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1.
James Arthos Claudia Cicala Fatima Nawaz Siddappa N. Byrareddy Francois Villinger Philip J. Santangelo Aftab A. Ansari Anthony S. Fauci 《Current HIV/AIDS reports》2018,15(2):127-135
Purpose of Review
Acute HIV infection is characterized by high-level viral replication throughout the body’s lymphoid system, particularly in gut-associated lymphoid tissues resulting in damage to structural components of gut tissue. This damage is irreversible and believed to contribute to the development of immune deficiencies. Antiretroviral therapy (ART) does not restore gut structure and function. Studies in macaques point to an alternative treatment strategy that may ameliorate gut damage. Integrin α4β7 mediates the homing of lymphocytes to gut tissues. Vedolizumab, a monoclonal antibody (mAb) antagonist of α4β7, has demonstrated efficacy and has been approved for the treatment of inflammatory bowel disease in humans. Here, we describe our current knowledge, and the gaps in our understanding, of the role of α4β7 in HIV pathogenesis and treatment.Recent Findings
When administered to macaques prior to infection, a nonhuman primate analogue of vedolizumab prevents transmission of SIV. In combination with ART, this mAb facilitates durable virologic control following treatment interruption.Summary
Targeting α4β7 represents a novel therapeutic approach to prevent and treat HIV infection.2.
Objective and Design: To investigate the effects of 2-adrenoceptor (2-AR) stimulation on endotoxin-induced liver damage and systemic cytokine levels in rats.Subjects: Standard male Wistar rats.Treatment: A disease-model of lipolysaccharide (LPS)-induced acute systemic inflammation was used. The 2-selective AR agonist clenbuterol was administered before, during, and after LPS-challenge to investigate its effects on the acute inflammatory response and associated liver-failure.Methods: The following parameters have been measured in plasma: TNF, IL-1, IL-6, IL-10, AST, ALT, and Bilirubin. Liver histological examination was performed to look for changes in tissue morphology.Results: Administration of clenbuterol (p.o.) one hour before, or intravenous at the same time as LPS-challenge resulted in a marked reduction of plasma levels of TNF, IL-1, and IL-6. A change both in plasma-level and in time-concentration profile of the anti-inflammatory cytokine IL-10 was found. Clenbuterol minimized LPS-induced liver damage, as represented by significantly lowered concentrations of several parameters for liver-failure (AST, ALT, Bilirubin), and improved hepatic tissue morphology. Clenbuterol administration after LPS challenge failed to inhibit TNF-release but reduced liver-damage. Simultaneous use of the 2-AR antagonist propranolol augmented LPS-induced liver failure, suggesting a role of endogenous adrenoceptor-agonists in prevention of organ-failure during systemic inflammation.Conclusions: The results indicate that a selective 2-AR agonist might be used as an additional therapeutic agent in the clinic for the treatment of (acute) systemic inflammatory disorders in order to reduce or prevent subsequent liver failure.Received 3 March 2003; returned for revision 4 April 2003; returned for final revision 3 October 2003; accepted by M.Parnham 29 October 2003 相似文献
3.
Activation of μ-opioid receptors (μ-OR) by the highly selective agonist DAGO (100 μg/kg) significantly increased the immune
response in CBA mice. This effect of the μ agonist was prevented by prior blockade of dopamine D2 receptors with haloperidol (2 mg/kg). In contrast, the selective D1 receptor antagonist SCH 23390 (1 mg/kg) had no effect on the nature of the immune reaction in response to antigen (sheep
erythrocytes, 5·108 cells). However, blockade of both types of dopamine receptor led to the same effect-immunosuppression. These data lead to
the suggestion that D1 and D2 receptors make different contributions to modulating immunogenesis on activation of μ-OR.
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Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 92, No. 5, pp. 546–551, May, 2006. 相似文献
4.
T. A. Zapara A. L. Proskura A. S. Ratushnyak M. B. Shtark O. I. Epstein 《Bulletin of experimental biology and medicine》2009,147(1):42-44
The capacity of living systems to perceive low-intensity stimuli sometimes inducing protective reactions is still little studied.
Incubation of neurons under conditions increasing the content of cAMP and Ca2+ increases the amplitude of their responses to lidocaine (10−3 M). After cell preconditioning with low concentrations of lidocaine (10−15 M) under these conditions, the protective effects of “ineffective” concentrations were detected, because the response amplitude
did not decrease. It was hypothesized that the basic amplitude responses retrieved by lidocaine in a concentration of 10−3 M are memory traces about the effects of this compound in subthreshold concentrations.
