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1.
J Strength Cond Res ; 37(12): 2457-2466, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38015735

RESUMO

ABSTRACT: Langford, EL, Bergstrom, HC, Lanham, S, Eastman, AQ, Best, S, Ma, X, Mason, MR, and Abel, MG. Evaluation of work efficiency in structural firefighters. J Strength Cond Res 37(12): 2457-2466, 2023-To perform occupational tasks safely and effectively, firefighters (FF) must work quickly and consume air provided by the self-contained breathing apparatus (SCBA) efficiently. However, most literature only factors work rate into performance, neglecting the inherent time limitation imposed by the SCBA. The purpose of this article was to (a) evaluate the reliability and variability in a "work efficiency" (WE) performance metric reflective of both work rate and air consumption; (b) explore the relationship between WE and established measures of metabolic strain; and (c) identify fitness, anthropometric, and demographic correlates of WE. About 79 structural FF completed an air consumption drill while breathing through an SCBA. Self-paced work duration and air consumption were entered into the WE equation. A subsample of FF (n = 44) completed another randomized trial while breathing through a portable gas analyzer. Anthropometric and fitness data were collected separately. Correlations were performed between WE vs. fitness, anthropometric, demographic, and metabolic outcomes. Multiple linear regression was used to identify the strongest predictors of WE. WE was reliable (intraclass correlation coefficient = 0.71) and yielded inter-FF variability {0.79 ± 0.25 ([lb·in-2·min]-1) × 104; coefficient of variation = 31.6%}. WE was positively correlated to oxygen consumption (V̇O2) (L·minute-1, mL·kg-1·minute-1) and tidal volume and negatively correlated to V̇E/V̇O2 and respiratory frequency. Height, upper-body endurance, and aerobic endurance were identified as the strongest predictors of WE (adjusted R2 = 0.59, RMSE = 0.16). WE is a reliable and occupationally relevant method to assess FF performance because it accounts for work rate and air consumption. Firefighters may enhance WE through a training intervention focused on improving metabolic tolerance, upper-body endurance, and aerobic endurance.


Assuntos
Bombeiros , Dispositivos de Proteção Respiratória , Humanos , Reprodutibilidade dos Testes , Exercício Físico , Respiração
2.
Bioorg Med Chem Lett ; 65: 128648, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35231579

RESUMO

There is an increasingly urgent and unmet medical need for novel antibiotic drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. Novel bacterial type II topoisomerase inhibitors (NBTIs) are of high interest due to limited cross-resistance with fluoroquinolones, however analogues with Gram-negative activity often suffer from hERG channel inhibition. A novel series of bicyclic-oxazolidinone inhibitors of bacterial type II topoisomerase were identified which display potent broad-spectrum anti-bacterial activity, including against MDR strains, along with an encouraging in vitro safety profile. In vivo proof of concept was achieved in a A. baumannii mouse thigh infection model.


Assuntos
Oxazolidinonas , Inibidores da Topoisomerase , Animais , Antibacterianos/farmacologia , DNA Girase/metabolismo , Fluoroquinolonas/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Oxazolidinonas/farmacologia , Relação Estrutura-Atividade , Inibidores da Topoisomerase II/farmacologia , Inibidores da Topoisomerase/farmacologia
3.
Clin Auton Res ; 32(6): 485-495, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36394777

RESUMO

Normal pregnancy is associated with vast adjustments in cardiovascular autonomic control. Sympathetic baroreflex sensitivity has been reported to be attenuated during pregnancy in animal models, but most studies in humans are cross-sectional and findings from longitudinal case studies are inconclusive. It remains unclear how sympathetic baroreflex sensitivity is altered longitudinally during pregnancy within an individual in different body postures. Therefore, this study examined the impact of posture on sympathetic baroreflex sensitivity in 24 normal-weight normotensive pregnant women. Spontaneous sympathetic baroreflex sensitivity was assessed during early (6-11 weeks) and late (32-36 weeks) pregnancy and 6-10 weeks postpartum in the supine posture and graded head-up tilt (30° and 60°). In addition, data from the postpartum period were compared with (and no different to) 18 age-matched non-pregnant women to confirm that the postpartum period was reflective of a non-pregnant condition (online supplement). When compared with postpartum (-3.8 ± 0.4 bursts/100 heartbeats/mmHg), supine sympathetic baroreflex sensitivity was augmented during early pregnancy (-5.9 ± 0.4 bursts/100 heartbeats/mmHg, P < 0.001). However, sympathetic baroreflex sensitivity at 30° or 60° head-up tilt was not different between any phase of gestation (P > 0.05). When compared to supine, sympathetic baroreflex sensitivity at 60° head-up tilt was significantly blunted during early (Δ2.0 ± 0.7 bursts/100 heartbeats/mmHg, P = 0.024) and late (Δ1.5 ± 0.6 bursts/100 heartbeats/mmHg, P = 0.049) pregnancy but did not change postpartum (Δ0.4 ± 0.6 bursts/100 heartbeats/mmHg, P = 1.0). These data show that time-course changes in sympathetic baroreflex sensitivity are dependent on the posture it is examined in and provides a foundation of normal blood pressure regulation during pregnancy for future studies in women at risk for adverse pregnancy outcomes.


