15 L/min inspiratory flowrate. Drug particle transport was simulated under varied conditions, including spray velocities (1, 5, 10 m/s), plume angles (10°, 20°, 40°, 70°), and release locations (10 mm Center, 20 mm Center, 20 mm Mid-Superior, and 20 mm Max-Superior) with head held upright. 175,000 drug particles (1–50μm) were released per nostril.

Results

Across all classifications, olfactory deposition was greater on less patent (LP) side (median: Mid=4.89 %, Mild=1.82 %, Extreme=5.32 %) than more patent (MP) side (median: Mid=1.31 %, Mild=0.25 %, Extreme=0.23 %). Pairwise comparisons revealed no statistically significant differences in deposition between cycling classifications for either LP or MP (all p > 0.05), with effect sizes indicating small differences (rank-biserial correlation range: LP=–0.19–0.06; MP=0.02–0.26). Narrow plume angles (10°) consistently enhanced LP deposition, wider angles (70°) were more effective on MP. Spray release location varied according to cycling classification, and 1 m/s spray velocity yielded the highest frequency of olfactory deposition across all cycling states.

Conclusion

These preliminary results demonstrate that nasal cycling exerts a dynamic influence on intranasal drug deposition patterns within the olfactory cleft.
背景:由于鼻腔解剖的复杂性和嗅裂的位置,优化嗅裂给药仍然是一个重大的挑战。虽然已经探索了各种策略来提高靶向性,但鼻腔循环的影响仍然知之甚少。本研究探讨鼻腔循环对嗅觉靶向给药的影响。方法:利用32例健康成人的x线影像重建三维鼻气道模型,将其分为中度(n=16)、轻度(n=8)和重度(n=8)鼻循环。在15L/min吸气流量下进行了计算模拟。模拟了不同条件下的药物颗粒运输,包括喷雾速度(1、5、10m/s)、羽流角度(10°、20°、40°、70°)和释放位置(10mm Center、20mm Center、20mm Mid-Superior和20mm Max-Superior),头部保持直立。每鼻孔释放17.5万个1 ~ 50μm的药物颗粒。结果:在所有分类中,较少专利侧(LP)的嗅觉沉积(中位数:Mid=4.89%, Mild=1.82%, Extreme=5.32%)大于较多专利侧(MP)(中位数:Mid=1.31%, Mild=0.25%, Extreme=0.23%)。两两比较显示,无论是LP还是MP的循环分类之间的沉积差异均无统计学意义(p均为0.05),效应量表明差异很小(秩双相关范围:LP=-0.19-0.06; MP=0.02-0.26)。窄羽角(10°)持续增强LP沉积,宽羽角(70°)对MP更有效。喷淋释放位置随循环类型的不同而不同,在所有循环状态下,1m/s的喷淋速度产生的嗅觉沉积频率最高。结论:这些初步结果表明鼻循环对鼻内药物在嗅裂内的沉积模式有动态影响。
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引用次数: 0
Modality of tracheal sensory inputs modulate swallowing reflexibility and discharge patterns of neurons of the dorsal swallowing group in rats 气管感觉输入方式调节大鼠背侧吞咽组神经元的吞咽反射和放电模式
IF 1.6 4区 医学 Q3 PHYSIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-10-30 DOI: 10.1016/j.resp.2025.104510
Eriko Shimazaki , Tomoya Ishida , Yuki Sato , Hiroyuki Shuto , Akimichi Minesaki , Rishi R. Dhingra , Mathias Dutschmann , Yoichiro Sugiyama

Objective

Desensitization of the larynx significantly impairs swallowing function in patients with tracheostomies. Although it is clinically relevant that adequate airway clearance helps to improve swallowing responsiveness, a robust theoretical proposal has not been provided. Hence, we investigated the impact of prolonged fluid irritation of the trachea and larynx on the swallowing reflex. We additionally analyzed discharge activities of the swallowing-related neurons in presence and absence of airway fluid accumulation.

Methods

We analyzed the likelihood of swallowing evoked by electrical stimulation of the superior laryngeal nerve or oral water injection before and after removal of fluid accumulation in the trachea and larynx using air flow in perfused rats (n = 15). We then transected the superior laryngeal and vagus nerves which convey critical laryngotracheal sensory information. We recorded changes in the neuronal activities in the presence or absence of airway fluid contamination using multi-electrode arrays (n = 8).

Results

The frequency of swallows was increased by the removal of airway fluid accumulation and this change lasted at least 60 min. The effects were abolished following the section of either the superior laryngeal or vagus nerve. Specifically, we found that centrally recorded swallowing neurons showed changes in spontaneous discharge activities in the presence or absence of fluid-related laryngotracheal sensory stimulation.

