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Background: Whether yoga is effective in the cardiac rehabilitation of people with coronary artery disease (CAD) remains controversial. Objective: The aim of this study was to investigate the effects of yoga intervention on psychological symptoms, health-related quality of life (HRQoL), and major cardiovascular risk factors in people with CAD. Methods: We searched MEDLINE/PubMed, Cochrane, EMBASE, and Physiotherapy Evidence Database (from the earliest date available to July 2023). Mean difference (MD), standardized MD (SMD), and 95% confidence interval (CI) were calculated. Results: Seventeen studies, with 5,698 patients, met the study criteria. Compared to control (no exercise), yoga resulted in improved depression MD −0.83 (95% CI: −1.35 to −0.31), stress MD −3.83 (95% CI: −4.8 to 2.86), HRQoL SMD 1.48 (95% CI: 0.55 to 2.4), major cardiovascular risk factors (peak VO2 MD 1.7 mL/kg/min [95% CI: 0.2 to 3.3], systolic blood pressure MD −3.2 mmHg [95% CI: −5.9 to −0.5], and diastolic blood pressure MD −2.42 mmHg [95% CI: −4.08 to −0.76]). Conclusions: Yoga was effective in the improvement of psychological symptoms, HRQoL, and cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Background: Exercise is an important component of rehabilitation care for people with coronary heart disease (CHD). Objectives: The aim of this study was to critically analyze and summarize the existing evidence from published systematic reviews (SRs) and meta-analyses of randomized controlled trials (RCTs) that have evaluated the effects of different types of exercise interventions on cardiorespiratory fitness, as measured by peak oxygen consumption in people with CHD. Methods: Electronic databases (Cochrane Library, Medline/PubMed, EMBASE, and PEDro) were searched for SRs of exercise interventions of people with CHD. Two reviewers assessed the quality of SRs using the AMSTAR-2 tool and evaluated the strength of evidence quality with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system for relevant outcome measures. Mean difference (MD) and 95% confidence intervals (CIs) were calculated. Results: Thirty-one SRs (with 125 RCTs) met the study criteria, including 33,608 patients. Compared with usual care, continuous aerobic exercise produced an improvement in peak oxygen consumption, MD of 3.8 mL kg−1 min−1 (95% CI: 3.204.4, I2 = 67%); high-intensity interval training, MD 6.1 mL kg−1 min−1 (95% CI: 0.4–11.8, I2 = 97%); resistance training, MD of 2.1 mL kg−1 min−1 (95% CI: 0.98–3.2, I2 = 60%); combined aerobic and resistance training, MD of 3.0 mL kg−1 min−1 (95% CI: 2.5–3.4, I2 = 0%); and water-based exercise, MD of 4.4 mL kg−1 min−1 (95% CI, 2.1–6.7; I2 = 2%). Conclusion: Exercise interventions improve peak oxygen consumption in people with CHD. However, there was moderate to very-low certainty for the evidence found. [ABSTRACT FROM AUTHOR]

Objective: This systematic review and meta-analysis aimed to analyze the published randomized controlled trials (RCTs) that investigated the effects of exercise interventions on functioning and health-related quality of life following hospital discharge for recovery from critical illness. Design: Systematic review and meta-analysis of RCTs. Data sources: We searched PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, PEDro data base, and SciELO (from the earliest date available to January 2023) for RCTs that evaluated the effects of physical rehabilitation interventions following hospital discharge for recovery from critical illness. Review methods: Study quality was evaluated using the PEDro Scale. Mean differences (MDs), standard MDs (SMD), and 95% confidence intervals (CIs) were calculated. Results: Fourteen studies met the study criteria, including 1259 patients. Exercise interventions improved aerobic capacity SMD 0.2 (95% CI: 0.03–0.3, I 2 = 0% N = 880, nine studies, high-quality evidence), and physical component score of health-related quality of life MD 3.3 (95% CI: 1.0–5.6, I 2 = 57%, six studies N = 669, moderate-quality evidence). In addition, a significant reduction in depression was observed MD −1.4 (95% CI: −2.7 to −0.1, I 2 = 0% N = 148, three studies, moderate-quality evidence). No serious adverse events were reported. Conclusion: Exercise intervention was associated with improvement of aerobic capacity, depression, and physical component score of health-related quality of life after hospital discharge for survivors of critical illness. [ABSTRACT FROM AUTHOR]

