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1.
J Consult Clin Psychol ; 88(9): 809-817, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32584117

RESUMO

Objective: Sudden gains during psychotherapy have been found to be predictive of positive treatment outcomes. Previous attempts at predicting occurrence of sudden gains have yielded equivocal findings. Recently, intraindividual variability in symptoms during treatment was suggested as a trans-therapeutic and trans-diagnostic predictor of sudden gains. The goal of the present study was to examine this predictor in Internet-delivered treatment for social anxiety disorder (SAD) and to examine whether this predictor predicts sudden gains when measured before treatment begins. Method: We examined data from a preregistered randomized controlled trial (RCT) of Internet-delivered cognitive-behavioral therapy (CBT) for SAD (n = 101). We measured variability in symptoms both within-treatment and before treatment (i.e. during waitlist). Results: Intraindividual variability in symptoms significantly predicted sudden gains both when measured before treatment or within-treatment and correctly classified 84% and 83% of individuals to sudden gains versus non-sudden gains status, respectively. Conclusions: Intraindividual variability in symptoms can predict sudden gains in Internet-delivered treatment for SAD, thus supporting its trans-diagnostic and trans-therapeutic nature. Predicting sudden gains before treatment begins has implications for treatment planning and clinical decision making as well as for personalized tailoring of interventions. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Assuntos
Terapia Cognitivo-Comportamental , Intervenção Baseada em Internet , Fobia Social/terapia , Adulto , Feminino , Humanos , Masculino , Fobia Social/psicologia , Resultado do Tratamento , Adulto Jovem
2.
Scand J Trauma Resusc Emerg Med ; 28(1): 56, 2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32571367

RESUMO

BACKGROUND: Previous studies have provided initial data suggesting that small-bore (SB, ≤ 14Fr) chest tubes have the same efficacy as large-bore (LB, > 14 Fr) chest tubes for acute hemothorax (HTX), but data continue to be lacking in the setting of delayed HTX. This study compared complications of SB chest tubes to LB tubes in patients with delayed HTX. METHODS: This was a retrospective observational study across 7.5 yrs. at 6 Level 1 trauma centers. Patients were included if 1) diagnosed with a HTX or > 1 rib fracture with bloody effusion from chest tube; 2) initial chest tube placed ≥36 h of hospital admission. Patients were excluded for hemopneumothoraces. The primary endpoint was having at least one of the following chest tube complications: tube replacement, VATS, tube falling out, tube clogging, pneumonia, retained HTX, pleural empyema. Secondary outcomes included chest tube output volume and drainage rate. Dependent/independent and parametric/non-parametric analyses were used to assess primary and secondary outcomes. RESULTS: There were 160 SB patients (191 tubes) and 60 LB patients (72 tubes). Both comparison groups were similar in multiple demographic, injury, clinical features. The median (IQR) tube size for each group was as follows: SB [12 Fr (12-14)] and LB [32 Fr (28-32)]. The risk of having at least one chest tube complication was similar for LB and SB chest tubes (14% vs. 18%, p = 0.42). LB tubes had significantly larger risk of VATS, while SB tubes had significantly higher risk of pneumonia. SB tubes had significantly slower least squares (LS) mean initial output drainage rate compared to LB tubes (52.2 vs. 213.4 mL/hour, p < 0.001), but a non-parametric analysis suggested no significant difference in median drainage rates between groups 39.7 [23.5-242.0] mL/hr. vs. 38.6 [27.5-53.8], p = 0.81. LB and SB groups had similar initial output volume (738.0 mL vs. 810.9, p = 0.59). CONCLUSIONS: There was no clearly superior chest tube diameter size; both chest tube sizes demonstrated risks and benefits. Clinicians must be aware of these potential tradeoffs when deciding on the diameter of chest tube for the treatment of delayed HTXs.


