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1.
Int J Audiol ; 62(5): 400-409, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-35436167

RESUMO

OBJECTIVE: To assess the benefits of the Ida Institute's Why improve my hearing? Telecare Tool used before the initial hearing assessment appointment. DESIGN: A prospective, single-blind randomised clinical trial with two arms: (i) Why improve my hearing? Telecare Tool intervention, and (ii) standard care control. STUDY SAMPLE: Adults with hearing loss were recruited from two Audiology Services within the United Kingdom's publicly-funded National Health Service. Of 461 individuals assessed for eligibility, 57 were eligible to participate. RESULTS: Measure of Audiologic Rehabilitation Self-efficacy for Hearing Aids (primary outcome) scores did not differ between groups from baseline to post-assessment (Mean change [Δ]= -2.28; 95% confidence interval [CI]= -6.70, 2.15, p= .307) and 10-weeks follow-up (Mean Δ= -2.69; 95% CI= -9.52, 4.15, p = .434). However, Short Form Patient Activation Measure scores significantly improved in the intervention group compared to the control group from baseline to post-assessment (Mean Δ= -6.06, 95% CI= -11.31, -0.82, p = .024, ES= .61) and 10-weeks follow-up (Mean Δ= -9.87, 95% CI= -15.34, -4.40, p = .001, ES= -.97). CONCLUSIONS: This study demonstrates that while a patient-centred telecare intervention completed before management decisions may not improve an individual's self-efficacy to manage their hearing loss, it can lead to improvements in readiness.


Assuntos
Surdez , Perda Auditiva , Adulto , Humanos , Estudos Prospectivos , Método Simples-Cego , Medicina Estatal , Perda Auditiva/reabilitação , Audição , Qualidade de Vida , Análise Custo-Benefício
2.
J Prev Alzheimers Dis ; 6(1): 56-62, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30569087

RESUMO

BACKGROUND: Personalized music programs have been proposed as an adjunct therapy for patients with Alzheimer disease related dementia, and multicenter trials have now demonstrated improvements in agitation, anxiety, and behavioral symptoms. Underlying neurophysiological mechanisms for these effects remain unclear. METHODS: We examined 17 individuals with a clinical diagnosis of Alzheimer disease related dementia using functional MRI following a training period in a personalized music listening program. RESULTS: We find that participants listening to preferred music show specific activation of the supplementary motor area, a region that has been associated with memory for familiar music that is typically spared in early Alzheimer disease. We also find widespread increases in functional connectivity in corticocortical and corticocerebellar networks following presentation of preferred musical stimuli, suggesting a transient effect on brain function. CONCLUSIONS: Findings support a mechanism whereby attentional network activation in the brain's salience network may lead to improvements in brain network synchronization.


Assuntos
Doença de Alzheimer/fisiopatologia , Encéfalo/fisiologia , Cerebelo/fisiologia , Córtex Cerebral/fisiologia , Demência/fisiopatologia , Córtex Motor/fisiologia , Música , Estimulação Acústica , Idoso , Doença de Alzheimer/complicações , Percepção Auditiva/fisiologia , Demência/complicações , Feminino , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/fisiologia
3.
Klin Lab Diagn ; (11): 3-11, 2013 Nov.
Artigo em Russo | MEDLINE | ID: mdl-24640103

RESUMO

The article considers different techniques supporting clinician in evaluation of kidney function and kidneys damage. The actual studies data can assist to determine usefulness of many new markers and to clarify their role in treatment of patients with risk of development of kidneys diseases.


Assuntos
Biomarcadores/sangue , Creatinina/sangue , Nefropatias/sangue , Rim/patologia , Cistatinas/sangue , Humanos , Rim/lesões , Nefropatias/diagnóstico , Nefropatias/patologia
4.
AJNR Am J Neuroradiol ; 32(10): 1963-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21885716