Background. There is a growing use of water-based exercises in cardiac rehabilitation programs. However, there is little data concerning the effects of water-based exercise on the exercise capacity of coronary artery disease (CAD) patients. Objective. To perform a systematic review to investigate the effects of water-based exercise on peak oxygen consumption, exercise time, and muscle strength in patients with CAD. Methods. Five databases were searched to find randomized controlled trials that evaluated the effects of water-based exercise for coronary artery disease patients. Mean differences (MD) and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed using the I 2 test. Results. Eight studies were included. Water-based exercise resulted in an improvement in peak VO2 of 3.4 mL/kg/min (95% CI, 2.3 to 4.5; I 2 = 0 %; 5 studies, N = 167), exercise time of 0.6 (95% CI, 0.1 to 1.1; I 2 = 0 %; 3 studies, N = 69), and total body strength of 32.2 kg (95% CI, 23.9 to 40.7; I 2 = 3 %; 3 studies, N = 69) when compared to no exercising controls. Water-based exercise resulted in an improvement in peak VO2 of 3.1 mL/kg/min (95% CI, 1.4 to 4.7; I 2 = 13 %; 2 studies, N = 74), when compared to the plus land exercise group. No significant difference in peak VO2 was found for participants in the water-based exercise plus land exercise group compared with the land exercise group. Conclusions. Water-based exercise may improve exercise capacity and should be considered as an alternative method in the rehabilitation of patients with CAD. [ABSTRACT FROM AUTHOR]

Objective The purpose of this study was to compare high-intensity interval training (HIIT) with moderate-intensity continuous training (MICT) for feasibility, safety, adherence, and short- and long-term efficacy in improving functioning and health-related quality of life in survivors of coronavirus disease 2019 (COVID-19). Methods COVIDEX is a two-pronged, parallel-group, randomized controlled trial with an 8-week training intervention. The study participants will be 94 patients aged >18 years, admitted to a specialized post-COVID center. Participants will be randomized to HIIT (4 × 4 minutes of high-intensity work periods at 85% to 90% of peak heart rate) and MICT (47 minutes at 70% to 75% peak heart rate) groups for biweekly sessions for 8 weeks. The participants will undergo 2 phases of supervised training (phases 1 and 2) of 4 weeks each, in a public, specialized, post-COVID center. In phase 1, we will assess and compare the feasibility, acceptability, and short-term efficacy of HIIT and MICT intervention. In phase 2, the long-term efficacy of HIIT and MICT will be assessed and compared regarding function and health-related quality of life. To prevent any expectation bias, all study participants and assessors will be blinded to the study hypotheses. Group allocation will be masked during the analysis. All statistical analyses will be conducted following intention-to-treat principles. Impact This study is the first randomized controlled trial that will compare the feasibility, safety, adherence, and efficacy of the HIIT and MICT intervention programs in this population. The findings will potentially provide important information and assist in clinical decision making on exercise to optimize the benefits of clinical health care in survivors of COVID-19. [ABSTRACT FROM AUTHOR]

Background: Respiratory dysfunctions are an important cause of morbidity and death in cerebral palsy (CP) populations. Respiratory exercises in addition to conventional rehabilitation have been suggested to improve respiratory status in CP patients. The objective of this systematic review and meta-analysis was to verify the effects of the addition of respiratory exercises to conventional rehabilitation on pulmonary function, functional capacity, respiratory muscle strength, gross motor function and quality of life in children and adolescents with CP. Methods: We searched for randomized controlled clinical trials in PubMed/Medline, Lilacs, SciELO, EMBASE and Physiotheraphy Evidence (PEDro) from their inception until July 2022 without language restrictions. Studies that included respiratory exercises (breathing exercise program; feedback respiratory training; incentive spirometer exercise; inspiratory muscle training; and combination of respiratory exercises + incentive spirometer exercise) in combination with conventional rehabilitation for children and adolescents with CP were evaluated by two independent reviewers. The mean difference (MD) and 95% confidence interval (CI) were estimated by random effect models. Results: Ten studies met the eligibility criteria, including 324 children aged from 6 to 16 years. The meta-analysis showed an improvement in inspiratory muscle strength of 22.96 cmH2O (18.63–27.27, n = 55) and pulmonary function of 0.60 (0.38–0.82, n = 98) for forced vital capacity (L); 0.22 (0.06–0.39, n = 98) for forced expiratory volume at 1 second (L); and 0.50 (0.05–0.04, n = 98) for peak expiratory flow (L/min). Functional skills in daily living activities improved in the intervention group. Caregivers' assistance of daily living activities, functional capacity, gross motor function and expiratory muscle strength showed a nonsignificant improvement. Social well-being and acceptance and functioning domains improved in only one study. Conclusions: Emerging data show significant enhancements in inspiratory muscle strength and pulmonary function in CP patients after respiratory training in addition to conventional rehabilitation. There is no consensus on the frequency, type or intensity of respiratory exercises for children with and adolescents with CP. [ABSTRACT FROM AUTHOR]