Assuntos
Tubos Torácicos/efeitos adversos , Hemotórax/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Drenagem , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/epidemiologia , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida/estatística & dados numéricos , Fatores de Tempo , Centros de Traumatologia , Estados Unidos/epidemiologia , Adulto Jovem
3.
J Orthop Surg Res ; 14(1): 411, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801568

RESUMO

BACKGROUND: Most guidelines recommend both pelvic packing (PP) and angioembolization for hemodynamically unstable pelvic fractures, however their sequence varies. Some argue to use PP first because orthopaedic surgeons are more available than interventional radiologists; however, there is no data confirming this. METHODS: This cross-sectional survey of 158 trauma medical directors at US Level I trauma centers collected the availability of orthopaedic surgeons and interventional radiologists, the number of orthopaedic trauma surgeons trained to manage pelvic fractures, and priority treatment sequence for hemodynamically unstable pelvic fractures. The study objective was to compare the availability of orthopaedic surgeons to interventional radiologists and describe how the availability of orthopaedic surgeons and interventional radiologists affects the treatment sequence for hemodynamically unstable pelvic fractures. Fisher's exact, chi-squared, and Kruskal-Wallis tests were used, alpha = 0.05. RESULTS: The response rate was 25% (40/158). Orthopaedic surgeons (86%) were on-site more often than interventional radiologists (54%), p = 0.003. Orthopaedic surgeons were faster to arrive 39% of the time, and interventional radiologists were faster to arrive 6% of the time. There was a higher proportion of participants who prioritized PP before angioembolization at centers with above the average number (> 3) of orthopaedic trauma surgeons trained to manage pelvic fractures, as among centers with equal to or below average, p = 0.02. Arrival times for orthopaedic surgeons did not significantly predict prioritization of angioembolization or PP. CONCLUSIONS: Our results provide evidence that orthopaedic surgeons typically are more available than interventional radiologists but contrary to anecdotal evidence most participants used angioembolization first. Familiarity with the availability of orthopaedic surgeons and interventional radiologists may contribute to individual trauma center's treatment sequence.


Assuntos
Fraturas Ósseas/terapia , Cirurgiões Ortopédicos/provisão & distribuição , Ossos Pélvicos/lesões , Admissão e Escalonamento de Pessoal , Radiologistas/provisão & distribuição , Inquéritos e Questionários , Embolização Terapêutica/métodos , Embolização Terapêutica/tendências , Fraturas Ósseas/epidemiologia , Hemodinâmica/fisiologia , Humanos , Cirurgiões Ortopédicos/tendências , Admissão e Escalonamento de Pessoal/tendências , Diretores Médicos/tendências , Radiologistas/tendências , Centros de Traumatologia/tendências , Resultado do Tratamento , Estados Unidos/epidemiologia
4.
Proteomics ; 19(14): e1900028, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31168896

RESUMO

Adaptation to the environment during development influences the life-long survival of an animal. While brain-wide proteomic changes are expected to underlie such experience-driven physiological and behavioral flexibility, a comprehensive overview of the nature and extent of the proteomic regulation following an environmental challenge during development is currently lacking. In this study, the brain proteome of larval zebrafish is identified and it is determined how it is altered by an exposure to a natural and physical environmental challenge, namely prolonged exposure to strong water currents. A comprehensive larval zebrafish brain proteome is presented here. Furthermore, 57 proteins that are regulated by the exposure to an environmental challenge are identified, which cover multiple functions including neuronal plasticity, the stress response, axonal growth and guidance, spatial learning, and energy metabolism. These represent candidate proteins that may play crucial roles for the adaption to an environmental challenge during development.