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 147, No. 1, pp. 43-46, January, 2009 相似文献
5.
Sokolov OY Pryanikova NA Kost NV Zolotarev YA Ryukert EN Zozulya AA 《Bulletin of experimental biology and medicine》2005,140(5):582-584
Radioreceptor analysis showed that human β-casomorphin-7 displaced 3H-spiperone from 5-HT2-serotonin receptors of the rat cerebral frontal cortex: EC50 8±1 μM. Human and bovine β-casomorphin-7 dose-dependently blocked serotonin-induced human platelet aggregation: IC50 5±1 and 20±4 μM, respectively. It was proved that β-casomorphins-7 act as 5-HT2-serotonin receptor antagonists; one of the mechanisms of their biological effects is presumably associated with modulation
of the serotoninergic system.
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Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 11, pp. 595–597, November, 2005 相似文献
6.
The aim of this study was to define the contribution of renal β2-adrenoceptor (β2-AR) system to regulation of the lipopolysaccharide (LPS) transport system in the kidney of endotoxin-induced septic rats.
Seven-week-old Wistar rats (n = 6/groups) pre-treated with the β2-AR antagonist (ICI118,551: 3.14 μg/kg) or saline were injected with LPS (10 mg/kg i.p.) or saline, and then 24 hours later,
renal function, β2-AR signaling proteins, innate immune proteins, and cytokines were assayed. The injection of LPS depressed creatinine clearance
rate (Ccr) associated with the reduction of renal Gsα and cAMP levels by a single dose of ICI118,551. On the other hand, renal
CD14, toll-like receptor 4(TLR4), and tumour necrosis factor (TNF)-α protein expressions were significantly increased (P < 0.05) by the combination of LPS and ICI118,551. The reduction of Ccr by LPS plus ICI118,551 suggests a possibility that
renal specific up-regulation of the CD14-TLR4-TNF-α signaling cascade by β2-AR inhibition might be involved in sepsis-induced ARF. 相似文献
7.
Lasukova TV Maslov LN Nizkodubova SW Gorbunov AS Zibulnikov SY 《Bulletin of experimental biology and medicine》2009,148(6):877-880
The role of cyclic nucleotides (cAMP, cGMP) and Ca2+-ATPase of the sarcoplasmic reticulum in the mechanism of cardioprotective effects of selective δ1- and κ1-opioid receptor agonists DPDPE and U-50488 was studied under conditions of global ischemia and reperfusion of isolated and
perfused rat heart. Activation of both types of opioid receptors 2-fold reduced the reperfusion release of creatine phosphokinase.
The cardioprotective effect of U-50488 was paralleled by a 2-fold decrease in cAMP content in the myocardium, while DPDPE
did not modify the content of cAMP throughout the experiment. None of these substances changed the content of cGMP in the
myocardium. The cardioprotective effect of DPDPE was not observed after inhibition of sarcoplasmic reticulum Ca2+-ATPase with cyclopiazonic acid. The cardioprotective effect of U-50488 was associated with reduction of cAMP level in the
myocardium, while the cytoprotective effect of DPDPE was mediated by opioidergic modulation of Ca2+ transport at the level of the sarcoplasmic reticulum. 相似文献
8.
Pathogenic hantaviruses selectively inhibit β<Subscript>3</Subscript> integrin directed endothelial cell migration 总被引:5,自引:0,他引:5
Summary. Hantaviruses cause two diseases of man, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS).
Pathogenic and non-pathogenic hantaviruses use β3 and β1 integrins, respectively, to enter endothelial cells. β3 integrins were recently reported to bind receptors that regulate vascular permeability suggesting that hantavirus β3 integrin interactions may regulate endothelial cell function and contribute to viral pathogenesis. In this study we investigated
the ability of pathogenic and non-pathogenic hantaviruses to regulate β3 and β1 integrin directed endothelial cell functions. We found that pathogenic NY-1, SNV, HTN, SEO and PUU viruses blocked endothelial
cell migration on β3, but not β1, integrin ligands. Migration is similarly inhibited by antibodies to β3 integrins which selectively block vitronectin directed endothelial cell migration. As a result, the ability of endothelial
cells to migrate on integrin ligands was selectively inhibited by only pathogenic hantaviruses. Infection by NY-1 virus inhibited
endothelial cell migration as early as 24–48 h post-infection. In contrast, non-pathogenic PH and TUL viruses had no effect
on the ability of endothelial cells to migrate on either β3 or β1 integrin ligands from 1 to 5 days post-infection. These findings indicate that only hantaviruses which use β3 integrins, and are associated with HPS and HFRS diseases, functionally dysregulate endothelial cell migration. These findings
further demonstrate that hantaviruses regulate only β3 integrin directed endothelial cell functions and have no effect on β1 integrin functions. Since β3 integrins are linked to changes in vascular permeability and the maintenance of vascular integrity, these findings suggest
a means by which hantavirus usage and regulation of β3 integrins may contribute to hantavirus pathogenesis.
