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1.
Phys Rev Lett ; 132(21): 215201, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38856280

RESUMO

We investigate the propagation of Alfvén waves in the solar chromosphere, distinguishing between upward and downward propagating waves. We find clear evidence for the reflection of waves in the chromosphere and differences in propagation between cases with waves interpreted to be resonant or nonresonant with the overlying coronal structures. This establishes the wave connection to coronal element abundance anomalies through the action of the wave ponderomotive force on the chromospheric plasma, which interacts with chromospheric ions but not neutrals, thereby providing a novel mechanism of ion-neutral separation. This is seen as a "first ionization potential effect" when this plasma is lifted into the corona, with implications elsewhere on the Sun for the origin of the slow speed solar wind and its elemental composition.

2.
Phys Rev Lett ; 131(10): 106301, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37739351

RESUMO

The dynamical phase diagram of interacting disordered systems has seen substantial revision over the past few years. Theory must now account for a large prethermal many-body localized regime in which thermalization is extremely slow, but not completely arrested. We derive a quantitative description of these dynamics in short-ranged one-dimensional systems using a model of successive many-body resonances. The model explains the decay timescale of mean autocorrelators, the functional form of the decay-a stretched exponential-and relates the value of the stretch exponent to the broad distribution of resonance timescales. The Jacobi method of matrix diagonalization provides numerical access to this distribution, as well as a conceptual framework for our analysis. The resonance model correctly predicts the stretch exponents for several models in the literature. Successive resonances may also underlie slow thermalization in strongly disordered systems in higher dimensions, or with long-range interactions.

3.
Phys Rev Lett ; 128(18): 183602, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35594101

RESUMO

The striking nonlinear effects exhibited by cavity QED systems make them a powerful tool in modern condensed matter and atomic physics. A recently discovered example is the quantized pumping of energy into a cavity by a strongly coupled, periodically driven spin. We uncover a remarkable feature of these energy pumps: they coherently translate, or boost, a quantum state of the cavity in the Fock basis. Current optical cavity and circuit QED experiments can realize the required Hamiltonian in a rotating frame. Boosting thus enables the preparation of highly excited nonclassical cavity states in near-term experiments.

4.
Sensors (Basel) ; 22(20)2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36298277

RESUMO

Ocean Acidification (OA) is negatively affecting the physiological processes of marine organisms, altering biogeochemical cycles, and changing chemical equilibria throughout the world's oceans. It is difficult to measure pH broadly, in large part because accurate pH measurement technology is expensive, bulky, and requires technical training. Here, we present the development and evaluation of a hand-held, affordable, field-durable, and easy-to-use pH instrument, named the pHyter, which is controlled through a smartphone app. We determine the accuracy of pH measurements using the pHyter by comparison with benchtop spectrophotometric seawater pH measurements, measurement of a certified pH standard, and comparison with a proven in situ instrument, the iSAMI-pH. These results show a pHyter pH measurement accuracy of ±0.046 pH or better, which is on par with interlaboratory seawater pH measurement comparison experiments. We also demonstrate the pHyter's ability to conduct both temporal and spatial studies of coastal ecosystems by presenting data from a coral reef and a bay, in which the pHyter was used from a kayak. These studies showcase the instrument's portability, applicability, and potential to be used for community science, STEM education, and outreach, with the goal of empowering people around the world to measure pH in their own backyards.


Assuntos
Ecossistema , Água do Mar , Água do Mar/química , Prótons , Concentração de Íons de Hidrogênio , Fótons , Oceanos e Mares , Dióxido de Carbono/análise
5.
Phys Rev Lett ; 126(10): 106805, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33784118

RESUMO

We derive a topological classification of the steady states of d-dimensional lattice models driven by D incommensurate tones. Mapping to a unifying (d+D)-dimensional localized model in frequency space reveals anomalous localized topological phases (ALTPs) with no static analog. While the formal classification is determined by d+D, the observable signatures of each ALTP depend on the spatial dimension d. For each d, with d+D=3, we identify a quantized circulating current and corresponding topological edge states. The edge states for a driven wire (d=1) function as a quantized, nonadiabatic energy pump between the drives. We design concrete models of quasiperiodically driven qubits and wires that achieve ALTPs of several topological classes. Our results provide a route to experimentally access higher dimensional ALTPs in driven low-dimensional systems.