Objective Exercise is a recommended component of care for people living with HIV/AIDS; however, it is unclear which type of exercise is most effective. The purpose of this study was to investigate the relative effects of different types of exercise interventions on aerobic capacity measured by peak oxygen consumption (peak VO2) and health-related quality of life (HRQoL) in this population. Methods For this systematic review and indirect-comparisons meta-analysis (network meta-analysis), different electronic databases were searched up to February 2020 for randomized controlled trials that evaluated the effects of different types of exercise interventions on peak VO2 and HRQoL of people living with HIV/AIDS. Mean differences, standardized mean difference (SMD), and 95% CI were calculated. Fixed- and random-effects Bayesian network meta-analysis were used to compare the relative effectiveness of the different exercise interventions. Results Forty studies met the study criteria, reporting on a total of 1518 patients. When comparing the exercise interventions with usual care (control group) for the peak VO2 outcome, combined aerobic and resistance exercise was the highest ranked exercise intervention with an SMD of 4.2 (95% CI = 2.5 to 5.9), followed by aerobic exercise (SMD = 3.1; 95% CI = 1.4 to 5.1). Compared with aerobic exercise, resistance training, and yoga, combined aerobic and resistance exercise was the best exercise intervention to promote improvement on physical function, general health, mental health, and energy/vitality domains HRQoL. Conclusion The combined aerobic and resistance exercise was the highest ranked exercise intervention to improve peak VO2 and HRQoL. Combined aerobic and resistance exercise should be considered as a component of care for people living with HIV/AIDS. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effects of the water-based exercise on balance, mobility, mobility and functional independence, functional performance, fear of falling and quality of life in people with Parkinson's disease. Methods: We searched pubmed/MEDLINE, Cochrane Central Register of Controlled Trials, PEDro data base and SciELO to June 2020 for randomised controlled trials that investigated the effects of water-based exercise in people with Parkinson's disease. Two comparisons were made: water-based exercise versus usual care and water-based exercise versus land-exercise. The main outcomes were Balance, Confidence, Mobility, Unified Parkinson's Disease Rating Scale and quality of life. Mean differences (MD) with 95% confidence interval (CI) were calculated, and heterogeneity was assessed using the I 2 test. Results: Fifteen randomised controlled trials were found (435 people). Compared to usual care, water-based exercise resulted in improvement in balance MD (9.1, 95% CI: 6.5, 11.8, N = 45). Water-based exercise resulted in improvement in balance MD (3.1, 95% CI: 1.2, 5.0, N = 179), mobility MD (−2.2, 95% CI: −3.3, −1.0, N = 197) and quality of life MD (−5.5, 95% CI: −11, −0.07, N = 98) compared to land-based exercise, but without significant difference in functional performance MD (0.01, 95% CI: −2.6 to 2.7, N = 69). Land-based exercise resulted in improvement in fear of falling MD (−3.5, 95% CI: −5.6, −1.3, N = 58) compared to water-based exercise. Conclusion: Water-based exercise was more efficient than land-based exercise and/or usual care in improving balance, mobility and quality of life in people with Parkinson's disease. [ABSTRACT FROM AUTHOR]

The dose of progressive active mobilization is still uncertain. The purpose of this study is to identify if the addition of a protocol of progressive active mobilization with dose and training load control to usual care is effective in reducing the length of stay in intensive care unit (ICU) and the improvement of the functioning, incidence of ICU-acquired weakness (ICUAW), mechanical ventilation duration and mortality rate in patients hospitalized in ICU. It is Double-blind randomised clinical trial. The setting for this trial will be medical and surgical ICU of a university hospital. The study participants will be 118 patients aged> 18 years admitted to ICU for less than 72 hours. Participants will be randomized to either an experimental or control group. The experimental group will undertake addition of a protocol of progressive active mobilization with dose and training load control to usual care, while the control group will undertake only usual care. The primary outcome will be length of ICU stay. The secondary outcomes will be Cross-sectional area and muscle thickness of the rectus femoris and biceps brachii, Change in muscle strength from the baseline, Functional Status, incidence of ICUAW, Days with mechanical ventilation and Mortality. All statistical analyses will be conducted following intention-to-treat principles. It has a detailed description of the dose of exercise, was designed with the strictest methodological criteria. These characteristics allow to investigate with greater certainty the results progressive active mobilization in critical patients, allowing replication and future combinations in meta-analyzes. [ABSTRACT FROM AUTHOR]