Conclusion

A diminished likelihood of swallowing caused by prolonged airway irritation can be cautiously improved through airway clearance with respiratory airflow via central and peripheral neuromodulation. Our findings provide a fundamental mechanism to recover impaired laryngotracheal susceptibility for severe dysphagia such as post-tracheostomy dysphagia.
目的探讨气管切开术患者咽喉脱敏对吞咽功能的影响。虽然充分的气道间隙有助于改善吞咽反应性在临床上是相关的,但还没有一个强有力的理论建议。因此,我们研究了气管和喉部长期液体刺激对吞咽反射的影响。我们还分析了存在和不存在气道积液时吞咽相关神经元的放电活动。方法分析灌注大鼠气管及喉部积液清除前后电刺激喉上神经或口服水引起吞咽的可能性(n = 15)。然后我们横切喉上神经和迷走神经,它们传递关键的喉-气管感觉信息。我们使用多电极阵列记录了存在或不存在气道液体污染时神经元活动的变化(n = 8)。结果随着气道积液的清除,吞咽次数增加,这种变化持续至少60 min。在切除喉上神经或迷走神经后,这种效果消失。具体来说,我们发现中央记录的吞咽神经元在存在或不存在与液体相关的喉气管感觉刺激时表现出自发放电活动的变化。结论通过调节中枢神经和周围神经的呼吸气流清除气道,可减少气道刺激引起的吞咽可能性。我们的研究结果为恢复严重吞咽困难(如气管切开术后吞咽困难)的受损喉气管易感性提供了一种基本机制。
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引用次数: 0
Peak V̇O2, not resting spleen volume predicts cellular immune marker mobilization after aerobic exercise 在有氧运动后,预测细胞免疫标志物动员的是峰值V氧,而不是静息脾脏体积。
IF 1.6 4区 医学 Q3 PHYSIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-10-15 DOI: 10.1016/j.resp.2025.104508
Damir Zubac , Ante Obad , Daniela Šupe-Domić , Mirela Radman-Livaja , Nikolina Mužinić-Režić , Ana Bošnjak , Vladimir Ivančev , Zoran Valić

Background

This study aimed to examine white blood cell and platelet mobilization after moderate-intensity aerobic exercise, its association with spleen volume, and the potential mediating role of peak V̇O₂.

Methods

Twenty participants (24 ± 4 years-old) completed all study procedures, including a detailed medical examination, supine cardio-pulmonary exercise test (CPET) and three step-transitions from 20 W to a moderate-intensity power output, equivalent to V̇O2 uptake at 90 % gas exchange threshold. During these step-transitions cardiometabolic and splenic responses were simultaneously measured. Blood samples were collected before and immediately after moderate-intensity cycling.

Results

In response to aerobic exercise, the spleen volume was significantly reduced (by 83 ± 39 mL, p = 0.001), while the increase in systemic immune inflammation index (SII), neutrophil-lymphocyte-ratio (NLR) and serum TNF-α protein concentration were not significant. A significant decrease of −7 % (p = 0.049, ⅾ=0.48) was observed for platelet-lymphocyte-ratio (PLR). A multiple regression analysis revealed that a higher peak V̇O₂ (p = 0.031), but not resting spleen volume (p = 0.614), predicted the post-exercise increase in PLR (p = 0.049), explaining 25 % of the common variance. Changes in NLR (p = 0.423), SII (p = 0.198) or TNF-α (p = 0.808) were not associated with peak V̇O₂ or resting spleen volume.

Conclusion

Apparently, greater cardiorespiratory fitness, rather than resting spleen volume, modulates specific and transient changes of some circulating immune markers following moderate-intensity cycling.
背景:本研究旨在探讨中等强度有氧运动后白细胞和血小板的动员及其与脾体积的关系,以及峰值V O₂的潜在介导作用。方法:20名参与者(24±4岁)完成了所有的研究程序,包括详细的体格检查、仰卧位心肺运动试验(CPET)和从20W到中等强度功率输出的三个阶梯转换,相当于90%气体交换阈值下的V²O2摄取。在这些阶梯转换过程中,同时测量心脏代谢和脾反应。在中等强度骑行之前和之后立即采集血液样本。结果:有氧运动后,大鼠脾脏体积明显减小(83±39mL, p=0.001),而全身免疫炎症指数(SII)、中性粒细胞-淋巴细胞比(NLR)和血清TNF-α蛋白浓度升高不显著。血小板淋巴细胞比(PLR)显著降低-7% (p=0.049, =0.48)。多元回归分析显示,较高的峰值V O₂(p=0.031)而不是静息脾脏体积(p=0.614)预测运动后PLR的增加(p=0.049),解释了25%的共同方差。NLR (p=0.423)、SII (p=0.198)或TNF-α (p=0.808)的变化与峰值V O₂或静息脾体积无关。结论:显然,中等强度循环后,更大的心肺适能,而不是静息脾体积,调节了一些循环免疫标志物的特异性和短暂性变化。
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引用次数: 0
期刊
Respiratory Physiology & Neurobiology
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