6.
BMC Musculoskelet Disord ; 22(1): 797, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530784

RESUMO

BACKGROUND: Osteoarthritis (OA) is the most prevalent form of joint disease and commonly affects the hip. Hip OA is associated with a high socioeconomic burden. Intra-articular hyaluronic acid (HA) injection may be of benefit but quality evidence for HA use in hip OA is lacking. The purpose of this study was to assess the safety and efficacy of ultrasound guided injection of a high molecular weight, non-animal derived, stabilised HA (NASHA) in patients with mild to moderate hip OA. METHODS: This single site study is an analysis of prospectively collected outcome data for 87 consecutive patients over a 2-year period who received a single HA (Durolane) injection for symptomatic hip OA. Inclusion criteria were male or female patients over 18-years of age with mild to moderate hip OA on x-ray. Patients with severe hip OA were excluded. The primary outcome measure was a modified Harris Hip Score (mHHS) questionnaire at baseline and 6-weeks with a minimal clinically important difference (MCID) of 10 points. All adverse events were recorded and assessed. RESULTS: Data from 87 patients, 49 women and 38 men with mean age of 54 (SD = 10.8) were analysed. At baseline, mean mHHS was 58.47 (SD 14.31). At the 6 week follow up, mean mHHS improved to 71.30 (SD 16.46), a difference of 12.83 (p < 0.01). This was greater than the MCID of 10. No significant adverse events were encountered. Five patients reported short-lived injection site pain. CONCLUSION: A single injection of HA (NASHA) in the setting of hip joint OA was both safe and efficacious in this 87 patient cohort. Improvement in pain and function as measured with mHHS was statistically significant and reached the MCID of 10. TRIAL REGISTRATION: The study was retrospectively registered on the 1st of February 2021 in the Australian New Zealand Clinical Trials Registry with registry number ACTRN12621000098831 . All research was performed in accordance with the Declaration of Helsinki.


Assuntos
Osteoartrite do Quadril , Osteoartrite do Joelho , Adulto , Austrália , Feminino , Humanos , Ácido Hialurônico/efeitos adversos , Injeções Intra-Articulares/efeitos adversos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/diagnóstico por imagem , Osteoartrite do Quadril/tratamento farmacológico , Osteoartrite do Joelho/tratamento farmacológico , Resultado do Tratamento
7.
Phys Rev Lett ; 117(17): 170502, 2016 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-27824464

RESUMO

Achieving error rates that meet or exceed the fault-tolerance threshold is a central goal for quantum computing experiments, and measuring these error rates using randomized benchmarking is now routine. However, direct comparison between measured error rates and thresholds is complicated by the fact that benchmarking estimates average error rates while thresholds reflect worst-case behavior when a gate is used as part of a large computation. These two measures of error can differ by orders of magnitude in the regime of interest. Here we facilitate comparison between the experimentally accessible average error rates and the worst-case quantities that arise in current threshold theorems by deriving relations between the two for a variety of physical noise sources. Our results indicate that it is coherent errors that lead to an enormous mismatch between average and worst case, and we quantify how well these errors must be controlled to ensure fair comparison between average error probabilities and fault-tolerance thresholds.