Assuntos
Encéfalo/metabolismo , Proteoma/metabolismo , Proteômica/métodos , Animais , Larva , Peixe-Zebra
5.
Hong Kong Med J ; 23(5): 441-5, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28126972

RESUMO

INTRODUCTION: Intravenous infusion of lignocaine has emerged in recent years as a feasible, cost-effective, and safe method to provide postoperative analgesia. There is, however, no literature about this perioperative pain control modality in Chinese patients. This study aimed to determine whether perioperative intravenous lignocaine safely reduces postoperative pain, shortens postoperative ileus, and reduces the length of hospital stay in laparoscopic colorectal surgery. METHODS: Between September 2012 and May 2015, 16 patients who underwent elective laparoscopic resection of colorectal cancer and received a 1% lignocaine infusion for 24 hours postoperatively were studied. After surgery, categorical pain scores were obtained immediately, followed by hourly pain scores at rest. Pain scores at rest and with mobilisation, and patient satisfaction score were documented on postoperative day 1. Return of bowel function was measured by time of first flatus and bowel opening. The patient's rehabilitation was assessed by time taken to tolerate diet, full mobilisation, and length of hospital stay. RESULTS: The median (interquartile range) self-reported pain scores at 2 hours and 6 hours after surgery were 1.5 (0-4) and 2 (0-3), respectively. The median pain scores at rest and mobilisation on postoperative day 1 were 1 (0-2.5) and 2 (2.5-5), respectively, with a median satisfaction score of 7.5 (7-9). The median times to first flatus and first bowel opening were 21 (18-35) hours and 3 (1-3) days, respectively. No patient had postoperative ileus. The median times to tolerating diet and mobilisation were 1 (1-1) day and 2 (2-3) days, respectively. The median postoperative stay was 6 (5-8) days. CONCLUSIONS: Intravenous lignocaine is a safe and effective postoperative analgesic in a Chinese population. It enhances the rehabilitation process for patients following laparoscopic resection of colorectal cancer.


Assuntos
Anestésicos Locais/uso terapêutico , Colectomia , Neoplasias Colorretais/reabilitação , Lidocaína/uso terapêutico , Dor Pós-Operatória/prevenção & controle , Idoso , Anestésicos Locais/administração & dosagem , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Infusões Intravenosas , Laparoscopia , Lidocaína/administração & dosagem , Masculino , Medição da Dor , Assistência Perioperatória , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Resultado do Tratamento
6.
Annu Int Conf IEEE Eng Med Biol Soc ; 2016: 2847-2850, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28268910

RESUMO

During routine sleep diagnostic procedure, sleep is broadly divided into three states: rapid eye movement (REM), non-REM (NREM) states, and wake, frequently named macro-sleep stages (MSS). In this study, we present a pioneering attempt for MSS detection using full night audio analysis. Our working hypothesis is that there might be differences in sound properties within each MSS due to breathing efforts (or snores) and body movements in bed. In this study, audio signals of 35 patients referred to a sleep laboratory were recorded and analyzed. An additional 178 subjects were used to train a probabilistic time-series model for MSS staging across the night. The audio-based system was validated on 20 out of the 35 subjects. System accuracy for estimating (detecting) epoch-by-epoch wake/REM/NREM states for a given subject is 74% (69% for wake, 54% for REM, and 79% NREM). Mean error (absolute difference) was 36±34 min for detecting total sleep time, 17±21 min for sleep latency, 5±5% for sleep efficiency, and 7±5% for REM percentage. These encouraging results indicate that audio-based analysis can provide a simple and comfortable alternative method for ambulatory evaluation of sleep and its disorders.


Assuntos
Algoritmos , Movimento , Polissonografia/métodos , Sons Respiratórios , Fases do Sono , Vigília , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Reconhecimento Automatizado de Padrão/métodos , Som , Adulto Jovem
7.
Annu Int Conf IEEE Eng Med Biol Soc ; 2016: 3207-3210, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28268990

RESUMO

Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder. Previous studies associated OSA with anatomical abnormalities of the upper respiratory tract that may be reflected in the acoustic characteristics of speech. We tested the hypothesis that the speech signal carries essential information that can assist in early assessment of OSA severity by estimating apnea-hypopnea index (AHI). 198 men referred to routine polysomnography (PSG) were recorded shortly prior to sleep onset while reading a one-minute speech protocol. The different parts of the speech recordings, i.e., sustained vowels, short-time frames of fluent speech, and the speech recording as a whole, underwent separate analyses, using sustained vowels features, short-term features, and long-term features, respectively. Applying support vector regression and regression trees, these features were used in order to estimate AHI. The fusion of the outputs of the three subsystems resulted in a diagnostic agreement of 67.3% between the speech-estimated AHI and the PSG-determined AHI, and an absolute error rate of 10.8 events/hr. Speech signal analysis may assist in the estimation of AHI, thus allowing the development of a noninvasive tool for OSA screening.