RESUMO

BACKGROUND AND PURPOSE: Deep brain stimulation of the thalamus has become a valuable treatment for medication-refractory essential tremor, but current targeting provides only a limited ability to account for individual anatomic variability. We examined whether functional connectivity measurements among the motor cortex, superior cerebellum, and thalamus would allow discrimination of precise targets useful for image guidance of neurostimulator placement. MATERIALS AND METHODS: Resting BOLD images (8 minutes) were obtained in 58 healthy adolescent and adult volunteers. Regions of interest were identified from an anatomic atlas and a finger movement task in each subject in the primary motor cortex and motor activation region of the bilateral superior cerebellum. Correlation was measured in the time series of each thalamic voxel with the 4 seeds. An analogous procedure was performed on a single subject imaged for 10 hours to constrain the time needed for single-subject optimization of thalamic targets. RESULTS: Mean connectivity images from 58 subjects showed precisely localized targets within the expected location of the ventral intermediate nucleus of the thalamus, within a single voxel of currently used deep brain stimulation anatomic targets. These targets could be mapped with single-voxel accuracy in a single subject with 3 hours of imaging time, though targets were reproduced in different locations for the individual than for the group averages. CONCLUSIONS: Interindividual variability likely exists in optimal placement for thalamic deep brain stimulation targeting of the cerebellar thalamus for essential tremor. Individualized thalamic targets can be precisely estimated for image guidance with sufficient imaging time.


Assuntos
Mapeamento Encefálico/métodos , Estimulação Encefálica Profunda/métodos , Tremor Essencial/diagnóstico , Tremor Essencial/terapia , Imageamento por Ressonância Magnética/métodos , Radiografia Intervencionista/métodos , Adolescente , Criança , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto Jovem
5.
AJNR Am J Neuroradiol ; 32(3): 548-55, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21273356

RESUMO

BACKGROUND AND PURPOSE: Measurements of resting-state functional connectivity have increasingly been used for characterization of neuropathologic and neurodevelopmental populations. We collected data to characterize how much imaging time is necessary to obtain reproducible quantitative functional connectivity measurements needed for a reliable single-subject diagnostic test. MATERIALS AND METHODS: We obtained 100 five-minute BOLD scans on a single subject, divided into 10 sessions of 10 scans each, with the subject at rest or while watching video clips of cartoons. These data were compared with resting-state BOLD scans from 36 healthy control subjects by evaluating the correlation between each pair of 64 small spheric regions of interest obtained from a published functional brain parcellation. RESULTS: Single-subject and group data converged to reliable estimates of individual and population connectivity values proportional to 1 / sqrt(n). Dramatic improvements in reliability were seen by using ≤25 minutes of imaging time, with smaller improvements for additional time. Functional connectivity "fingerprints" for the individual and population began diverging at approximately 15 minutes of imaging time, with increasing reliability even at 4 hours of imaging time. Twenty-five minutes of BOLD imaging time was required before any individual connections could reliably discriminate an individual from a group of healthy control subjects. A classifier discriminating scans during which our subject was resting or watching cartoons was 95% accurate at 10 minutes and 100% accurate at 15 minutes of imaging time. CONCLUSIONS: An individual subject and control population converged to reliable different functional connectivity profiles that were task-modulated and could be discriminated with sufficient imaging time.


Assuntos
Encéfalo/fisiologia , Potenciais Evocados Visuais/fisiologia , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/fisiologia , Percepção Visual/fisiologia , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
6.
Colloids Surf B Biointerfaces ; 67(1): 32-40, 2008 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-18815013

RESUMO

Bacterial biofilms were imaged by atomic force microscopy (AFM), and their elasticity and adhesion to the AFM tip were determined from a series of tip extension and retraction cycles. Though the five bacterial strains studied included both Gram-negative and -positive bacteria and both environmental and laboratory strains, all formed simple biofilms on glass surfaces. Cellular spring constants, determined from the extension portion of the force cycle, varied between 0.16+/-0.01 and 0.41+/-0.01 N/m, where larger spring constants were measured for Gram-positive cells than for Gram-negative cells. The nonlinear regime in the extension curve depended upon the biomolecules on the cell surface: the extension curves for the smooth Gram-negative bacterial strains with the longest lipopolysaccharides on their surface had a larger nonlinear region than the rough bacterial strain with shorter lipopolysaccharides on the surface. Adhesive forces between the retracting silicon nitride tip and the cells varied between cell types in terms of the force components, the distance components, and the number of adhesion events. The Gram-negative cells' adhesion to the tip showed the longest distance components, sometimes more than 1 microm, whereas the shortest distance adhesion events were measured between the two Gram-positive cell types and the tip. Fixation of free-swimming planktonic cells by NHS and EDC perturbed both the elasticity and the adhesive properties of the cells. Here we consider the biochemical meaning of the measured physical properties of simple biofilms and implications to the colonization of surfaces in the first stages of biofilm formation.