Received January 23, 2002; accepted May 20, 2002 相似文献
9.
Crutzen R Shlyonsky V Louchami K Virreira M Hupkens E Boom A Sener A Malaisse WJ Beauwens R 《Pflügers Archiv : European journal of physiology》2012,463(2):377-390
NAD(P)H oxidase (NOX)-derived H2O2 was recently proposed to act, in several cells, as the signal mediating the activation of volume-regulated anion channels
(VRAC) under a variety of physiological conditions. The present study aims at investigating whether a similar situation prevails
in insulin-secreting BRIN-BD11 and rat β-cells. Exogenous H2O2 (100 to 200 μM) at basal glucose concentration (1.1 to 2.8 mM) stimulated insulin secretion. The inhibitor of VRAC, 5-nitro-2-(3-phenylpropylamino)-benzoate
(NPPB) inhibited the secretory response to exogenous H2O2. In patch clamp experiments, exogenous H2O2 was observed to stimulate NPPB-sensitive anion channel activity, which induced cell membrane depolarization. Exposure of
the BRIN-BD11 cells to a hypotonic medium caused a detectable increase in intracellular level of reactive oxygen species (ROS)
that was abolished by diphenyleneiodonium chloride (DPI), a universal NOX inhibitor. NOX inhibitors such as DPI and plumbagin
nearly totally inhibited insulin release provoked by exposure of the BRIN-BD11 cells to a hypotonic medium. Preincubation
with two other drugs also abolished hypotonicity-induced insulin release and reduced basal insulin output: 1) N-acetyl-L-cysteine
(NAC), a glutathione precursor that serves as general antioxidant and 2) betulinic acid a compound that almost totally abolished
NOX4 expression. As NPPB, each of these inhibitors (DPI, plumbagin, preincubation with NAC or betulinic acid) strongly reduced
the volume regulatory decrease observed following a hypotonic shock, providing an independent proof that VRAC activation is
mediated by H2O2. Taken together, these data suggest that NOX-derived H2O2 plays a key role in the insulin secretory response of BRIN-BD11 and native β-cells to extracellular hypotonicity. 相似文献
10.
Ceballos A Rabinovich RD Marquina S Fernández Larrosa PN Martinez Peralta L 《Archives of virology》2003,148(3):531-535
Summary. Oxytocin and prostaglandins (PGs) are hormones involved in labor and are used clinically for its induction. In this study
the effect of oxytocin, PGF2α, and PGE2 on Humour immunodeficiency virus-1 production in acutely and persistently infected cells was measured. No significant effect
on p24 antigen production was found with oxytocin or PGs, except for a transient decrease in persistently infected cells treated
with 1 μM PGF2α. These results showed that oxytocin and PGs could be used clinically for labor induction without any direct enhancement in
viral production. Besides, the results with PGF2α at the highest concentration studied may indicate a pharmacological effect.
Received October 10, 2002; accepted October 28, 2002 相似文献
11.
Schaff UY Yamayoshi I Tse T Griffin D Kibathi L Simon SI 《Annals of biomedical engineering》2008,36(4):632-646
Intracellular calcium flux is an early step in the signaling cascade that bridges ligation of selectin and chemokine receptors
to activation of adhesive and motile functions during recruitment on inflamed endothelium. Calcium flux was imaged in real
time and provided a means of correlating signaling events in neutrophils rolling on E-selectin and stimulated by chemokine
in a microfluidic chamber. Integrin dependent neutrophil arrest was triggered by E-selectin tethering and ligation of IL-8
seconds before a rapid rise in intracellular calcium, which was followed by the onset of pseudopod formation. Calcium flux
on rolling neutrophils increased in a shear dependent manner, and served to link integrin adhesion and signaling of cytoskeletally
driven cell polarization. Abolishing calcium influx through membrane expressed store operated calcium channels inhibited activation
of high affinity β2 integrin and subsequent cell arrest. We conclude that calcium influx at the plasma membrane integrates chemotactic and adhesive
signals, and functions to synchronize signaling of neutrophil arrest and migration in a shear stress dependent manner. 相似文献
12.