Assuntos
Barorreflexo , Postura , Animais , Gravidez , Feminino , Humanos , Estudos Transversais , Frequência Cardíaca , Sistema Nervoso Autônomo
4.
Am J Physiol Regul Integr Comp Physiol ; 320(3): R307-R316, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33438516

RESUMO

Excessive salt intake is considered a risk factor for the development of hypertension. Additionally, aberrant neurocirculatory responses to a cold stimulus are associated with an increased risk of hypertension. This study aimed to determine whether salt loading versus salt reduction would impact hemodynamic and sympathetic neural responses during the cold pressor test (CPT) in premenopausal women with a history of normal pregnancy. Nine healthy premenopausal women [42 ± 3 (SD) yr] were given a standardized isocaloric high-salt (HS; 250 mEq sodium/day) or low-salt (LS; 50 mEq sodium/day) diet for 1-wk each (∼2 mo apart with the order randomized), while water intake was ad libitum. Laboratory testing was performed following each HS and LS period in the mid-luteal phase of the menstrual cycle. Subjects were in the supine position and beat-by-beat blood pressure (BP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were continuously measured during 1-min baseline followed by 2-min CPT, and 3-min recovery. BP and HR increased during the CPT (both P < 0.001); the responses were similar between HS and LS. MSNA increased during the CPT, but the increment (Δ) was greater during HS than LS (29 ± 6 vs. 15 ± 4 bursts/min; P < 0.001). The transduction of MSNA for vasoconstriction during the CPT was lower in HS (P < 0.05). Thus, salt loading augments sympathetic neural reactivity to the cold stimulus with similar pressor responses compared with salt reduction, which may be attributed to the blunted neurovascular transduction-a compensatory mechanism for hemodynamic homeostasis in premenopausal women with a history of normal pregnancy.


Assuntos
Sistema Cardiovascular/inervação , Temperatura Baixa , Dieta Hipossódica , Hemodinâmica , Músculo Esquelético/inervação , Pré-Menopausa , Cloreto de Sódio na Dieta/administração & dosagem , Sistema Nervoso Simpático/fisiologia , Adulto , Pressão Sanguínea , Feminino , Frequência Cardíaca , Humanos , Pessoa de Meia-Idade , Paridade , Gravidez , Distribuição Aleatória , Fatores de Tempo , Vasoconstrição
5.
Am J Physiol Regul Integr Comp Physiol ; 321(2): R260-R270, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34231375

RESUMO

Previous studies have demonstrated that sympathetic baroreflex sensitivity (BRS) increases during orthostatic stress in humans. We recently showed that dietary salt intake affects sympathetic neural control in healthy premenopausal women. This study aimed to determine whether salt loading versus salt reduction would impact sympathetic BRS during orthostasis in premenopausal women with a history of normal pregnancy. Nine healthy women [42 ± 3 (SD) yr] were given a standardized isocaloric high-salt (250 mEq sodium/day) or low-salt (50 mEq sodium/day) diet for 1 wk each (∼2 mo apart with the order randomized), whereas water intake was ad libitum. Laboratory testing was performed following each high- and low-salt period in the midluteal phase of the menstrual cycle. Hemodynamics and muscle sympathetic nerve activity (MSNA) were measured at baseline (supine; 2 min) and during a graded head-up tilt (30° for 5 min and 60° for 20 min). Sympathetic BRS was assessed during baseline and head-up tilt. Hemodynamics were not different between salt conditions during baseline or tilt. Both supine and upright MSNA indices were lower in high salt than low salt (all P < 0.05), however, there was no interaction effect (P = 0.507-0.996). On moving from supine to upright, sympathetic BRS remained unchanged in high salt but increased in low salt (P = 0.028 for interaction). Thus, salt loading diminishes the responsiveness of sympathetic BRS during orthostasis compared with salt reduction in healthy premenopausal women with prior normal pregnancy. Whether this is one underlying mechanism for salt-induced development of hypertension during ambulation remains to be determined.


Assuntos
Barorreflexo , Dieta Hipossódica , Tontura/fisiopatologia , Hemodinâmica , Músculo Esquelético/inervação , Cloreto de Sódio na Dieta/efeitos adversos , Sistema Nervoso Simpático/fisiopatologia , Adulto , Pressão Sanguínea , Estudos Cross-Over , Tontura/diagnóstico , Feminino , Frequência Cardíaca , Humanos , Pessoa de Meia-Idade , Gravidez , Distribuição Aleatória , Texas , Teste da Mesa Inclinada , Fatores de Tempo
6.
Am J Physiol Heart Circ Physiol ; 319(3): H571-H581, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32734815