Assuntos
Aderência Bacteriana/fisiologia , Biofilmes , Elasticidade/fisiologia , Microscopia de Força Atômica , Bacillus subtilis/fisiologia , Bacillus subtilis/ultraestrutura , Escherichia coli/fisiologia , Escherichia coli/ultraestrutura , Micrococcus luteus/fisiologia , Micrococcus luteus/ultraestrutura , Pseudomonas putida/fisiologia , Pseudomonas putida/ultraestrutura
7.
Scand J Clin Lab Invest ; 66(4): 351-5, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16777763

RESUMO

The effects of a lower-extremity progressive resistance-training program (PRT) on risk factors for coronary artery disease (CAD) were determined in patients with multiple sclerosis (MS). Twelve ambulatory women with MS (47.3+/-4.7 years; Expanded Disability Status Score (EDSS), 4.00+/-1.37) completed twice weekly lower-body PRT for 8 weeks. Knee extensor and ankle flexor strength improved significantly (p<0.05) after training, and self-reported fatigue decreased (p<0.05). Serum triglyceride concentrations decreased (p<0.05) but body-weight and fatness, blood pressure, and serum glucose, total cholesterol and high-density lipoprotein cholesterol were unchanged. However, the number of CAD risk factors that reached the clinical threshold for each subject declined after PRT, suggesting that resistance training can promote CAD risk reduction in ambulatory female MS subjects.


Assuntos
Doença da Artéria Coronariana/prevenção & controle , Exercício Físico/fisiologia , Esclerose Múltipla/complicações , Atividades Cotidianas , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Estatísticas não Paramétricas
8.
J Sports Med Phys Fitness ; 45(3): 419-23, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16230995

RESUMO

AIM: Endothelin-1 (ET-1) is a potent vasoconstricting peptide released mostly from vascular endothelial cells. Isolated exercise sessions of relatively long duration (=or>30 min) have produced increases in plasma ET-1 concentration while shorter exercise sessions usually have not. The purpose of the present study was to verify an effect of exercise duration at a steady work rate on plasma ET-1 concentration. METHODS: Eleven endurance-trained males (age 27+/-6 years; maximal oxygen consumption--VO2max--56+/-7 mLxkg-1xmin-1, body fat 11+/-5%; mean+/-SD) exercised on a treadmill at 70% VO2max on 2 occasions separated by at least 2 weeks. During a short-duration session, subjects expended approximately 3,360 kJ (60+/-2 min). During a long-duration session, subjects expended approximately 6,300 kJ (112+/-4 min). Six of the subjects performed the 3,360 kJ session before the 6,300 kJ session while the other 5 subjects performed the 6,300 kJ session first. RESULTS: The short-duration session did not cause plasma ET-1 concentration to change immediately after exercise (0.23+/-0.01 pmolxL-1 before exercise, 0.22+/-0.02 pmolxL-1 after exercise, mean+/-SE). However, 10 of 11 subjects had increased ET-1 after the long-duration session (0.28+/-0.02 pmolxL-1 before exercise, 0.32+/-0.02 pmolxL-1 after exercise, P=0.0004). A treatment-by-time effect was present (P=0.003). CONCLUSION: These results demonstrate an effect of exercise duration on plasma ET-1 concentration. Exercise duration is, therefore, an essential consideration when investigating exercise's effect on ET-1.


Assuntos
Endotelina-1/sangue , Exercício Físico/fisiologia , Resistência Física/fisiologia , Adulto , Endotélio Vascular/fisiologia , Teste de Esforço , Hidratação , Humanos , Masculino , Consumo de Oxigênio/fisiologia , Estudos Prospectivos , Fatores de Tempo
9.
Int J Sports Med ; 26(8): 669-74, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16158373

RESUMO

Exercise training can improve lipid and lipoprotein concentrations and reduce the risk of heart disease. Little information is available concerning aerobic dance training and lipoprotein concentration changes in women. The purpose of this study was to compare the effects of two different methods of step bench training on cardiorespiratory fitness, body composition, and lipoprotein concentrations in college-aged females. Subjects were assigned to one of three groups: a traditional continuous step (CS), an interval step group (IS), or a non-exercise control group (C). The CS and the IS groups participated in three 50-minute sessions for 12 weeks. The CS session included a warm-up, 30-35 min of continuous bench stepping, 10-15 min of calisthenic exercises, and a 5-min cool-down. The IS sessions included a 5-7-min warm-up, 35-40 min of alternating intervals of bench stepping and non-step aerobic dance, and a 5-7-min cool-down. Target heart rates were maintained within 70 to 85% of maximal heart rate. Results showed increases in HDL-C concentrations in the IS group (p<0.05). Decreases in percent body fat were evident in both dance groups (p<0.05) and cardiovascular fitness increased in both groups (p<0.01). No changes were evident in the control group. In college-aged women, 12 weeks of IS or CS training improved cardiorespiratory fitness and body composition. In addition, IS training appears to have a greater effect on HDL-C concentrations than CS training.