Assuntos
Acústica , Índice de Gravidade de Doença , Processamento de Sinais Assistido por Computador , Apneia Obstrutiva do Sono/diagnóstico , Fala , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Apneia Obstrutiva do Sono/fisiopatologia , Adulto Jovem
8.
Artigo em Inglês | MEDLINE | ID: mdl-25871081

RESUMO

The role of spatially correlated mechanical elements in the failure behavior of heterogeneous materials represented by fiber bundle models (FBMs) was evaluated systematically for different load redistribution rules. Increasing the range of spatial correlation for FBMs with local load sharing is marked by a transition from ductilelike failure characteristics into brittlelike failure. The study identified a global failure criterion based on macroscopic properties (external load and cumulative damage) that is independent of spatial correlation or load redistribution rules. This general metric could be applied to assess the mechanical stability of complex and heterogeneous systems and thus provide an important component for early warning of a class of geophysical ruptures.

9.
Br J Radiol ; 86(1030): 20130253, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23966375

RESUMO

OBJECTIVE: To evaluate the feasibility of using three-dimensional (3D) ultrasound to assess the anatomy of the airway. METHODS: 11 young volunteers were recruited for 3D ultrasound and MRI of the airway. 3D ultrasound data were obtained from the level of the true vocal cords, cricoid cartilage and upper trachea. Multiplanar 3D ultrasound images were rendered and compared visually with corresponding MRI and cadaver anatomical sections. The anteroposterior (AP) and transverse diameter of the subglottic space and transverse diameter of the upper trachea were also measured in the 3D ultrasound and MR images and compared. RESULTS: The airway anatomy was clearly delineated in the multiplanar 3D ultrasound images. It was also possible to identify the cricothyroid junction, and a simple method to measure the AP diameter of the subglottic space using this landmark is described. We were also able to accurately measure the transverse diameter of the upper trachea, but the transverse diameter of the subglottic space was overestimated using ultrasound. There was a strong correlation for the AP diameter measurement (r=0.94, p<0.05) and moderate correlation for the transverse diameter measurement (r=0.82, p=0.002) of the subglottic space, and a strong correlation for the transverse diameter measurement (r=0.91, p<0.05) of the upper trachea, in the ultrasound and MR images. CONCLUSION: The anatomy of the adult airway can be assessed using 3D ultrasound. It can also be used to accurately measure the AP diameter of the subglottic space and the transverse diameter of the upper trachea. ADVANCES IN KNOWLEDGE: This is the first report to describe the use of 3D ultrasound to evaluate the anatomy of the upper airway and accurately measure the AP diameter of the subglottic space and the transverse diameter of the upper trachea.


Assuntos
Cartilagem Cricoide/anatomia & histologia , Cartilagem Cricoide/diagnóstico por imagem , Traqueia/anatomia & histologia , Traqueia/diagnóstico por imagem , Prega Vocal/anatomia & histologia , Prega Vocal/diagnóstico por imagem , Adulto , Estudos de Viabilidade , Feminino , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Masculino , Projetos Piloto , Ultrassonografia , Adulto Jovem
10.
J Colloid Interface Sci ; 391: 135-41, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23123032

RESUMO

Porous media containing sharp wettability discontinuities may occur in natural systems due to depositional processes, accumulation of organic layers or modification of soil wettability following intense forest fires all of which are known to significantly modify water flow and transport processes. We studied evaporation from sand columns containing hydraulically-interacting domains with sharp wettability contrasts. We employed neutron transmission technique to map liquid phase dynamics during evaporation, and conducted laboratory experiments to evaluate evaporative fluxes affected by interactions across wettability contrast. We explained the preferential drying front displacement in the hydrophobic domain and the spatial extent of capillary flow supporting the vaporization plane using a physically-based model. The model provides description of observed liquid phase patterns and dynamics observed in neutron radiography measurements and evaporative fluxes from laboratory experiments. Our results provide new insights into evaporation induced capillary exchange and preferential liquid phase distribution during evaporation from hydraulically interacting vertical porous domains with differing wettability properties and offer opportunities for design of selectively drying of porous media in natural and engineered systems.