RESUMO

Salt intake may alter blood pressure (BP) regulation, but no study has investigated the impact of salt reduction versus salt loading on morning blood pressure surge (MBPS) and sympathetic neural control in premenopausal women with a history of normal pregnancy. Nine healthy women (42 ± 3 yr; mean ± SD) were given a low-salt diet (LS; 50 mEq sodium/day) and high-salt diet (HS; 250 mEq sodium/day) for 1 wk each (~2 mo apart with the order randomized), while water intake was ad libitum. Ambulatory BP at 24 h was measured, and the percent change in blood volume (BV) was calculated following LS and HS. MBPS was defined as the morning systolic BP (averaged for 2 h after wake-up) minus the lowest nocturnal systolic BP. Beat-by-beat BP, heart rate, and muscle sympathetic nerve activity (MSNA) were measured during supine rest. Signal averaging was used to characterize changes in beat-by-beat mean arterial pressure and total vascular conductance following spontaneous MSNA bursts to assess sympathetic vascular transduction. Ambulatory BP and MBPS (32 ± 7 vs. 26 ± 12 mmHg, P = 0.208) did not differ between LS and HS. From LS to HS, BV increased by 4.3 ± 3.7% (P = 0.008). MSNA (30 ± 20 vs. 18 ± 13 bursts/100 heartbeats, P = 0.005) was higher, whereas sympathetic vascular transduction was lower in LS than HS (both, P < 0.01). Changes in MSNA from LS to HS were correlated to percent changes in BV (r = -0.673; P = 0.047). Thus, salt intake affects sympathetic neural control but not MBPS in premenopausal women with a history of normal pregnancy. The underlying mechanisms remain unknown; however, alterations in sympathetic vascular transduction may, in part, contribute.NEW & NOTEWORTHY This is the first study to demonstrate that MBPS and ambulatory BP were not affected by salt intake despite a significant change in sympathetic outflow in healthy premenopausal women with a history of normal pregnancy. This may be due to compensatory adaptations in MSNA and sympathetic vascular transduction during salt reduction versus salt loading.


Assuntos
Pressão Sanguínea , Sistema Cardiovascular/inervação , Ritmo Circadiano , Dieta Hipossódica , Músculo Esquelético/inervação , Cloreto de Sódio na Dieta/administração & dosagem , Sistema Nervoso Simpático/fisiologia , Adaptação Fisiológica , Adulto , Estudos Cross-Over , Feminino , Frequência Cardíaca , Humanos , Pessoa de Meia-Idade , Paridade , Gravidez , Pré-Menopausa , Estudos Prospectivos , Distribuição Aleatória , Fatores de Tempo
7.
Artigo em Inglês | MEDLINE | ID: mdl-28223393

RESUMO

The novel bacterial topoisomerase inhibitor class is an investigational type of antibacterial inhibitor of DNA gyrase and topoisomerase IV that does not have cross-resistance with the quinolones. Here, we report the evaluation of the in vitro properties of a new series of this type of small molecule. Exemplar compounds selectively and potently inhibited the catalytic activities of Escherichia coli DNA gyrase and topoisomerase IV but did not block the DNA breakage-reunion step. Compounds showed broad-spectrum inhibitory activity against a wide range of Gram-positive and Gram-negative pathogens, including biodefence microorganisms and Mycobacterium tuberculosis No cross-resistance with fluoroquinolone-resistant Staphylococcus aureus and E. coli isolates was observed. Measured MIC90 values were 4 and 8 µg/ml against a panel of contemporary multidrug-resistant isolates of Acinetobacter baumannii and E. coli, respectively. In addition, representative compounds exhibited greater antibacterial potency than the quinolones against obligate anaerobic species. Spontaneous mutation rates were low, with frequencies of resistance typically <10-8 against E. coli and A. baumannii at concentrations equivalent to 4-fold the MIC. Compound-resistant E. coli mutants that were isolated following serial passage were characterized by whole-genome sequencing and carried a single Arg38Leu amino acid substitution in the GyrA subunit of DNA gyrase. Preliminary in vitro safety data indicate that the series shows a promising therapeutic index and potential for low human ether-a-go-go-related gene (hERG) inhibition (50% inhibitory concentration [IC50], >100 µM). In summary, the compounds' distinct mechanism of action relative to the fluoroquinolones, whole-cell potency, low potential for resistance development, and favorable in vitro safety profile warrant their continued investigation as potential broad-spectrum antibacterial agents.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , DNA Topoisomerase IV/antagonistas & inibidores , Escherichia coli/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Inibidores da Topoisomerase II/farmacologia , Ciprofloxacina/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana
8.
Am J Physiol Regul Integr Comp Physiol ; 313(4): R400-R409, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28724547