Assuntos
Dança/fisiologia , Exercício Físico/fisiologia , Lipoproteínas/sangue , Triglicerídeos/sangue , Adolescente , Adulto , Composição Corporal/fisiologia , HDL-Colesterol/sangue , Feminino , Humanos , Aptidão Física/fisiologia
10.
J Sports Med Phys Fitness ; 45(4): 501-6, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16446681

RESUMO

AIM: Extensive research has been undertaken in the area of exercise and hydration. Most work has focused on prehydration. Less is known about different fluid intake patterns during exercise and its effect in thermoregulatory variables in hot environments. This study attempted to determine if ingesting fluid either in a single bolus or intermittently during exercise had different results in thermoregulatory parameters and thirst in a hot environment. METHODS: Six moderately trained men and women (n=6, 5 male, 1 female; mean+/-SD: age 28.5+/-2.5 y; weight 74.4+/-3.3 kg, VO2max 45.9+/-3.7 ml.kg.min-1) completed 2 exercise sessions in a randomized, counterbalanced order. Treatment 1 (bolus) consisted of 60 minutes of bicycling at 50% of VO2max in a climatic chamber (dry bulb temperature, 35 degrees C, 45% relative humidity). Subjects consumed 1 000 ml of plain cool (22 degrees C) water immediately before exercise. During treatment 2 (intermittent) the same environmental conditions were present, but subjects consumed 250 ml of water immediately before exercise. During the bicycle ride, subjects consumed 250 ml of cool water at minutes 15, 30, and 45 of exercise for a total trial volume of 1,000 ml. Tympanic ear temperatures, heart rates, rating of perceived exertion (RPE), and thirst scale data were collected immediately before exercise and at minutes 10, 20, 30, 40, 50, and 60 of exercise. RESULTS: No statistical differences were noted in temperature between treatments (P>0.05). Lower heart rates and thirst scores were noted for the bolus treatment at various time points (P<0.05). Little differences were noted between treatments for RPE during exercise. CONCLUSIONS: These results suggest that consumption of water in a single bolus is more beneficial for some aspects of thermoregulatory control and delaying thirst during exercise in the heat. Additional mechanistic studies with larger sample sizes are warranted.


Assuntos
Ciclismo/fisiologia , Regulação da Temperatura Corporal/fisiologia , Ingestão de Líquidos/fisiologia , Exercício Físico/fisiologia , Temperatura Alta/efeitos adversos , Consumo de Oxigênio/fisiologia , Esforço Físico/fisiologia , Adulto , Desidratação/prevenção & controle , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Sede/fisiologia , Fatores de Tempo
11.
Biochem Soc Trans ; 32(Pt 5): 766-8, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15494010

RESUMO

Reactions involving removal and addition of glucose to N-glycans in the ER (endoplasmic reticulum) are performed in higher eukaryotes by glucosidases I and II and the UDP-glucose:glycoprotein glucosyltransferase respectively. Monoglucosylated N-glycan structures have been implicated in glycoprotein folding or ER quality control. Components of the system appear across a range of organisms; however, the precise combination differs between organisms. We have identified putative components of the system in the protozoal organism Trypanosoma brucei by local alignment searching. The function of one of these components, a glucosidase II alpha-subunit homologue, has been confirmed by phenotyping a null mutant, and an ectopic expression cell line. A combination of MS, methylation linkage analysis, exoglycosidase digestion and partial acetolysis have been used to characterize three novel N-glycan structures on the variant surface glycoprotein of the null mutant. On the basis of our results, we propose that two N-glycan precursors are available for transfer to variant surface glycoprotein (variant 221) in the ER of T. brucei; only one of these precursors is glucosylated after transfer.