We performed a systematic review and meta-analysis to investigate the effects of facilitated tucking position during painful procedure in pain management of preterm infants. We searched MEDLINE, PEDro, SciELO and the Cochrane Library (until June 2019) for randomized controlled trials. An α value ≤ 0.05 was considered significant. Heterogeneity among studies was examined with Cochran's Q and I2 statistic, in which values greater than 40% were considered indicative of high heterogeneity and random-effects model was chosen. Analyses were performed with Review Manager 5.3. Fifteen studies met the eligibility criteria, including 664 preterm infants. The meta-analyses showed a significant reduction in pain of - 1.02 (95% CI - 1.7 to - 0.4, N = 216) during endotraqueal suctioning for participants in the facilitated tucking position group (FTPG) compared with routine care group. The meta-analyses showed a non-significant difference in pain - 0.3 (95% CI - 2.05 to - 1.4, N = 88) during heel stick for participants in the FTPG compared with oral glucose group. The meta-analyses showed a non-significant difference in pain for participants in the FTPG compared with oral opioid group 0.2 (95% CI - 1.4 to 1.8, N = 140).Conclusion: Facilitated tucking position may improve the pain during painful procedures.What is Known:• Exposure of premature babies to painful procedures is associated with changes in brain development, regardless of other factors.• Facilitated tucking reduces the expression of pain in premature infants.What is New:• Facilitated tucking position was efficient in pain management of preterm infants when compared to routine care.• Facilitated tucking compared to opioid or oral glucose did not achieve a significant reduction in pain intensity. [ABSTRACT FROM AUTHOR]

The physical activity and sport are key elements for a healthy lifestyle. However, a little-investigated element is the presence of a possible relationship between school or academic performance and the participation in physical activity and sport in groups of preadolescents and adolescents. In order to clarify the complex relationship between mind and body in preadolescence and adolescence, the present discussion investigates the causal and direct relationship between sport activity and performance; and describes how this relationship can be mediated by the sense of self-esteem and self-efficacy; and investigates the relationship between group sports practice and school or academic performance. [ABSTRACT FROM AUTHOR]

The human being can be divided into body and mind, two inextricably linked aspects influencing each other. From birth, the body is the site of emotional experiences thanks to cellular memory. The transgenerational and the oneiric imaginary are two themes closely related to the body. Many families express their emotional experiences through bodily symptoms and, in dreams, body icons are used to "talk" about the subject's identity. The body expresses itself and "speaks" through dreams, which can even become predictors of diseases. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of upper limb resistance exercise on the functional capacity, muscle function, and quality of life in patients with chronic obstructive pulmonary disease. Setting: Clinical School of Physiotherapy in a Public University of Brazil. Subjects: 58 patients were recruited; of these, 7 were excluded and 51 individuals were enrolled. Intervention: Control group performed warm-up, aerobic exercise, inspiratory muscle training, and session stretching, followed by massage therapy. The treatment group performed warm-up, aerobic exercise, inspiratory muscle training, three sets of upper limb resistance exercise, and session stretching, followed by massage therapy. Total three sessions per week for eight weeks. Primary outcome measures: 6-minute walk test, respiratory and peripheral muscle strength, dyspnea, and quality of life. Normality of the data was tested using the Shapiro–Wilk test; paired analysis of variance was used for intergroup analyses. Results: 51 patients (25 in the control group and 26 in the treatment group); 41% of the subjects were men. Mean forced expiratory volume was 2.6 ± 0.6 L, and mean body mass index was 27.3 ± 7.0 kg/m2. The upper limb resistance exercise resulted in significantly greater benefit in terms of exercise capacity (88.5 ± 81.9 m, P = 0.043), inspiratory muscle strength (22.9 ± 24.2 cm H2O, P = 0.001), upper limb muscle strength (2.3 ± 3.1 kg, P = 0.027), and quality of life scores (−15.3 ± 10.9 points, P = 0.000). Conclusion: Upper limb resistance exercise improved the exercise capacity, respiratory muscle strength, and quality of life. [ABSTRACT FROM AUTHOR]