RESUMO

Arterial stiffness and cardiac function are important predictors of cardiovascular events in patients with hypertension, even with adequate blood pressure (BP) control. We evaluated whether a direct renin inhibitor, aliskiren, reduces arterial stiffness and modulates left ventricular function compared with a diuretic, hydrochlorothiazide, in elderly hypertensive patients. Twenty-one hypertensive patients [67 ± 14 (SD) yr] were randomly assigned to receive 6-mo aliskiren (n = 11) or hydrochlorothiazide (n = 10)-based therapy. We assessed ß-stiffness of the local arteries, arterial elastance (Ea), and echocardiographic variables, including early (E) and late (A) mitral inflow velocity, deceleration time of E, early (E') and late (A') diastolic mitral annular velocity, and left ventricular end-systolic elastance (Ees) before and after treatment. BP decreased similarly (P < 0.001) after both therapies. ß-Stiffness of the carotid artery decreased after aliskiren but increased after hydrochlorothiazide treatment (aliskiren: 6.42 ± 2.34 pre vs. 5.07 ± 1.29 post; hydrochlorothiazide: 5.05 ± 1.78 vs. 7.25 ± 2.68, P = 0.001 for interaction). ß-Stiffness of the femoral and radial arteries were not different after either treatment. Different from aliskiren, E decreased (73 ± 16 vs. 67 ± 14 cm/s, P = 0.026), and the deceleration time was prolonged (218 ± 40 vs. 236 ± 35 ms, P = 0.032) after hydrochlorothiazide therapy, whereas the E/A, and E' remained unchanged after both treatments. Ea and Ees decreased after aliskiren therapy (both P < 0.05), whereas the Ea/Ees (ventricular-arterial coupling) was maintained after both treatments. Thus, aliskiren decreased the stiffness of carotid artery and left ventricular end-systolic elastance with maintenance of ventricular-arterial coupling without any effects on diastolic filling, while hydrochlorothiazide increased carotid arterial stiffness and slowed early diastolic filling in elderly hypertensive patients.


Assuntos
Amidas/farmacologia , Diástole/efeitos dos fármacos , Fumaratos/farmacologia , Hidroclorotiazida/farmacologia , Hipertensão/tratamento farmacológico , Renina/antagonistas & inibidores , Inibidores de Simportadores de Cloreto de Sódio/farmacologia , Rigidez Vascular/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Amidas/uso terapêutico , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Diástole/fisiologia , Ecocardiografia , Feminino , Artéria Femoral/efeitos dos fármacos , Artéria Femoral/fisiopatologia , Fumaratos/uso terapêutico , Humanos , Hidroclorotiazida/uso terapêutico , Hipertensão/diagnóstico por imagem , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Artéria Radial/efeitos dos fármacos , Artéria Radial/fisiopatologia , Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico , Resultado do Tratamento , Rigidez Vascular/fisiologia , Função Ventricular Esquerda/fisiologia
9.
Antimicrob Agents Chemother ; 60(9): 5592-4, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27324777

RESUMO

There is an urgent need for new antibiotics to treat multidrug-resistant Neisseria gonorrhoeae In this report, the microbiology, in vivo pharmacokinetics, and efficacy of REDX05931, a representative novel tricyclic topoisomerase inhibitor, were evaluated. REDX05931 demonstrated high oral bioavailability in mice and reduced N. gonorrhoeae infection after a single dose in a mouse model of gonorrhea. These data support the potential of this series of small molecules as a new treatment for drug-resistant gonorrheal infections.


Assuntos
Antibacterianos/farmacologia , Gonorreia/tratamento farmacológico , Neisseria gonorrhoeae/efeitos dos fármacos , Inibidores da Topoisomerase/farmacologia , Animais , Modelos Animais de Doenças , Gonorreia/microbiologia , Camundongos , Testes de Sensibilidade Microbiana
10.
J Antimicrob Chemother ; 71(7): 1905-13, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27032669

RESUMO

OBJECTIVES: The objective of this study was to characterize the in vitro and in vivo biological properties of a novel series of small-molecule bacterial type IIA topoisomerase inhibitors. METHODS: Bacterial susceptibility testing was performed by broth microdilution. Resistance frequencies were determined by plating bacteria onto agar containing test compound and enumerating mutants. Bacteria were passaged using subinhibitory concentrations of antibacterials to generate resistance. Target enzyme inhibition was determined by exposure to antibacterials and DNA; topoisomers were visualized by gel electrophoresis. Oral and intravenous pharmacokinetic profiles were determined in mice. In vivo efficacy was determined using a mouse model of septicaemia and thigh infection with MSSA and MRSA, respectively. RESULTS: Representative compounds REDX04139, REDX05604 and REDX05931 demonstrated in vitro potency against a range of Gram-positive and fastidious Gram-negative pathogens. Clinical isolate testing revealed REDX04139 and REDX05931 had MIC90 values of 0.25 and 0.5 mg/L, respectively, for MRSA and MIC90 values of 2 mg/L for streptococci. REDX04139 was bactericidal in vitro against Staphylococcus aureus at 8× MIC over 6 h. Pharmacokinetic profiling of REDX04139 and REDX05604 in mice revealed low clearance and excellent bioavailability (≥71%). REDX04139 provided 100% survival against S. aureus in a mouse septicaemia model, while REDX05604 reduced bacterial load by up to 3.7 log units in the MRSA mouse thigh infection model. CONCLUSIONS: Redx Pharma has discovered a novel series of topoisomerase inhibitors that are being further developed for drug-resistant bacteria.