11.
Blood ; 120(2): 366-75, 2012 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-22645179

RESUMO

APOBEC3 proteins catalyze deamination of cytidines in single-stranded DNA (ssDNA), providing innate protection against retroviral replication by inducing deleterious dC > dU hypermutation of replication intermediates. APOBEC3G expression is induced in mitogen-activated lymphocytes; however, no physiologic role related to lymphoid cell proliferation has yet to be determined. Moreover, whether APOBEC3G cytidine deaminase activity transcends to processing cellular genomic DNA is unknown. Here we show that lymphoma cells expressing high APOBEC3G levels display efficient repair of genomic DNA double-strand breaks (DSBs) induced by ionizing radiation and enhanced survival of irradiated cells. APOBEC3G transiently accumulated in the nucleus in response to ionizing radiation and was recruited to DSB repair foci. Consistent with a direct role in DSB repair, inhibition of APOBEC3G expression or deaminase activity resulted in deficient DSB repair, whereas reconstitution of APOBEC3G expression in leukemia cells enhanced DSB repair. APOBEC3G activity involved processing of DNA flanking a DSB in an integrated reporter cassette. Atomic force microscopy indicated that APOBEC3G multimers associate with ssDNA termini, triggering multimer disassembly to multiple catalytic units. These results identify APOBEC3G as a prosurvival factor in lymphoma cells, marking APOBEC3G as a potential target for sensitizing lymphoma to radiation therapy.


Assuntos
Citidina Desaminase/metabolismo , Reparo do DNA/fisiologia , Linfoma/metabolismo , Linfoma/radioterapia , Tolerância a Radiação/fisiologia , Desaminase APOBEC-3G , Domínio Catalítico , Linhagem Celular Tumoral , Sobrevivência Celular , Citidina Desaminase/antagonistas & inibidores , Citidina Desaminase/química , Citidina Desaminase/genética , Quebras de DNA de Cadeia Dupla , Reparo do DNA por Junção de Extremidades , DNA de Neoplasias/metabolismo , DNA de Neoplasias/efeitos da radiação , Técnicas de Silenciamento de Genes , Humanos , Linfoma/patologia , Microscopia de Força Atômica , Multimerização Proteica
12.
AJNR Am J Neuroradiol ; 32(5): 864-8, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21310859

RESUMO

BACKGROUND AND PURPOSE: Patients with acute ischemic stroke require immediate medical treatment, and a CT to rule out hemorrhage is required before tPA. We adapted our protocol to include multimodal CT: unenhanced CT, CTA, and PCT. The purpose of this study was to determine whether multimodal CT imaging delays initiation of IV tPA beyond 60 minutes from hospital arrival. MATERIALS AND METHODS: All patients admitted during 3 years through the ED with a stroke alert and time from symptom onset to hospital arrival <2.5 hours were included. We examined 2 subgroups (multimodal CT versus unenhanced CT) to determine whether multimodal CT delayed tPA administration. Logistic regression was used to identify variables that predicted tPA within 60 minutes. RESULTS: There were 123 patients in the analysis, including 108 patients who were examined with multimodal CT. The median time from arrival to tPA was 56 minutes and was shorter for patients examined with multimodal CT (55 versus 78 minutes, P = .02). After adjustment, variables that were associated with tPA administration within 60 minutes included prehospital stroke alert (OR = 3.47, P = .03), time to CT (OR = 0.94, P = .01), and onset-to-arrival time (OR = 1.02, P = .04). There was no statistically significant difference in the odds of receiving timely tPA for multimodal versus unenhanced CT (OR = 3.99, P = .07). CONCLUSIONS: In our single-center experience, the use of multimodal imaging in patients with acute stroke did not delay IV tPA beyond 60 minutes. Further study is needed to assess the feasibility of the routine use of multimodal imaging in the acute stroke setting.