8.
Endocrinology ; 148(2): 886-95, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17110423

RESUMO

Blockade of advanced glycation end product (AGE) accumulation with alagebrium with concomitant angiotensin converting enzyme inhibition was tested for effects on renal function and on other postulated mediators of diabetic renal disease including the renin-angiotensin system, AGEs, mitochondrial and cytosolic oxidative stress, and intracellular signaling molecules. Sprague Dawley rats were rendered diabetic with streptozocin and followed consecutively for 32 wk with nondiabetic controls. Groups were treated with ramipril (1 mg/kg.d; wk 0-32); alagebrium (10 mg/kg.d; wk 16-32); or a combination of both. Although individual treatments had significant effects on albuminuria, no further improvements were seen with combination therapy. Changes in urinary vascular endothelial growth factor excretion mirrored those seen in albuminuria. Diabetes was associated with suppression of circulating angiotensin II in the context of increased circulating and renal levels of the AGE, carboxymethyllysine. All treatments attenuated circulating but not renal carboxymethyllysine levels. The renal gene expression of AGE receptor 1 and soluble receptor for advanced glycation end products were markedly reduced by diabetes and normalized with alagebrium. Diabetes induced renal mitochondrial oxidative stress, which was reduced with alagebrium. In the cytosol, both therapies were equally effective in reducing reactive oxygen species production. Increases in membranous protein kinase C activity in diabetes were attenuated by all treatments, whereas diabetes-associated increases in nuclear factor-kappaB p65 translocation remained unaltered by any therapy. It is evident that renin-angiotensin system blockade and AGE inhibition have specific effects. However, many of their downstream effects appear to be similar, suggesting that their renoprotective benefits may ultimately involve common pathways and key points of convergence, which could be important targets for new therapies in diabetic nephropathy.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Ramipril/uso terapêutico , Tiazóis/uso terapêutico , Animais , Citosol/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Sinergismo Farmacológico , Quimioterapia Combinada , Ativação Enzimática/efeitos dos fármacos , Produtos Finais de Glicação Avançada/química , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/fisiopatologia , Lisina/análogos & derivados , Lisina/sangue , Masculino , Mitocôndrias/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteína Quinase C/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/metabolismo , Sistema Renina-Angiotensina , Superóxido Dismutase/metabolismo , Fator A de Crescimento do Endotélio Vascular/urina
9.
Mol Biol Cell ; 14(1): 1-13, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12529422

RESUMO

Telomerase is a reverse transcriptase that maintains chromosome ends. The N-terminal half of the catalytic protein subunit (TERT) contains three functional domains (I, II, and III) that are conserved among TERTs but not found in other reverse transcriptases. Guided by an amino acid sequence alignment of nine TERT proteins, mutations were introduced into yeast TERT (Est2p). In support of the proposed alignment, mutation of virtually all conserved residues resulted in loss-of-function or temperature sensitivity, accompanied by telomere shortening. Overexpression of telomerase component Est3p led to allele-specific suppression of the temperature-sensitive mutations in region I, suggesting that Est3p interacts with this protein domain. As predicted by the genetic results, a lethal mutation in region I resulted in loss of Est3p from the telomerase complex. We conclude that Est2p region I is required for the recruitment of Est3p to yeast telomerase. Given the phylogenetic conservation of region I of TERT, this protein domain may provide the equivalent function in all telomerases.


Assuntos
Proteínas Fúngicas , Proteínas/metabolismo , Telomerase/metabolismo , Leveduras/enzimologia , Sequência de Aminoácidos , Sequência Conservada , Proteínas de Ligação a DNA , Temperatura Alta , Dados de Sequência Molecular , Testes de Precipitina , Estrutura Terciária de Proteína , Proteínas de Saccharomyces cerevisiae/metabolismo , Análise de Sequência de Proteína , Leveduras/metabolismo
10.
J Appl Psychol ; 101(10): 1487-1497, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27504656

RESUMO

Organizational newcomers are unfamiliar with many aspects of their workplace and look for information to help them reduce uncertainty and better understand their new environment. One aspect critical to newcomers is the disposition of their supervisor-the person who arguably can impact the newcomer's career the most. To form an impression of their new supervisor, newcomers look to social cues from coworkers who have interpersonal contact with the supervisor. In the present research, we investigate the ways newcomers use observed ingratiation-a common impression management strategy whereby coworkers try to appear likable (Schlenker, 1980)-to form impressions of a supervisor's warmth. Research on social influence cannot easily account for how third parties will interpret ingratiation, as the behaviors linked to ingratiation suggest something positive about the target, yet the unsavory aspects of the behavior imply it may not have the same effects as other positive behaviors. Our findings suggest that newcomers are unique in that they are motivated to learn about their new supervisor, and are prone to ignore those unsavory aspects and infer something positive about a supervisor targeted with ingratiation. Our findings also suggest that this effect can be weakened based on the supervisor's response. In other words, newcomers rely less on evidence from a coworker's ingratiation in the presence of direct behaviors from the supervisor. (PsycINFO Database Record