Assuntos
Antibacterianos/farmacologia , DNA Girase/metabolismo , DNA Topoisomerase IV/antagonistas & inibidores , Hidrocarbonetos Cíclicos/farmacologia , Staphylococcus/efeitos dos fármacos , Animais , Antibacterianos/isolamento & purificação , Antibacterianos/farmacocinética , Disponibilidade Biológica , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Células Hep G2 , Humanos , Hidrocarbonetos Cíclicos/isolamento & purificação , Hidrocarbonetos Cíclicos/farmacocinética , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Sepse/tratamento farmacológico , Sepse/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Streptococcus/efeitos dos fármacos , Análise de Sobrevida
11.
Bioorg Med Chem Lett ; 26(17): 4179-83, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27499455

RESUMO

There is an urgent and unmet medical need for new antibacterial drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. During the course of our wider efforts to discover and exploit novel mechanism of action antibacterials, we have identified a novel series of isothiazolone based inhibitors of bacterial type II topoisomerase. Compounds from the class displayed excellent activity against both Gram-positive and Gram-negative bacteria with encouraging activity against a panel of MDR clinical Escherichia coli isolates when compared to ciprofloxacin. Representative compounds also displayed a promising in vitro safety profile.


Assuntos
Antibacterianos/química , DNA Topoisomerases Tipo II/metabolismo , Tiazóis/química , Tiazolidinas/química , Inibidores da Topoisomerase II/química , Antibacterianos/síntese química , Antibacterianos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , DNA Topoisomerases Tipo II/química , Avaliação Pré-Clínica de Medicamentos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Células Hep G2 , Humanos , Testes de Sensibilidade Microbiana , Mutação , Relação Estrutura-Atividade , Tiazóis/síntese química , Tiazóis/farmacologia , Tiazolidinas/síntese química , Tiazolidinas/farmacologia , Inibidores da Topoisomerase II/síntese química , Inibidores da Topoisomerase II/farmacologia
12.
Clin Auton Res ; 26(6): 395-405, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27506589

RESUMO

PURPOSE: Women with a history of hypertensive pregnancy are at greater risk for future cardiovascular events; however, the mechanisms for this increased risk are unknown. Evidence suggests that an exercise stimulus unmasks latent hypertensive tendencies, identifying individuals at the greatest risk for developing cardiovascular disease. The current study examined the hypothesis that women with a hypertensive pregnancy history exhibit an augmented exercise pressor response. METHODS: Normotensive women with a history of healthy pregnancy (CON; n = 9) and hypertensive pregnancy (HP+; n = 12) were studied during the mid-luteal phase of the menstrual cycle. Heart rate (HR), systolic and diastolic blood pressure (SBP, DBP), and muscle sympathetic nerve activity (MSNA) were measured during a cold pressor test (CPT), and, following a sufficient period of recovery, during static handgrip to fatigue (SHG) and post-exercise circulatory arrest (PECA). RESULTS: The BP, HR, and MSNA responses to the CPT were similar between groups. The SBP response to SHG and PECA was similar between groups, but DBP and HR were significantly greater in HP+ women (both p < 0.05). MSNA burst frequency, but not burst incidence or total activity, tended to be elevated in HP+ women during the stressor (peak Δ from baseline 31 ± 13 vs. 23 ± 13 bursts/min; p for group = 0.06). CONCLUSION: Despite no clinical signs of cardiovascular disease or hypertension, women with a history of hypertensive pregnancy display an enhanced cardiovascular reactivity to an exercise stimulus compared to women with a healthy pregnancy history. This response may be indicative of impaired cardiovascular control that precedes the clinical manifestation of hypertension or cardiovascular events.


Assuntos
Sistema Cardiovascular/fisiopatologia , Exercício Físico , Força da Mão , Hipertensão Induzida pela Gravidez/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Adulto , Pressão Sanguínea , Temperatura Baixa , Feminino , Frequência Cardíaca , Humanos , Fadiga Muscular , Músculo Esquelético/inervação , Músculo Esquelético/fisiopatologia , Pré-Eclâmpsia/fisiopatologia , Gravidez
13.
BMC Public Health ; 16(1): 1148, 2016 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-27829449

RESUMO

BACKGROUND: Physical activity is recommended for people with peripheral arterial disease (PAD), and can improve walking capacity and quality of life; and reduce pain, requirement for surgery and cardiovascular events. This trial will assess the efficacy of a brief behavioral counselling intervention delivered by allied health professionals to improve physical activity in people with PAD. METHODS: This is a multi-center randomised controlled trial in four cities across Australia. Participants (N = 200) will be recruited from specialist vascular clinics, general practitioners and research databases and randomised to either the control or intervention group. Both groups will receive usual medical care, a written PAD management information sheet including advice to walk, and four individualised contacts from a protocol-trained allied health professional over 3 months (weeks 1, 2, 6, 12). The control group will receive four 15-min telephone calls with general discussion about PAD symptoms and health and wellbeing. The intervention group will receive behavioral counselling via two 1-h face-to-face sessions and two 15-min telephone calls. The counselling is based on the 5A framework and will promote interval walking for 3 × 40 min/week. Assessments will be conducted at baseline, and 4, 12 and 24 months by staff blinded to participant allocation. Objectively assessed outcomes include physical activity (primary), sedentary behavior, lower limb body function, walking capacity, cardiorespiratory fitness, event-based claudication index, vascular interventions, clinical events, cardiovascular function, circulating markers, and anthropometric measures. Self-reported outcomes include physical activity and sedentary behavior, walking ability, pain severity, and health-related quality of life. Data will be analysed using an intention-to-treat approach. An economic evaluation will assess whether embedding the intervention into routine care would likely be value for money. A cost-effectiveness analysis will estimate change in cost per change in activity indicators due to the intervention, and a cost-utility analysis will assess change in cost per quality-adjusted life year. A full uncertainty analysis will be undertaken, including a value of information analysis, to evaluate the economic case for further research. DISCUSSION: This trial will evaluate the efficacy and cost-effectiveness of a brief behavioral counselling intervention for a common cardiovascular disease with significant burden. TRIAL REGISTRATION: ACTRN 12614000592640 Australian New Zealand Clinical Trials Registry. Registration Date 4 June 2014.