OBJECTIVE: This study aimed to evaluate the ability of S1319 (4-hydroxy-7-[1-(1-hydroxy-2-methylamino) ethyl]-1,3-benzothiazol-2(3H)-one acetate), a novel beta2-adrenoceptor selective agonist derived from marine sponge, to inhibit IgE-mediated activation of human cultured mast cells (HCMC) in vitro. MATERIALS AND METHODS: We examined the effect of S1319 (racemate) on tryptase release and tumor necrosis factor-alpha (TNF-alpha) production in HCMC generated from human cord blood cells, after cross-linking of high affinity immunoglobulin E receptors (FcepsilonRI), compared with those of the nonselective beta-adrenoceptor agonist, isoproterenol (R-isomer), the selective beta2-adrenoceptor agonist, salbutamol (racemate), and the selective and long-acting beta2-adrenoceptor agonist, formoterol (racemate). We also evaluated the effect of S1319 on the intracellular cAMP level, inositol phosphate production and protein tyrosine phosphorylation in HCMC. RESULTS: S1319 and beta-adrenoceptor agonists inhibited the IgE-mediated release of tryptase. Approximate IC50 values of S1319, formoterol, isoproterenol and albuterol for the inhibition of tryptase release were 0.51+/-0.12, 0.15+/-0.1, 0.80+/-0.09, and 28+/-32.4 nM, respectively. S1319 and beta-adrenoceptor agonists also inhibited TNF-alpha production by HCMC in a concentration-dependent manner. Approximate IC50 values of S1319, formoterol and isoproterenol for the inhibition of TNF-alpha production were 0.19+/-0.03, 0.28+/-0.02 and 0.32+/-0.03 nM, respectively. S1319 caused a concentration-dependent increase in total cell cyclic AMP levels in HCMC. On the other hand, S1319 inhibited the accumulation of inositol 1,4,5-triphosphate and IgE-mediated protein tyrosine phosphorylation of 42-kDa protein, p42 mitogen activated protein (MAP) kinase (ERK-2). CONCLUSION: These results indicate that S 1319 and beta-adrenoceptor agonists are potent inhibitors of the IgE-mediated release of mediators from HCMC. 相似文献
13.
Yu Sun Valeriy Timofeyev Adrienne Dennis Emre Bektik Xiaoping Wan Kenneth R. Laurita Isabelle Deschênes Ronald A. Li Ji-Dong Fu 《Stem cell reviews》2017,13(5):631-643
The inward rectifier potassium current (IK1) is generally thought to suppress cardiac automaticity by hyperpolarizing membrane potential (MP). We recently observed that IK1 could promote the spontaneously-firing automaticity induced by upregulation of pacemaker funny current (If) in adult ventricular cardiomyocytes (CMs). However, the intriguing ability of IK1 to activate If and thereby promote automaticity has not been explored. In this study, we combined mathematical and experimental assays and found that only IK1 and If, at a proper-ratio of densities, were sufficient to generate rhythmic MP-oscillations even in unexcitable cells (i.e. HEK293T cells and undifferentiated mouse embryonic stem cells [ESCs]). We termed this effect IK1-induced If activation. Consistent with previous findings, our electrophysiological recordings observed that around 50% of mouse (m) and human (h) ESC-differentiated CMs could spontaneously fire action potentials (APs). We found that spontaneously-firing ESC-CMs displayed more hyperpolarized maximum diastolic potential and more outward IK1 current than quiescent-yet-excitable m/hESC-CMs. Rather than classical depolarization pacing, quiescent mESC-CMs were able to fire APs spontaneously with an electrode-injected small outward-current that hyperpolarizes MP. The automaticity to spontaneously fire APs was also promoted in quiescent hESC-CMs by an IK1-specific agonist zacopride. In addition, we found that the number of spontaneously-firing m/hESC-CMs was significantly decreased when If was acutely upregulated by Ad-CGI-HCN infection. Our study reveals a novel role of IK1 promoting the development of cardiac automaticity in m/hESC-CMs through a mechanism of IK1-induced If activation and demonstrates a synergistic interaction between IK1 and If that regulates cardiac automaticity. 相似文献
14.