Assuntos
Glucosidases/química , Polissacarídeos/química , Trypanosoma brucei brucei/enzimologia , Animais , Asparagina/química , Sítios de Ligação , Linhagem Celular , Retículo Endoplasmático/enzimologia , Retículo Endoplasmático/metabolismo , Espectrometria de Massas , Metilação , Modelos Biológicos , Mutação , Fenótipo , Espectrometria de Massas por Ionização por Electrospray
12.
Scand J Clin Lab Invest ; 63(1): 73-9, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12729072

RESUMO

The purpose of this study was to examine the effect of prolonged exercise on plasma lipid and lipoprotein concentrations and to identify caloric time-points where changes occurred. Eleven active male subjects ran on a treadmill at 70% of maximal fitness (VO2max) and expended 6278.7 kilojoules (Kj) energy (1500 kcal). Blood samples were obtained at the 4185.8 Kj (1000 kcal) timepoint during exercise and at each additional 418.6 Kj (100 kcal) expenditure until 6278.7 Kj was expended. After correcting for plasma volume changes, decreases in low-density lipoprotein cholesterol (LDL-C) were observed during exercise at time-points corresponding to 4604.4 and 5441.5 Kj (1100 and 1300 kcal) of energy expenditure, and immediately after exercise. Total cholesterol concentrations decreased significantly at exercise kilojoule expenditures of 4604.4, 5441.5 and 5860.1 (1100, 1300 and 1400 kcal). There were also exercise induced increases in high-density lipoprotein cholesterol (HDL-C) and HDL2-C concentrations immediately after exercise. Although acute lipid and lipoprotein changes are typically reported in the days following exercise, the current data indicate that some lipoprotein concentrations change during acute exercise. Our data suggest that a threshold of exercise may be necessary to change lipoproteins during exercise. Future work should identify potential mechanisms (lipoprotein lipase, cholesterol ester transport protein, LDL uptake) that alter lipoprotein concentrations during prolonged exercise.


Assuntos
HDL-Colesterol/sangue , LDL-Colesterol/sangue , Teste de Esforço , Exercício Físico/fisiologia , Lipoproteínas HDL/sangue , Adulto , Metabolismo Energético/fisiologia , Humanos , Lipoproteínas HDL2 , Masculino
13.
Sports Med ; 31(15): 1033-62, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11735685

RESUMO

Dose-response relationships between exercise training volume and blood lipid changes suggest that exercise can favourably alter blood lipids at low training volumes, although the effects may not be observable until certain exercise thresholds are met. The thresholds established from cross-sectional literature occur at training volumes of 24 to 32 km (15 to 20 miles) per week of brisk walking or jogging and elicit between 1200 to 2200 kcal/wk. This range of weekly energy expenditure is associated with 2 to 3 mg/dl increases in high-density lipoprotein-cholesterol (HDL-C) and triglyceride (TG) reductions of 8 to 20 mg/dl. Evidence from cross-sectional studies indicates that greater changes in HDL-C levels can be expected with additional increases in exercise training volume. HDL-C and TG changes are often observed after training regimens requiring energy expenditures similar to those characterised from cross-sectional data. Training programmes that elicit 1200 to 2200 kcal/wk in exercise are often effective at elevating HDL-C levels from 2 to 8 mg/dl, and lowering TG levels by 5 to 38 mg/dl. Exercise training seldom alters total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C). However, this range of weekly exercise energy expenditure is also associated with TC and LDL-C reductions when they are reported. The frequency and extent to which most of these lipid changes are reported are similar in both genders, with the exception of TG. Thus, for most individuals, the positive effects of regular exercise are exerted on blood lipids at low training volumes and accrue so that noticeable differences frequently occur with weekly energy expenditures of 1200 to 2200 kcal/wk. It appears that weekly exercise caloric expenditures that meet or exceed the higher end of this range are more likely to produce the desired lipid changes. This amount of physical activity, performed at moderate intensities, is reasonable and attainable for most individuals and is within the American College of Sports Medicine's currently recommended range for healthy adults.


Assuntos
Exercício Físico/fisiologia , Lipídeos/sangue , Lipoproteínas/sangue , Resistência Física/fisiologia , Adulto , Composição Corporal , Colesterol/sangue , Estudos Transversais , Metabolismo Energético/fisiologia , Estudos de Avaliação como Assunto , Terapia por Exercício/métodos , Feminino , Humanos , Hipercolesterolemia/terapia , Estilo de Vida , Masculino , Educação Física e Treinamento/métodos , Fatores Sexuais , Fatores de Tempo , Triglicerídeos/sangue
14.
EMBO J ; 20(17): 4923-34, 2001 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-11532956