Assuntos
Pessoal Técnico de Saúde , Terapia Comportamental/métodos , Aconselhamento/métodos , Exercício Físico/psicologia , Doença Arterial Periférica/terapia , Adulto , Austrália , Terapia Comportamental/economia , Protocolos Clínicos , Análise Custo-Benefício , Aconselhamento/economia , Feminino , Humanos , Masculino , Nova Zelândia , Doença Arterial Periférica/psicologia , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Resultado do Tratamento , Caminhada/psicologia
14.
J Physiol ; 593(5): 1159-68, 2015 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-25545472

RESUMO

Asians have a lower prevalence of hypertensive disorders of pregnancy than Caucasians. Since sympathetic overactivity and dysregulation of the renal-adrenal system (e.g. low aldosterone levels) have been found in preeclamptic women, we hypothesized that Asians have lower muscle sympathetic nerve activity (MSNA) and greater aldosterone concentrations during normal pregnancy than Caucasians. In a prospective study, blood pressure (BP), heart rate (HR), and MSNA were measured during supine and upright tilt (30 deg and 60 deg for 5 min each) in 9 Asians (32 ± 1 years (mean ± SEM)) and 12 Caucasians (29 ± 1 years) during pre-, early (≤8 weeks of gestation) and late (32-36 weeks) pregnancy, and post-partum (6-10 weeks after delivery). Supine MSNA increased with pregnancy in both groups (P < 0.001); it was significantly lower in Asians than Caucasians (14 ± 3 vs. 23 ± 3 bursts min(-1) and 16 ± 5 vs. 30 ± 3 bursts min(-1) in early and late pregnancy, respectively; P = 0.023). BP decreased during early pregnancy (P < 0.001), but was restored during late pregnancy. HR increased during pregnancy (P < 0.001) with no racial difference (P = 0.758). MSNA increased during tilting and it was markedly lower in Asians than Caucasians in late pregnancy (31 ± 6 vs. 49 ± 3 bursts min(-1) at 60 deg tilt; P = 0.003). Upright BP was lower in Asians, even in pre-pregnancy (P = 0.006), and this racial difference persisted during pregnancy. Direct renin and aldosterone increased during pregnancy (both P < 0.001); these hormones were greater in Asians (P = 0.086 and P = 0.014). Thus, Asians have less sympathetic activation but more upregulated renal-adrenal responses than Caucasians during pregnancy. These results may explain, at least in part, why Asian women are at low risk of hypertensive disorders in pregnancy.


Assuntos
Aldosterona/sangue , Hipertensão Induzida pela Gravidez/etnologia , Gravidez/fisiologia , Renina/sangue , Sistema Nervoso Simpático/fisiologia , Glândulas Suprarrenais/fisiologia , Adulto , Povo Asiático , Pressão Sanguínea , Feminino , Frequência Cardíaca , Humanos , Rim/fisiologia , Gravidez/sangue , Gravidez/etnologia , População Branca
15.
Exp Physiol ; 99(6): 839-48, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24443350

RESUMO

We compared the effect of age- and sex-related differences in haemodynamics, blood volume (BV) and left ventricular (LV) size and mass on resting muscle sympathetic nerve activity (MSNA) in healthy, normotensive adults. Twenty young men (19-47 years old) and 20 young women (21-46 years old) as well as 15 older men (62-80 years old) and 15 older women (60-82 years old) were studied. Cardiac output (acetylene rebreathing), total peripheral resistance, forearm vascular resistance (FVR; venous occlusion plethysmography) and MSNA were measured during supine rest. Blood volume was calculated (CO rebreathing), and LV mass, end-diastolic (LVEDV) and end-systolic volumes (LVESV) were measured using magnetic resonance imaging. Cardiac index (P < 0.001 and P = 0.016), BV (both P < 0.001), LV mass (P < 0.001 and P = 0.002), LVEDV (P < 0.001 and P = 0.002) and LVESV (both P < 0.001) were lower in the older and female groups, respectively. Total peripheral resistance was significantly higher in the older (P < 0.001) and female groups (P = 0.014), but FVR was increased in the female groups (P = 0.048) only (age, P = 0.089). The MSNA was greater in the older groups (P < 0.001) only (sex, P = 0.228). Increased MSNA was shown to correlate with a decrease in BV (P = 0.004) in men only when adjusted for age (women, P = 0.133). There was a positive relation between MSNA and FVR (P = 0.020) in men but not women (P = 0.422). There were no significant relations between MSNA and LV mass, LVEDV or LVESV. The findings suggest that the increase in resting MSNA with age may be related to the decline in BV in men only, but it is unknown whether sex differences in sympathetic adrenergic vasoconstriction occur independently of these changes.