Assuntos
Angiografia Cerebral/métodos , Fibrinolíticos/administração & dosagem , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/administração & dosagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Injeções Intravenosas , Masculino , Técnica de Subtração , Fatores de Tempo , Resultado do Tratamento
13.
Phys Rev E Stat Nonlin Soft Matter Phys ; 81(4 Pt 2): 046308, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20481828

RESUMO

Evaporation from porous media involves complex pore scale transport processes affecting liquid phase distribution and fluxes. Often, the initial evaporation rate is nearly constant and supplied by capillary flow from wetted zones below to the surface. Sustaining constant flow against gravity hinges on an upward capillary gradient and on liquid phase continuity with hydraulic conductivity sufficient for supplying evaporative flux. The pore scale liquid phase adjustments during evaporative displacement necessary for maintaining a constant flux have been postulated but rarely measured. In this study we employed detailed imaging using x-ray synchrotron radiation to study liquid phase distribution and dynamics at the most sensitive domain just below the surface of evaporating sand columns. Three-dimensional images at a resolution of 7 microns were obtained from sand column (mean particle size 0.6 mm) initially saturated with calcium iodide solution (4% by mass) to enhance image contrast. Detailed imaging of near-surface liquid phase distribution during evaporation confirmed phase continuity at micrometric scale and provided quantitative estimates of liquid conductance in agreement with values required to supply evaporative flux. Temporal variations in bulk salt concentrations determined from x-ray attenuation were proportional to evaporative water mass loss. Highly resolved salt concentration images revealed existence of evaporating chimneys that supply the bulk of evaporative demand. Delineated mass loss dynamics and salt distribution measured by the x-ray attenuation were in reasonable agreement with a simplified analytical convection-diffusion model for salt dynamics during evaporation from porous media.

14.
Phys Rev E Stat Nonlin Soft Matter Phys ; 76(2 Pt 2): 026311, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17930146

RESUMO

Water flow between porous grains varies widely depending on the water distribution in contacts between grains. The hydraulic behavior of contacts varies from highly conductive when water fills the contacts to a bottleneck to flow as water pressure drops and contact asperities rapidly drain. Such changes greatly impact the hydraulic conductivity of porous grain packs such as aggregated soil. The dominant driving force of water flow across contacts is capillarity, often quantified relative to gravity and viscous forces using the capillary and Bond numbers. For fast water infiltration, viscous forces dominate. For simplicity we modeled the water distribution between spherical porous grains whose surfaces are covered by spherical bumps of much smaller radii. We provide experimental evidence obtained by neutron radiography and synchrotron-based x-ray tomographic microscopy documenting transitions in the flow behavior across contacts.

15.
J Cardiovasc Pharmacol ; 39(5): 722-8, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-11973416

RESUMO

The N-terminus region of human albumin binds strongly to trace metals (Co, Cu, Ni). Ischemia, acidosis and reperfusion can cause a marked increase in plasma free Cu and its normal regulation by plasma proteins may be overwhelmed and predispose to oxidative injury by Cu-catalyzed oxyradical production. H4DUS60131 is an analogue of the N-terminus of human albumin, it binds copper tightly and in vitro, is a potent inhibitor of Cu-catalyzed radical formation. We have tested the ability of H4DUS60131 to reduce injury during ischemia and reperfusion in isolated blood-perfused rat hearts (n = 6/group) subjected to 20-min aerobic perfusion, followed by a 2-min infusion of saline or saline plus H4DUS60131. Following infusion, hearts were subjected to 30-min global ischemia plus 40-min reperfusion. The 2-min infusion was repeated in both groups at the start of reperfusion. In the vehicle controls, left ventricular developed pressure recovered to only 15.3 +/- 3.2%, whereas the H4DUS60131 group recovered to 50.5 +/- 9.3% (p < 0.005). The H4DUS60131 group normalised their left ventricular end diastolic pressure more quickly and completely than the controls (44.1 +/- 11.5 vs. 91.5 +/- 5.5 mm Hg). In conclusion, H4DUS60131 greatly improves the recovery of the rat heart from ischemia and reperfusion and may represent a novel approach to the limitation of myocardial injury.