RESUMO

Inositol acylation is an obligatory step in glycosylphosphatidylinositol (GPI) biosynthesis whereas mature GPI anchors often lack this modification. The GPI anchors of Trypanosoma brucei variant surface glycoproteins (VSGs) undergo rounds of inositol acylation and deacylation during GPI biosynthesis and the deacylation reactions are inhibited by diisopropylfluorophosphate (DFP). Inositol deacylase was affinity labelled with [3H]DFP and purified. Peptide sequencing was used to clone GPIdeAc, which encodes a protein with significant sequence and hydropathy similarity to mammalian acyloxyacyl hydrolase, an enzyme that removes fatty acids from bacterial lipopolysaccharide. Both contain a signal sequence followed by a saposin domain and a GDSL-lipase domain. GPIdeAc(-/-) trypanosomes were viable in vitro and in animals. Affinity-purified HA-tagged GPIdeAc was shown to have inositol deacylase activity. However, total inositol deacylase activity was only reduced in GPIdeAc(-/-) trypanosomes and the VSG GPI anchor was indistinguishable from wild type. These results suggest that there is redundancy in T.brucei inositol deacylase activity and that there is another enzyme whose sequence is not recognizably related to GPIdeAc.


Assuntos
Monoéster Fosfórico Hidrolases/metabolismo , Proteínas de Protozoários , Trypanosoma brucei brucei/enzimologia , Regiões 3' não Traduzidas/química , Regiões 3' não Traduzidas/genética , Regiões 5' não Traduzidas/química , Regiões 5' não Traduzidas/genética , Sequência de Aminoácidos , Animais , Clonagem Molecular , Glicosilfosfatidilinositóis/metabolismo , Humanos , Isoflurofato/farmacocinética , Isoflurofato/farmacologia , Camundongos , Dados de Sequência Molecular , Fragmentos de Peptídeos/química , Monoéster Fosfórico Hidrolases/química , Monoéster Fosfórico Hidrolases/genética , Reação em Cadeia da Polimerase , Coelhos , Ratos , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Trypanosoma brucei brucei/genética , Trypanosoma brucei brucei/isolamento & purificação , Tripanossomíase Africana/sangue , Tripsina
15.
Med Sci Sports Exerc ; 33(9): 1511-6, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11528340

RESUMO

PURPOSE: Most studies that use either a single exercise session, exercise training, or a cross-sectional design have failed to find a relationship between exercise and plasma lipoprotein(a) [Lp(a)] concentrations. However, a few studies investigating the effects of longer and/or more strenuous exercise have shown elevated Lp(a) concentrations, possibly as an acute-phase reactant to muscle damage. Based on the assumption that greater muscle damage would occur with exercise of longer duration, the purpose of the present study was to determine whether exercise of longer duration would increase Lp(a) concentration and creatine kinase (CK) activity more than exercise of shorter duration. METHODS: Ten endurance-trained men (mean +/- SD: age, 27 +/- 6 yr; maximal oxygen consumption [VO(2max)], 57 +/- 7 mL x kg(-1) x min(-1)) completed two separate exercise sessions at 70% VO(2max). One session required 800 kcal of energy expenditure (60 +/- 6 min), and the other required 1500 kcal (112 +/- 12 min). Fasted blood samples were taken immediately before (0-pre), immediately after (0-post), 1 d after (1-post), and 2 d after (2-post) each exercise session. RESULTS: CK activity increased after both exercise sessions (mean +/- SE; 800 kcal: 0-pre 55 +/- 11, 1-post 168 +/- 64 U x L(-1) x min(-1); 1500 kcal: 0-pre 51 +/- 5, 1-post 187 +/- 30, 2-post 123 +/- 19 U x L(-1) x min(-1); P < 0.05). However, median Lp(a) concentrations were not altered by either exercise session (800 kcal: 0-pre 5.0 mg x dL(-1), 0-post 3.2 mg x dL(-1), 1-post 4.0 mg x dL(-1), 2-post 3.4 mg x dL(-1); 1500 kcal: 0-pre 5.8 mg x dL(-1), 0-post 4.3 mg x dL(-1), 1-post 3.2 mg x dL(-1), 2-post 5.3 mg x dL(-1)). In addition, no relationship existed between exercise-induced changes in CK activity and Lp(a) concentration (800 kcal: r = -0.26; 1500 kcal: r = -0.02). CONCLUSION: These results suggest that plasma Lp(a) concentration will not increase in response to minor exercise-induced muscle damage in endurance-trained runners.