Assuntos
Fibras Adrenérgicas/fisiologia , Envelhecimento/fisiologia , Volume Sanguíneo/fisiologia , Ventrículos do Coração/anatomia & histologia , Hemodinâmica/fisiologia , Caracteres Sexuais , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/fisiologia , Débito Cardíaco/fisiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Nervo Fibular/fisiologia , Adulto Jovem
16.
Amino Acids ; 46(6): 1491-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24633453

RESUMO

We investigated the effect of exercise in the heat on both intracellular and extracellular Hsp72 in athletes with a prior history of exertional heat illness (EHI). Two groups of runners, one consisting of athletes who had a previous history of EHI, and a control group (CON) of similar age (29.7 ± 1.2 and 29.1 ± 2 years CON vs. EHI) and fitness [maximal oxygen consumption [Formula: see text] 65.7 ± 2 and 64.5 ± 3 ml kg(-1) min(-1) CON vs. EHI] were recruited. Seven subjects in each group ran on a treadmill for 1 h at 72 % [Formula: see text] in warm conditions (30 °C, 40 % RH) reaching rectal temperatures of ~39.3 (CON) and ~39.2 °C (EHI). Blood was collected every 10 min during exercise and plasma was analysed for extracellular Hsp72. Intracellular Hsp72 levels were measured in both monocytes and lymphocytes before and immediately after the 60-min run, and then after 1 h recovery at an ambient temperature of 24 °C. Plasma Hsp72 increased from 1.18 ± 0.14 and 0.86 ± 0.08 ng/ml (CON vs. EHI) at rest to 4.56 ± 0.63 and 4.04 ± 0.45 ng/ml (CON vs. EHI, respectively) at the end of exercise (p < 0.001), with no difference between groups. Lymphocyte Hsp72 was lower in the EHI group at 60 min of exercise (p < 0.05), while monocyte Hsp72 was not different between groups. The results of the present study suggest that the plasma Hsp72 response to exercise in athletes with a prior history of EHI remained similar to that of the CON group, while the lymphocyte Hsp72 response was reduced.


Assuntos
Exercício Físico/fisiologia , Proteínas de Choque Térmico HSP72/sangue , Golpe de Calor/fisiopatologia , Linfócitos/metabolismo , Adulto , Teste de Esforço , Golpe de Calor/sangue , Temperatura Alta , Humanos , Masculino , Monócitos/metabolismo , Consumo de Oxigênio , Corrida
17.
J Strength Cond Res ; 28(3): 767-73, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23897024

RESUMO

Military manual handling requirements range from discrete lifts to continuous and repetitive lifting tasks. For the military to introduce a discrete lifting assessment, the assessment must be predictive of the various submaximum lifting tasks personnel are required to perform. This study investigated the relationship between discrete and repetitive military lifting to assess the validity of implementing a discrete lifting test. Twenty-one soldiers from the Australian Army completed a whole-body box-lifting assessment as a one repetition maximum (1RM) and a series of submaximal lifting repetitions (% 1RM). Performance was measured between the number of lifting repetitions that could be performed at different intensities between 58 and 95% 1RM. A strong curvilinear relationship existed across the entire submaximal lifting range (r = 0.72, p ≤ 0.05). The model developed demonstrated a low predictive error (standard error of the estimate = 7.2% 1RM) with no differences detected in the relationship when comparing individuals of high and low strength. Findings support the use of a discrete functional lifting assessment in providing coverage of a broad range of military lifting tasks. Parallels can be drawn between the trend reported in the current study and weight-training exercises reported in the literature.


Assuntos
Teste de Esforço , Remoção , Militares , Força Muscular/fisiologia , Resistência Física/fisiologia , Análise e Desempenho de Tarefas , Adolescente , Adulto , Austrália , Humanos , Masculino , Músculo Esquelético/fisiologia , Valor Preditivo dos Testes , Levantamento de Peso/fisiologia , Avaliação da Capacidade de Trabalho , Adulto Jovem
18.
Artigo em Inglês | MEDLINE | ID: mdl-38980809