Objective: To determine the effects of different intradialytic exercise training modalities on physical functioning and health-related quality of life of maintenance hemodialysis patients. Methods: We searched MEDLINE, Cochrane Trials Register and CINAHL for controlled trials that evaluated the effects of intradialytic exercise training for maintenance hemodialysis patients and published from the earliest available date to December 2017. Weighted mean difference and 95% confidence interval (CI) were calculated, and heterogeneity was assessed using the I2 test. Results: Fifty-six studies met the study criteria, comprising a total of 2586 patients. Compared with no exercise, combined aerobic and resistance exercise resulted in significant improvement in peak VO2 weighted mean difference (5.1 mL kg−1 min−1; 95% CI: 3.4, 6.8 mL kg−1 min−1), depression symptoms (−7.32; 95% CI −9.31, −5.33) and both physical function (10.67 points; 95% CI 1.08, 20.25 points) and vitality (10.01 points; 95% CI 4.30, 15.72 points) domains of health-related quality of life. Resistance exercise alone was significantly associated with improvement in the 6-minute walk test distance (30.2 m; 95% CI 24.6, 35.9 m), knee extensor strength (0.6 N; 95% CI 0.1, 1.0 N) and Physical Component Score of health-related quality of life (9.53 points; 95% CI −3.09, 22.15 points) when compared with control group. Aerobic exercise alone was not significantly associated with aerobic capacity and quality of life improvement. Conclusion: The results provide support to interventions that combine intradialytic aerobic and resistance exercises to improve physical functioning and quality of life in end-stage renal disease patients undergoing hemodialysis. [ABSTRACT FROM AUTHOR]

Objective: To assess whether the addition of an education programme for primary caregivers to rehabilitation improves daily functioning in children with cerebral palsy. Design: A randomized, single-blind, controlled study. Setting: This study was conducted in a rehabilitation centre in Salvador, Brazil. Participants: A total of 63 boys and girls with cerebral palsy, at 1–12 years of age, with Gross Motor Function Classification Systems I–V, were randomly assigned to two groups: educational programme for primary caregivers and conventional rehabilitation (n = 29) or conventional rehabilitation alone (n = 31). Intervention: Each group received 12 sessions of 30 minutes of conventional rehabilitation and 12 sessions of 45 minutes to intervention group. Measurements: Gross Motor Function Classification System, Gross Motor Function Measure and daily functioning with the Pediatric Evaluation of Disability Inventory were assessed by a blinded assessor. The clinical outcomes were obtained at the completion of treatment (12 weeks). Results: Of the 63 patients included, 60 (mean ± SD age: 4.6 ± 2.74 years) completed the protocol. The combined education and rehabilitation, as compared with conventional rehabilitation alone, yielded significantly greater benefit in the self-care domain of the Functional Skills Scale (mean change 1.74 versus 5; P = 0.001), self-care (mean change 5.52 versus 13.99; P = 0.017) and the mobility domain of the Caregiver Assistance Scale of Pediatric Evaluation of Disability Inventory (mean change 0.87 versus 17.88; P = 0.002). Conclusion: Self-care and mobility improved in children with cerebral palsy with the addition to conventional rehabilitation of an educational programme for primary caregivers. [ABSTRACT FROM AUTHOR]

To better understand T lymphocyte costimulation by inducible costimulator (ICOS; H4; CD278), we analyzed proteins binding to ICOS peptides phosphorylated at the YMFM motif. Phosphorylated ICOS binds class IA phosphatidyl inositol 3-kinase (PI3-K) p85α, p50-55α and p85β regulatory subunits and p110α, p110δ and p110β catalytic subunits. Intriguingly, T cells expressed high levels of both p110α or p110δ catalytic subunits, yet ICOS peptides, cell surface ICOS or PI3-kinase class IA regulatory subunits preferentially coprecipitated p110α catalytic subunits. Silencing p110α or p110δ partially inhibited Akt/PKB activation induced by anti-CD3 plus anti-ICOS antibodies. However, silencing p110α enhanced and silencing p110δ inhibited Erk activation. Both p110α- and p110δ-specific inhibitors blocked cytokine secretion induced by TCR/CD3 activation with or without ICOS costimulus, but only p110α inhibitors blocked ICOS-induced cell elongation. Thus, p110α and p110δ are essential to optimal T cell activation, but their abundance and activity differentially tune up distinct ICOS signaling pathways. [ABSTRACT FROM AUTHOR]