Assuntos
Isquemia Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Albumina Sérica/uso terapêutico , Oligoelementos/efeitos adversos , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Técnicas In Vitro , Masculino , Contração Miocárdica/efeitos dos fármacos , Contração Miocárdica/genética , Isquemia Miocárdica/fisiopatologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Perfusão/instrumentação , Perfusão/métodos , Ratos , Ratos Wistar , Albumina Sérica/química , Albumina Sérica/metabolismo , Albumina Sérica/farmacologia , Oligoelementos/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos , Função Ventricular Esquerda/fisiologia
16.
Oecologia ; 130(2): 173-184, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28547139

RESUMO

The significance of soil water redistribution facilitated by roots (an extension of "hydraulic lift", here termed hydraulic redistribution) was assessed for a stand of Artemisia tridentata using measurements and a simulation model. The model incorporated water movement within the soil via unsaturated flow and hydraulic redistribution and soil water loss from transpiration. The model used Buckingham-Darcy's law for unsaturated flow while hydraulic redistribution was developed as a function of the distribution of active roots, root conductance for water, and relative soil-root (rhizosphere) conductance for water. Simulations were conducted to compare model predictions with time courses of soil water potential at several depths, and to evaluate the importance of root distribution, soil hydraulic conductance and root xylem conductance on transpiration rates and the dynamics of soil water. The model was able to effectively predict soil water potential during a summer drying cycle, and the rapid redistribution of water down to 1.5 m into the soil column after rainfall events. Results of simulations indicated that hydraulic redistribution could increase whole canopy transpiration over a 100-day drying cycle. While the increase was only 3.5% over the entire 100-day period, hydraulic redistribution increased transpiration up to 20.5% for some days. The presence of high soil water content within the lower rooting zone appears to be necessary for sizeable increases in transpiration due to hydraulic redistribution. Simulation results also indicated that root distributions with roots concentrated in shallow soil layers experienced the greatest increase in transpiration due to hydraulic redistribution. This redistribution had much less effect on transpiration with more uniform root distributions, higher soil hydraulic conductivity and lower root conductivity. Simulation results indicated that redistribution of water by roots can be an important component in soil water dynamics, and the model presented here provides a useful approach to incorporating hydraulic redistribution into larger models of soil processes.

18.
Biochem Biophys Res Commun ; 284(3): 856-62, 2001 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-11396981

RESUMO

Copper mobilization and redox activity form damaging reactive oxygen species (ROS) and are implicated in the pathogenesis of ischemia-reperfusion injury, chronic inflammation, Alzheimer's disease, aging, and cancer. Protein sequestration of Cu(II) ions has been shown to prevent ROS-generating reactions. The first four amino acids of the N-terminus of human albumin, Asp-Ala-His-Lys (DAHK), form a tight binding site for Cu(II) ions. We synthesized several analogs, including the enantiomer d-DAHK, to study their effects on copper-induced hydroxyl radical and superoxide formation in the presence of ascorbate. d-DAHK prevented thiobarbituric acid-reactive species (TBARS) formation within physiological and acidic pH ranges (7.5-6.5) and inhibited low-density lipoprotein lipid peroxidation. A d-DAHK/Cu complex exhibited superoxide dismutase-like activity by significantly inhibiting superoxide formation. These in vitro results suggest that d-DAHK may shift the Cu(II)-binding equilibrium from the exchangeable Cu(II) pool to the tightly-bound, nonexchangeable pool, prevent ROS formation, and potentially provide therapeutic benefit for ROS-related diseases.