RESUMO

Purpose: The purpose of this pilot study was to investigate cannabidiol (CBD) cream's effects on muscle soreness and performance after exercise. Materials and Methods: This double-blinded, placebo-controlled experiment included 15 men and 13 women (n = 28; mean ± standard deviation age: 23.29 ± 2.54 years) untrained in lower-body resistance training. Participants were randomized into control (NG, n = 9), CBD (CG, n = 9), or placebo (PG, n = 10) groups. Participants completed a lower-body fatigue protocol (FP) consisting of unilateral maximal concentric and eccentric isokinetic muscle actions of the quadriceps and hamstrings (5 sets, 10 repetitions, both legs). CG and PG participants applied ∼100 mg CBD or placebo cream, respectively, matched for weight and appearance to the quadriceps on three separate days. NG participants engaged in a sitting rest period matched in duration to cream application processes. Questionnaires, pressure-pain threshold (PPT), peak torque test (PTT), and countermovement jump (CMJ) were assessed. Mixed-model analysis of variance was conducted to assess main effects and interactions (group × muscle × time; group × time). Results: There were no significant interactions or main effects for group for PPT, CMJ, or PTT. There were main effects for time (p < 0.05) for all soreness questions, PPT, CMJ, and PTT. There was one significant interaction (group × time; p = 0.045) for cream/rest effect questions, in which PG participants perceived the effect of cream to be greater than the effect of rest for NG participants. There were main effects for group (p ≤ 0.031) for all soreness questions, in which PG participants perceived enhanced recovery. Conclusions: The present pilot study did not discover any significant impacts of CBD cream use for muscle recovery. For individuals seeking to attenuate muscle soreness and improve performance, the current dose of this topical CBD product may not be an effective treatment.

19.
J Physiol ; 591(23): 5913-22, 2013 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-24060993

RESUMO

Cardiovascular risk remains high in patients with hypertension even with adequate blood pressure (BP) control. One possible mechanism may be sympathetic activation via the baroreflex. We tested the hypothesis that chronic inhibition of renin reduces BP without sympathetic activation, but diuresis augments sympathetic activity in elderly hypertensives. Fourteen patients with stage-I hypertension (66 ± 5 (SD) years) were treated with a direct renin inhibitor, aliskiren (n = 7), or a diuretic, hydrochlorothiazide (n = 7), for 6 months. Muscle sympathetic nerve activity (MSNA), BP, direct renin and aldosterone were measured during supine and a graded head-up tilt (HUT; 5 min 30° and 20 min 60°), before and after treatment. Sympathetic baroreflex sensitivity (BRS) was assessed. Both groups had similar BP reductions after treatment (all P < 0.01), while MSNA responses were different between hydrochlorothiazide and aliskiren (P = 0.006 pre/post × drug). Both supine and upright MSNA became greater after hydrochlorothiazide treatment (supine, 72 ± 18 post vs. 64 ± 15 bursts (100 beats)(-1) pre; 60° HUT, 83 ± 10 vs. 78 ± 13 bursts (100 beats)(-1); P = 0.002). After aliskiren treatment, supine MSNA remained unchanged (69 ± 13 vs. 64 ± 8 bursts (100 beats)(-1)), but upright MSNA was lower (74 ± 15 vs. 85 ± 10 bursts (100 beats)(-1); P = 0.012 for pre/post × posture). Direct renin was greater after both treatments (both P < 0.05), while upright aldosterone was greater after hydrochlorothiazide only (P = 0.002). The change in upright MSNA by the treatment was correlated with the change of aldosterone (r = 0.74, P = 0.002). Upright sympathetic BRS remained unchanged after either treatment. Thus, chronic renin inhibition may reduce upright MSNA through suppressed renin activity, while diuresis may evoke sympathetic activation via the upregulated renin-angiotensin-aldosterone system, without changing intrinsic sympathetic baroreflex function in elderly hypertensive patients.


Assuntos
Amidas/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Fumaratos/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Renina/antagonistas & inibidores , Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico , Sistema Nervoso Simpático/efeitos dos fármacos , Idoso , Pressão Sanguínea/efeitos dos fármacos , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Músculos/fisiologia , Nervo Fibular/fisiologia , Postura/fisiologia , Sistema Nervoso Simpático/fisiologia
20.
J Strength Cond Res ; 26 Suppl 2: S23-9, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22643137

RESUMO

Psychophysical assessments, such as the maximum acceptable lift, have been used to establish worker capability and set safe load limits for manual handling tasks in occupational settings. However, in military settings, in which task demand is set and capable workers must be selected, subjective measurements are inadequate, and maximal capacity testing must be used to assess lifting capability. The aim of this study was to establish and compare the relationship between maximal lifting capacity and a self-determined tolerable lifting limit, maximum acceptable lift, across a range of military-relevant lifting tasks. Seventy male soldiers (age 23.7 ± 6.1 years) from the Australian Army performed 7 strength-based lifting tasks to determine their maximum lifting capacity and maximum acceptable lift. Comparisons were performed to identify maximum acceptable lift relative to maximum lifting capacity for each individual task. Linear regression was used to identify the relationship across all tasks when the data were pooled. Strong correlations existed between all 7 lifting tasks (rrange = 0.87-0.96, p < 0.05). No differences were found in maximum acceptable lift relative to maximum lifting capacity across all tasks (p = 0.46). When data were pooled, maximum acceptable lift was equal to 84 ± 8% of the maximum lifting capacity. This study is the first to illustrate the strong and consistent relationship between maximum lifting capacity and maximum acceptable lift for multiple single lifting tasks. The relationship developed between these indices may be used to help assess self-selected manual handling capability through occupationally relevant maximal performance tests.


Assuntos
Remoção , Militares , Força Muscular/fisiologia , Adolescente , Adulto , Austrália , Humanos , Masculino , Músculo Esquelético/fisiologia , Análise e Desempenho de Tarefas , Adulto Jovem
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