Perforin is involved in cell-mediated cytotoxicity and mutations of its gene (PRF1) cause familial hemophagocytic lymphohistiocytosis (FLH2). PRF1 sequencing in 190 patients with multiple sclerosis and 268 controls detected two FLH2-associated variations (A91V, N252S) in both groups and six novel mutations (C999T, G1065A, G1428A, A1620G, G719A, C1069T) in patients. All together, carriers of these variations were more frequent in patients than in controls (phenotype frequency: 17 vs 9%, P=0.0166; odds ratio (OR)=2.06, 95% confidence interval (CI): 1.13–3.77). Although A91V was the most frequent variation and displayed a trend of association with multiple sclerosis (MS) in the first population of patients and controls (frequency of the 91V allele: 0.076 vs 0.043, P=0.044), we used it as a marker to confirm PRF1 involvement in MS and assessed its frequency in a second population of 966 patients and 1520 controls. Frequency of the 91V allele was significantly higher in patients than in controls also in the second population (0.075 vs 0.058%, P=0.019). In the combined cohorts of 1156 patients and 1788 controls, presence of the 91V allele in single or double dose conferred an OR=1.38 (95% CI=1.10–1.74). These data suggest that A91V and possibly other perforin variations indicate susceptibility to MS.Genes and Immunity (2008) 9, 438–444; doi:10.1038/gene.2008.35; published online 22 May 2008 [ABSTRACT FROM AUTHOR]

Several sets of data indicate that ICOS regulates cytokine production in activated T cells, but is less effective on naïve T cells. This work evaluates ICOS function in human naïve CD4 T cells through an assessment of the effect of soluble forms of the ICOS and CD28 physiological ligands on activation driven by anti-CD3 mAb. ICOS strikingly potentiated secretion of IL-2, IFN-γ, IL-10, and TNF-α, but not IL-4, promoted by optimal stimulation of CD3+CD28, and it was the key switching-factor of activation when cells received suboptimal stimulation of CD3+CD28 or stimulation of CD3 alone in the presence of exogenous IL-2. In these conditions, blockade of IL-2 and IFN-γ showed that ICOS builds up a positive feedback loop with IFN-γ, which required IL-2 and was inhibited by IL-4. By contrast, in the absence of CD28 triggering or exogenous IL-2, ICOS-induced costimulation mainly supported expression of TGF-β1 and FoxP3 and differentiation of regulatory T cells capable to inhibit proliferation of naïve CD4 T cells driven by allogeneic cells. These data suggest that ICOS favors differentiation of Th effector cells when cooperates with appropriate activation stimuli such as CD3+CD28 or CD3+IL-2, whereas it supports differentiation of regulatory T cells when costimulatory signals are insufficient. [ABSTRACT FROM AUTHOR]

Substance P (SP) is deeply involved in lung pathophysiology and plays a key role in the modulation of inflammatory-immune processes. We previously demonstrated that SP activates guinea-pig alveolar macrophages (AMs) and human monocytes, but a careful examination of its effects on human AMs is still scarce.This study was undertaken to establish the role of SP in human AM isolated from healthy smokers and non-smokers, by evaluating the presence of tachykinin NK1 receptors (NK-1R) and SP's ability to induce superoxide anion (O2-) production and cytokine release, as well as activation of the nuclear factor-?B (NF-?B) pathway.By Western blot analysis and immunofluorescence, we demonstrate that authentic NK-1R are present on human AMs, a three-fold enhanced expression being observed in healthy smokers. These NK-1R are functional, as SP and NK1 agonists dose-dependently induce O2- production and cytokine release. In AMs from healthy smokers, SP evokes an enhanced respiratory burst and a significantly increased release of tumor necrosis factor-aas compared to healthy non-smokers, but has inconsistent effects on IL-10 release. The NK1 selective antagonist CP 96,345 ((2S,3S)-cis-2-diphenylmethyl-N[(2-methoxyphenyl)-methyl]-1-azabicyclo-octan-3-amine)) competitively antagonized SP-induced effects.SP activates the transcription factor NF-?B, a three-fold increased nuclear translocation being observed in AMs from healthy smokers. This effect is receptor-mediated, as it is reproduced by the NK1 selective agonist[Sar9Met(O2)11]SP and reverted by CP 96,345.These results clearly indicate that human AMs possess functional NK-1R on their surface, which are upregulated in healthy smokers, providing new insights on the mechanisms involved in tobacco smoke toxicity.British Journal of Pharmacology (2005) 145, 385-396. doi:10.1038/sj.bjp.0706198 Published online 21 March 2005 [ABSTRACT FROM AUTHOR]