Assuntos
Relações Interpessoais , Gestão de Recursos Humanos , Comportamento Social , Percepção Social , Local de Trabalho/psicologia , Adulto , Humanos
11.
Int J Womens Health ; 8: 131-5, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27226734

RESUMO

BACKGROUND: Obstetric anal sphincter injury (OASI) is a serious complication of vaginal births, resulting in possible long-term consequences such as incontinence and pain. Adequate detection and management of these injuries is vital in minimizing the impact they have on women. AIM: To assess the rates of detection, management, and outcomes of OASI before and after the implementation of a new clinical practice guideline and operative pro forma. MATERIALS AND METHODS: A 12-month audit of the incidence, management, and outcomes of OASI was conducted in 2009. An operative pro forma and practice guideline were implemented in 2010 followed by a further audit undertaken between 2010 and 2012. Statistical analysis was performed to determine any significant change in practice. RESULTS: The distribution of risk factors for OASI including primiparity, birthweight, and type of vaginal delivery was similar between the two audited groups. After implementation of the pro forma, the reported incidence of OASI increased from 1.62% to 3.1% (P=0.004). Significant changes in management included an increase in the use of recommended suture material (48% vs 80%, P=0.002), postoperative antibiotics (78% vs 99%, P=0.001), postoperative catheterization (52% vs 90%, P<0.001), and inpatient physiotherapy consultations (44% vs 97%, P=<0.001). An increase was seen in women attending their 6-week follow-up appointment (33% vs 54% P=0.058); however, this was just below the level of statistical significance. CONCLUSION: The introduction of the new pro forma and guideline resulted in an increase in the reported incidence of OASI, improved management, and follow-up of patients.

12.
J Appl Psychol ; 100(2): 278-94; quiz 295-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25420056

RESUMO

Although justice scholars often assume that individuals react to injustice in a manner that is distinct from their reactions to justice, few studies have examined this assumption. Indeed, the most widely utilized measures in the literature assess only the adherence to rules of justice--not their violation. We conducted 2 studies to build and test theory about differential reactions to justice and injustice. An inductive study revealed that reactions to the adherence to justice rules reflected different constructs than reactions to the violations of justice rules. In a follow-up field study, we derived hypotheses for those patterns by drawing on the negativity bias and regulatory focus literatures. Specifically, justice rule violation was predicted to be more relevant to prevention-laden outcomes that represent a high level of vigilance and concerns about safety. Justice rule adherence was predicted to be more relevant to promotion-laden outcomes that represent concerns about becoming the ideal self. The field study supported many of those predictions while showing that a full-range justice measure (i.e., one that sampled both justice rule adherence and justice rule violation) explained more variance in outcomes than existing "truncated" justice measures.


Assuntos
Comportamento Social , Justiça Social , Adulto , Feminino , Humanos , Masculino , Pesquisa Qualitativa
13.
Nat Commun ; 6: 7135, 2015 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-26011032

RESUMO

The severe geomagnetic effects of solar storms or coronal mass ejections (CMEs) are to a large degree determined by their propagation direction with respect to Earth. There is a lack of understanding of the processes that determine their non-radial propagation. Here we present a synthesis of data from seven different space missions of a fast CME, which originated in an active region near the disk centre and, hence, a significant geomagnetic impact was forecasted. However, the CME is demonstrated to be channelled during eruption into a direction +37±10° (longitude) away from its source region, leading only to minimal geomagnetic effects. In situ observations near Earth and Mars confirm the channelled CME motion, and are consistent with an ellipse shape of the CME-driven shock provided by the new Ellipse Evolution model, presented here. The results enhance our understanding of CME propagation and shape, which can help to improve space weather forecasts.

14.
J Appl Psychol ; 99(4): 599-618, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24708267

RESUMO

Although social exchange theory has become one of the most oft-evoked theories in industrial and organizational psychology, there remains no consensus about how to measure its key mechanism: social exchange relationships (Blau, 1964). Drawing on Cropanzano and Byrne's (2000) review of contemporary social exchange theorizing, we examined the content validity of perceived support, exchange quality, affective commitment, trust, and psychological contract fulfillment as indicators of social exchange relationships. We used Hinkin and Tracey's (1999) quantitative approach to content validation, which asks participants to rate the correspondence between scale items and definitions of intended (and unintended) constructs. Our results revealed that some of the most frequently utilized indicators of social exchange relationships--perceived support and exchange quality--were significantly less content valid than rarely used options like affect-based trust. Our results also revealed that 2 direct measures--Bernerth, Armenakis, Feild, Giles, and Walker's (2007) scale and a scale created for this study--were content valid. We discuss the implications of these results for future applications of social exchange theory.