Assuntos
Exercício Físico/fisiologia , Lipoproteína(a)/sangue , Músculo Esquelético/patologia , Resistência Física/fisiologia , Adulto , Creatina Quinase/análise , Creatina Quinase/metabolismo , Estudos Transversais , Humanos , Masculino , Músculo Esquelético/enzimologia , Consumo de Oxigênio , Fatores de Tempo
16.
J Mol Biol ; 309(1): 181-92, 2001 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-11491287

RESUMO

Acyl-CoA binding protein (ACBP) maintains a pool of fatty acyl-CoA molecules in the cell and plays a role in fatty acid metabolism. The biochemical properties of Plasmodium falciparum ACBP are described together with the 2.0 A resolution crystal structures of a P. falciparum ACBP-acyl-CoA complex and of bovine ACBP in two crystal forms. Overall, the bovine ACBP crystal structures are similar to the NMR structures published previously; however, the bovine and parasite ACBP structures are less similar. The parasite ACBP is shown to have a different ligand-binding pocket, leading to an acyl-CoA binding specificity different from that of bovine ACBP. Several non-conservative differences in residues that interact with the ligand were identified between the mammalian and parasite ACBPs. These, together with measured binding-specificity differences, suggest that there is a potential for the design of molecules that might selectively block the acyl-CoA binding site.


Assuntos
Proteínas de Transporte/química , Proteínas de Transporte/metabolismo , Plasmodium falciparum/química , Sequência de Aminoácidos , Animais , Apoproteínas/química , Apoproteínas/genética , Apoproteínas/metabolismo , Sítios de Ligação , Proteínas de Transporte/genética , Bovinos , Cromatografia Líquida de Alta Pressão , Clonagem Molecular , Cristalografia por Raios X , Inibidor da Ligação a Diazepam , Desenho de Fármacos , Ligação de Hidrogênio , Ligantes , Modelos Moleculares , Dados de Sequência Molecular , Ressonância Magnética Nuclear Biomolecular , Plasmodium falciparum/genética , Conformação Proteica , Alinhamento de Sequência , Eletricidade Estática , Especificidade por Substrato
17.
EMBO J ; 20(13): 3322-32, 2001 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-11432820

RESUMO

The substrate specificities of Trypanosoma brucei and human (HeLa) GlcNAc-PI de-N-acetylases were determined using 24 substrate analogues. The results show the following. (i) The de-N-acetylases show little specificity for the lipid moiety of GlcNAc-PI. (ii) The 3'-OH group of the GlcNAc residue is essential for substrate recognition whereas the 6'-OH group is dispensable and the 4'-OH, while not required for recognition, cannot be epimerized or substituted. (iii) The parasite enzyme can act on analogues containing betaGlcNAc or aromatic N-acyl groups, whereas the human enzyme cannot. (iv) Three GlcNR-PI analogues are de-N-acetylase inhibitors, one of which is a suicide inhibitor. (v) The suicide inhibitor most likely forms a carbamate or thiocarbamate ester to an active site hydroxy-amino acid or Cys or residue such that inhibition is reversed by certain nucleophiles. These and previous results were used to design two potent (IC50 = 8 nM) parasite-specific suicide substrate inhibitors. These are potential lead compounds for the development of anti-protozoan parasite drugs.


Assuntos
Amidoidrolases/metabolismo , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Glicosilfosfatidilinositóis/biossíntese , Trypanosoma brucei brucei/enzimologia , Acetatos/metabolismo , Acetilação , Acetilglucosamina/análogos & derivados , Acetilglucosamina/química , Amidoidrolases/antagonistas & inibidores , Animais , Desenho de Fármacos , Inibidores Enzimáticos/química , Células HeLa , Humanos , Cinética , Conformação Molecular , Relação Estrutura-Atividade , Especificidade por Substrato
18.
Ear Hear ; 22(3): 173-81, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11409853

RESUMO

OBJECTIVE: During measurement of transient evoked otoacoustic emissions (TEOAEs), acoustic stimulation of the contralateral ear reduces or suppresses TEOAE amplitude. This is thought to be due to the inhibitory control that the medial efferent auditory nerve exerts on outer hair cell (OHC) function. The main aim of this study was to investigate the effect of cerebello-pontine angle (CPA) tumor on the medial efferent nerve pathways to both tumor and non-tumor ears by examining alterations in TEOAE amplitude that result from contralateral acoustic stimulation. DESIGN: Contralateral suppression of TEOAEs using broadband noise was measured preoperatively in 17 patients with unilateral CPA tumor and 17 normally hearing controls, matched for age and gender. RESULTS: The control ears demonstrated significantly more suppression than the tumor and non-tumor ears in the patient group. There was, however, no significant difference in suppression between the tumor and non-tumor ears, and the statistical correlation for suppression between them was high. There was no effect of gender, hearing threshold levels, or size and type of tumor on suppression, although there was an effect of age on suppression in both the control and patient groups where suppression reduced as age increased. Four of the 17 patients had TEOAEs, which were clearly present in the tumor ear despite substantial hearing loss, three of which had no measurable hearing. CONCLUSIONS: It is hypothesized that neural compression by CPA tumor disrupts the medial efferent nerve control mechanism to the OHCs of tumor ears. It also is hypothesized that neural compression reduces transmission of afferent nerve impulses from the tumor ear, which cross over to the medial olivo-cochlear complex and reduce the inhibitory control of OHC function in the non-tumor cochlea.