Maslov LN Barzakh EI Krylatov AV Chernysheva GA Krieg T Solenkova NV Lishmanov AY Cybulnikov SY Zhang Y 《Bulletin of experimental biology and medicine》2010,149(5):591-593
The cardioprotective properties of a δ2-opioid receptor agonist deltorphin II were studied in rats with coronary occlusion and reperfusion. Opioid receptor ligands
and inhibitors (glybenclamide, chelerythrine, and 5-hydroxydecanoate) were injected intravenously before ischemia and reperfusion.
A δ2-opioid receptor agonist deltorphin II signifi cantly decreased the infarction zone/risk zone index. This effect was abolished
by naltrexone, naloxone methiodide, and δ2-opioid receptor antagonist naltriben, but not by a δ1-opioid receptor antagonist BNTX. The infarct-limiting effect of deltorphin II was not observed after inhibition of protein
kinase C or blockade of mitochondrial KATP channels. 相似文献
15.
Osikov MV Makarov EV Krivokhizhina LV 《Bulletin of experimental biology and medicine》2007,144(2):178-180
Pathogenesis of hemostasis disorders in septic peritonitis and the possibility of their correction with acute phase protein
(α1-acid glycoprotein; two doses of 150 mg/kg) were experimentally studied on outbred albino rats. Platelets count in the peripheral
blood and their adhesion to endothelium did not change during peritonitis, while aggregation activity increased due to increased
rate and shorter time of aggregation, which was associated with the development of hypercoagulation involving the intrinsic
and common coagulation pathways and reduction of antithrombin activity. α1-Acid glycoprotein increased platelet count above the normal level, normalized aggregation rate, some blood clotting parameters,
and antithrombin activity. Hence, α1-acid glycoprotein is a polyfunctional protein modulating all pathogenetic components in the development of blood clotting
disorders during septic peritonitis.
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 8, pp. 143–145, August, 2007 相似文献
16.
Role of the β<Subscript>1</Subscript>-integrin subunit in the adhesion,extravasation and migration of T24 human bladder carcinoma cells 总被引:2,自引:1,他引:1
Heyder C Gloria-Maercker E Hatzmann W Niggemann B Zänker KS Dittmar T 《Clinical & experimental metastasis》2005,22(2):99-106
The abilities of tumor cells to extravasate from the blood vessel system and to migrate through the connective tissue are prerequisites in metastasis formation. Both processes are chiefly mediated by integrins, which mediate both cell–cell and cell–matrix interactions. We investigated the role of integrin subunits in the adhesion, extravasation and migration of the highly invasive human bladder carcinoma cell line T24. Here we show that inhibition of the β1-integrin subunit using the specific β1-integrin blocking antibody 4B4 significantly reduces the adhesion to HUVEC and transmigratory activity of T24 cells. The blockade of the β1-integrin subunit also resulted in a significantly reduced locomotory activity of T24 cells. A detailed cell migration analysis on a single cell level revealed that blockade of the β1-integrin subunit leads to an altered migration pattern of single cells but does not influence migration per se. Migration parameters such as time active, velocity and distance migrated were significantly reduced as compared to untreated control cells. Our observations strongly suggest a central role for the β1-integrin subunit in forming the cell–cell and cell–matrix bonds necessary for adhesion, extravasation and migration. 相似文献
17.
The effects of ̇raining and/or ageing upon maximal oxygen uptake (O2max) and heart rate values at rest (HRrest) and maximal exercise (HRmax), respectively, suggest a relationship between O2max and the HRmax-to-HRrest ratio which may be of use for indirect testing of O2max. Fick principle calculations supplemented by literature data on maximum-to-rest ratios for stroke volume and the arterio-venous O2 difference suggest that the conversion factor between mass-specific O2max (ml·min–1·kg–1) and HRmax·HRrest
–1 is ~15. In the study we experimentally examined this relationship and evaluated its potential for prediction of O2max. O2max was measured in 46 well-trained men (age 21–51 years) during a treadmill protocol. A subgroup (n=10) demonstrated that the proportionality factor between HRmax·HRrest
–1 and mass-specific O2max was 15.3 (0.7) ml·min–1·kg–1. Using this value, O2max in the remaining 36 individuals could be estimated with an SEE of 0.21 l·min–1 or 2.7 ml·min–1·kg–1 (~4.5%). This compares favourably with other common indirect tests. When replacing measured HRmax with an age-predicted one, SEE was 0.37 l·min–1 and 4.7 ml·min–1·kg–1 (~7.8%), which is still comparable with other indirect tests. We conclude that the HRmax-to-HRrest ratio may provide a tool for estimation of O2max in well-trained men. The applicability of the test principle in relation to other groups will have to await direct validation. O2max can be estimated indirectly from the measured HRmax-to-HRrest ratio with an accuracy that compares favourably with that of other common indirect tests. The results also suggest that the test may be of use for O2max estimation based on resting measurements alone.An erratum to this article can be found at 相似文献
18.