Assuntos
Relações Interpessoais , Apoio Social , Confiança/psicologia , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
15.
J Appl Psychol ; 98(2): 199-236, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23458336

RESUMO

Although a flurry of meta-analyses summarized the justice literature at the turn of the millennium, interest in the topic has surged in the decade since. In particular, the past decade has witnessed the rise of social exchange theory as the dominant lens for examining reactions to justice, and the emergence of affect as a complementary lens for understanding such reactions. The purpose of this meta-analytic review was to test direct, mediating, and moderating hypotheses that were inspired by those 2 perspectives, to gauge their adequacy as theoretical guides for justice research. Drawing on a review of 493 independent samples, our findings revealed a number of insights that were not included in prior meta-analyses. With respect to social exchange theory, our results revealed that the significant relationships between justice and both task performance and citizenship behavior were mediated by indicators of social exchange quality (trust, organizational commitment, perceived organizational support, and leader-member exchange), though such mediation was not apparent for counterproductive behavior. The strength of those relationships did not vary according to whether the focus of the justice matched the target of the performance behavior, contrary to popular assumptions in the literature, or according to whether justice was referenced to a specific event or a more general entity. With respect to affect, our results showed that justice-performance relationships were mediated by positive and negative affect, with the relevant affect dimension varying across justice and performance variables. Our discussion of these findings focuses on the merit in integrating the social exchange and affect lenses in future research.


Assuntos
Afeto , Relações Interpessoais/história , Teoria Psicológica , Justiça Social/história , História do Século XXI , Humanos
16.
J Am Soc Nephrol ; 16(8): 2363-72, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15930093

RESUMO

Recent studies have identified that first-line renoprotective agents that interrupt the renin-angiotensin system not only reduce BP but also can attenuate advanced glycation end product (AGE) accumulation. This study used in vitro, preclinical, and human approaches to explore the potential effects of these agents on the modulation of the receptor for AGE (RAGE). Bovine aortic endothelial cells that were exposed to the angiotensin-converting enzyme inhibitor (ACEi) ramiprilat in the presence of high glucose demonstrated a significant increase in soluble RAGE (sRAGE) secreted into the medium. In streptozotocin-induced diabetic rats, ramipril treatment (ACEi) at 3 mg/L for 24 wk reduced the accumulation of skin collagen-linked carboxymethyllysine and pentosidine, as well as circulating and renal AGE. Renal gene upregulation of total RAGE (all three splice variants) was observed in ACEi-treated animals. There was a specific increase in the gene expression of the splice variant C-truncated RAGE (sRAGE). There were also increases in sRAGE protein identified within renal cells with ACEi treatment, which showed AGE-binding ability. This was associated with decreases in renal full-length RAGE protein from ACEi-treated rats. Decreases in plasma soluble RAGE that were significantly increased by ACEi treatment were also identified in diabetic rats. Similarly, there was a significant increase in plasma sRAGE in patients who had type 1 diabetes and were treated with the ACEi perindopril. Complexes between sRAGE and carboxymethyllysine were identified in human and rodent diabetic plasma. It is postulated that ACE inhibition reduces the accumulation of AGE in diabetes partly by increasing the production and secretion of sRAGE into plasma.