Assuntos
Neoplasias Cerebelares/fisiopatologia , Ângulo Cerebelopontino/fisiopatologia , Emissões Otoacústicas Espontâneas/fisiologia , Testes de Impedância Acústica/métodos , Estimulação Acústica/instrumentação , Adulto , Idoso , Audiometria de Tons Puros , Limiar Auditivo/fisiologia , Neoplasias Cerebelares/complicações , Neoplasias Cerebelares/cirurgia , Ângulo Cerebelopontino/cirurgia , Feminino , Células Ciliadas Auditivas Externas/fisiopatologia , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neurônios Aferentes/fisiologia , Neurônios Eferentes/fisiologia , Cuidados Pós-Operatórios , Cuidados Pré-Operatórios , Estudos Prospectivos , Índice de Gravidade de Doença
19.
J Am Coll Cardiol ; 37(5): 1359-66, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11300447

RESUMO

OBJECTIVES: This study examines the prevalence and hemodynamic determinants of mental stress-induced coronary vasoconstriction in patients undergoing diagnostic coronary angiography. BACKGROUND: Decreased myocardial supply is involved in myocardial ischemia triggered by mental stress, but the determinants of stress-induced coronary constriction and flow velocity responses are not well understood. METHODS: Coronary vasomotion was assessed in 76 patients (average age 59.9 +/- 10.4 years; eight women). Coronary flow velocity responses were assessed in 20 of the 76 patients using intracoronary Doppler flow. Repeated angiograms were obtained after a baseline control period, a 3-min mental arithmetic task and administration of 200 microg intracoronary nitroglycerin. Arterial blood pressure (BP) and heart rate assessments were made throughout the procedure. RESULTS: Mental stress resulted in significant BP and heart rate increases (p < 0.001). Coronary constriction (>0.15 mm) was observed in 11 of 59 patients with coronary artery disease (CAD) (18.6%). Higher mental stress pressor responses were associated with more constriction in diseased segments (rdeltaSBP = -0.26, rdeltaDBP = -0.30, rdeltaMAP = -0.29; p's < 0.05) but not with responses in nonstenotic segments. The overall constriction of diseased segments was not significant (p > 0.10), whereas a small but significant constriction occurred in nonstenotic segments (p = 0.04). Coronary flow velocity increased in patients without CAD (32.2%; p = 0.008), but not in patients with CAD (6.4%; p = ns). Cardiovascular risk factors were not predictive of stress-induced vasomotion in patients with CAD. CONCLUSIONS: Coronary vasoconstriction in angiographically diseased arteries varies with hemodynamic responses to mental arousal. Coronary flow responses are attenuated in CAD patients. Thus, combined increases in cardiac demand and concomitant reduced myocardial blood supply may contribute to myocardial ischemia with mental stress.


Assuntos
Circulação Coronária/fisiologia , Doença das Coronárias/psicologia , Hemodinâmica/fisiologia , Estresse Psicológico/complicações , Vasoconstrição/fisiologia , Idoso , Nível de Alerta/fisiologia , Atenção/fisiologia , Velocidade do Fluxo Sanguíneo/fisiologia , Pressão Sanguínea/fisiologia , Angiografia Coronária , Doença das Coronárias/fisiopatologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Resolução de Problemas/fisiologia , Fatores de Risco
20.
Biochim Biophys Acta ; 1531(1-2): 1-3, 2001 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-11278169

RESUMO

Pseudomonas acyl-CoA synthetase is shown to act on saturated dicarboxylic acids with a chain length of C10 or greater to produce conjugates containing a single CoA unit. The synthetase can, therefore, be used to generate novel acyl-CoA analogues for studies on proteins that utilise, bind to, or are modulated by acyl-CoAs.


Assuntos
Coenzima A Ligases/química , Ácidos Dicarboxílicos/química , Ácidos Graxos/química , Pseudomonas/enzimologia , Acil Coenzima A/síntese química , Especificidade da Espécie
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