Assuntos
Albuminas/farmacologia , Cobre/farmacologia , Oligopeptídeos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Humanos , Radical Hidroxila/metabolismo , Cinética , Peroxidação de Lipídeos , Oligopeptídeos/metabolismo , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/análise
19.
Am Heart J ; 141(6): 985-91, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11376314

RESUMO

BACKGROUND: Previous reports suggest that ischemic conditions rapidly reduce the capacity of human albumin to bind exogenous cobalt. A new assay based on human albumin-cobalt binding (ACB) may help detect early myocardial ischemia. We investigated altered ACB during the first 24 hours after transient ischemia induced during elective percutaneous transluminal coronary angioplasty (PTCA). We then compared ACB assay results with creatine kinase isoenzyme (CK-MB), myoglobin, and cardiac troponin I (cTn-I) values after PTCA. METHODS AND RESULTS: In 41 patients undergoing elective PTCA, plasma samples were tested for the ACB assay, CK-MB, myoglobin, and cTn-I before, immediately after, and 6 and 24 hours after PTCA. Thirteen additional patients served as a control group with albumin-cobalt assays performed before and after diagnostic coronary catheterization without angioplasty. ACB assay results demonstrated a significant mean percent difference (10.1%) immediately after PTCA compared with baseline (P < .000001) and returned to baseline by 6 hours after PTCA. ACB assay differences immediately after PTCA were significantly greater than in the control group (10.1% vs -0.9%, P < .001). Mean CK-MB, myoglobin, and cTn-I values were not elevated above baseline immediately after PTCA but were significantly elevated above baseline 6 and 24 hours after PTCA. CONCLUSIONS: These preliminary results suggest that human albumin undergoes a significant reduction in its capacity to bind exogenous cobalt soon after transient coronary occlusion during human PTCA and before significant elevations of CK-MB, myoglobin, or cTn-I. Further confirmatory investigations are warranted to determine if the ACB assay is a useful diagnostic test for early myocardial ischemia.


Assuntos
Angioplastia Coronária com Balão , Biomarcadores/sangue , Cobalto , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/terapia , Albumina Sérica , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Cobalto/metabolismo , Creatina Quinase/sangue , Creatina Quinase Forma MB , Feminino , Humanos , Isoenzimas/sangue , Masculino , Pessoa de Meia-Idade , Mioglobina/sangue , Período Pós-Operatório , Estudos Prospectivos , Ligação Proteica , Albumina Sérica/metabolismo , Troponina I/sangue
20.
Biochem Biophys Res Commun ; 282(1): 356-60, 2001 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-11264015

RESUMO

Both DNA and the telomeric sequence are susceptible to copper-mediated reactive oxygen species (ROS) damage, particularly damage attributed to hydroxyl radicals. In this study, ROS-induced DNA double strand breaks and telomere shortening were produced by exposure to copper and ascorbic acid. Asp-Ala-His-Lys (DAHK), a specific copper chelating tetrapeptide d-analog of the N-terminus of human albumin, attenuated DNA strand breaks in a dose dependent manner. d-DAHK, at a ratio of 4:1 (d-DAHKCu), provided complete protection of isolated DNA from double strand breaks and, at a ratio of 2:1 (d-DAHKCu), completely protected DNA in Raji cells exposed to copper/ascorbate. Southern blots of DNA treated with copper/ascorbate showed severe depletion and shortening of telomeres and Raji cell treated samples showed some conservation of telomere sequences. d-DAHK provided complete telomere length protection at a ratio of 2:1 (d-DAHKCu). The human albumin N-terminus analog, d-DAHK, protects DNA and telomeres against copper-mediated ROS damage and may be a useful therapeutic adjunct in ROS disease processes.


Assuntos
Cobre/antagonistas & inibidores , Dano ao DNA , Oligopeptídeos/farmacologia , Estresse Oxidativo , Telômero/efeitos dos fármacos , Linhagem Celular , Cobre/farmacologia , DNA/efeitos dos fármacos , Humanos
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