Lasukova TV Maslov LN Platonov AA Guzarova NV Lishmanov YB 《Bulletin of experimental biology and medicine》2007,143(1):22-25
The cardioprotective and antiarrhythmic effects of a selective κ1-opioid receptor agonist U-50,488 were studied during experimental 45-min total ischemia and 30-min reperfusion of isolated
rat heart. The opioid had no effect on the incidence and type of reperfusion arrhythmias. U-50,488 in a concentration of 0.1
μM inhibited reperfusion-induced release of creatine phosphokinase and decreased cAMP concentration in the myocardium by 2
times. These parameters remained unchanged after treatment with U-50,488 in a concentration of 1 μM. The cardioprotective
effect of U-50,488 was probably associated with a decrease in cAMP concentration in heart cells. U-50,488 in a concentration
of 1 μM produced no cardioprotective effect, which can be explained by its interaction with an unknown non-opioid receptor
in cardiomyocytes.
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 1, pp. 28–31, January, 2007 相似文献
19.
Effect of an α<Subscript>1</Subscript>-adrenergic blocker on plasticity elicited by motor training 总被引:1,自引:0,他引:1
Sawaki L Werhahn KJ Barco R Kopylev L Cohen LG 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2003,148(4):504-508
Recovery of motor function elicited by motor training after cortical lesions in rats is enhanced by norepinephrine (neurotransmitter
mediating α1-adrenergic function) and downregulated by α1-adrenergic antagonists. In spite of this, α1-adrenergic antagonists are used to treat elderly patients with hypertension and prostate hyperplasia in stroke settings.
The purpose of this study was to determine the effects of a single oral dose of the α1-adrenergic antagonist prazosin on training-dependent plasticity in intact humans, a function thought to contribute to recovery
of motor function after cortical lesions. We report that prazosin decreased the ability of motor training to elicit training-dependent
plasticity relative to a drug-free condition. These data suggest caution when using α1-adrenergic blockers in rehabilitative clinical settings following brain lesions.
Electronic Publication 相似文献
20.
Koppo K Whipp BJ Jones AM Aeyels D Bouckaert J 《European journal of applied physiology》2004,93(3):366-373
We have previously observed that following the onset of moderate intensity cycle ergometry, the pulmonary O2 uptake (O2) in trained cyclists often does not increase towards its steady-state value with the typical mono-exponential characteristics; rather, there is a transient overshoot. The purpose of this study was to systematically examine this phenomenon by comparing the O2responses to two moderate-intensity work rates and one high-intensity work rate in trained and untrained subjects. Following a ramp exercise test to the limit of tolerance for the determination of the gas exchange threshold (GET) and O2peak, seven trained cyclists [mean (SD); O2peak 66.6 (2.5) ml·kg–1·min–1] and eight sedentary subjects [O2peak 42.9 (5.1) ml·kg–1·min–1] completed six step transitions from baseline cycling to work rates requiring 60% and 80% GET and three step transitions from baseline cycling to a work rate requiring 50% of the difference between GET and O2peak (50%). O2 was measured breath-by-breath and modelled using standard techniques. The sedentary subjects did not overshoot the steady-state O2 at any intensity. At 60% GET, six of the seven cyclists overshot the steady-state O2 [by an integral volume of 164 (44) ml between ~45 and 125 s]. At 80% GET, four of the seven cyclists overshot the steady-state O2 [by an integral volume of 185 (92) ml between ~55 and 140 s]. None of the cyclists showed an overshoot at 50%. These results indicate that trained cyclists evidence an overshoot in O2 before steady-state is reached in the transition to moderate-intensity exercise. The mechanism(s) responsible for this effect remains to be elucidated, as does whether the overshoot confers any functional or performance benefit to the trained cyclist. 相似文献