Assuntos
Nefropatias Diabéticas/metabolismo , Peptidil Dipeptidase A/metabolismo , Receptores Imunológicos/metabolismo , Processamento Alternativo , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Aorta/citologia , Arginina/análogos & derivados , Arginina/química , Western Blotting , Bovinos , Células Cultivadas , Colágeno/metabolismo , Primers do DNA/química , Nefropatias Diabéticas/sangue , Endotélio Vascular/citologia , Produtos Finais de Glicação Avançada/sangue , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Imuno-Histoquímica , Imunoprecipitação , Córtex Renal/metabolismo , Lisina/análogos & derivados , Lisina/química , Masculino , Microscopia de Fluorescência , Peso Molecular , Ramipril/análogos & derivados , Ramipril/farmacologia , Ratos , Ratos Sprague-Dawley , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Pele/metabolismo , Fatores de Tempo , Regulação para Cima
17.
Microbiology (Reading) ; 146 ( Pt 8): 2079-2089, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10931912

RESUMO

Pestalotiopsis microspora, isolate NE-32, is an endophyte of the Himalayan yew (Taxus wallichiana) that produces taxol, an important chemotherapeutic drug used in the treatment of breast and ovarian cancers. Conditions were determined to induce the perfect stage (teleomorph) of this organism in the laboratory as a critical first step to study inheritance of taxol biosynthetic genes. The perfect stage of Pestalotiopsis microspora NE-32 forms in a period of 3-6 weeks on water agarose with dried yew needles at 16-20 degrees C with 12 h of light per day. Morphological analysis of the teleomorph and sequencing of the 18S rDNA indicates that Pestalosphaeria hansenii is the perfect stage of Pestalotiopsis microspora. Only certain plants (e.g. yews, some pines, pecan, oat and some barley cultivars) allow the production of perithecia. Exhaustive methylene chloride extraction of yew (Taxus cuspidata) needles removes their capacity to induce production of perithecia. The methylene chloride extract is able to induce formation of perithecia by strain NE-32 in a bioassay system utilizing the sterilized sheaths of the Cholla cactus (Opuntia bigelovii) spine, indicating that a chemical compound(s) in yew stimulates the formation of the perfect stage. This hydrophobic plant compound(s) has been designated the perithecial-stimulating factor (PSF). The data suggest that plant products may play a role in regulating the biology of endophytic microbes.


Assuntos
Antineoplásicos Fitogênicos/biossíntese , Ascomicetos/crescimento & desenvolvimento , Ascomicetos/metabolismo , Paclitaxel/biossíntese , Ascomicetos/genética , Sequência de Bases , Primers do DNA/genética , DNA Bacteriano/genética , DNA Ribossômico/genética , Microscopia Eletrônica de Varredura , Dados de Sequência Molecular , Plantas/microbiologia , Árvores/microbiologia
18.
J Am Soc Nephrol ; 15(8): 2139-51, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15284299

RESUMO

NF-kappaB-dependent pathways play an important role in macrophage infiltration and kidney injury. NF-kappaB is regulated by angiotensin II (AII). However, the role of this pathway in diabetic nephropathy has not been clearly delineated. First, the activation of NF-kappaB, monocyte chemoattractant protein-1 (MCP-1), and macrophage infiltration in the diabetic kidney were explored, in a temporal manner. The active subunit of NF-kappaB, p65, was elevated in the diabetic animals in association with increased MCP-1 gene expression and macrophage infiltration. Second, the effects of treatment for 4 wk with the AII type 1 receptor antagonist valsartan, the AII type 2 receptor antagonist PD123319, or pyrrolidine dithiocarbamate, an inhibitor of NF-kappaB and on these parameters were assessed. These treatments were associated with a reduction in p65 activation, MCP-1 gene expression, and macrophage infiltration. These findings demonstrate a role for activation of NF-kappaB, in particular the p65 subunit, in the pathogenesis of early renal macrophage infiltration in experimental diabetes. In the context of the known proinflammatory effects of AII, it is postulated that the renoprotection conferred by angiotensin II receptor antagonism is at least partly related to the inhibition of NF-kappaB-dependent pathways.


Assuntos
Angiotensina II/metabolismo , Nefropatias Diabéticas/patologia , Macrófagos/patologia , NF-kappa B/metabolismo , Bloqueadores do Receptor Tipo 1 de Angiotensina II , Bloqueadores do Receptor Tipo 2 de Angiotensina II , Animais , Antioxidantes/farmacologia , Biomarcadores , Quimiocina CCL2/genética , Nefropatias Diabéticas/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Expressão Gênica , Proteínas I-kappa B/metabolismo , Masculino , Inibidor de NF-kappaB alfa , Subunidade p50 de NF-kappa B , Pirrolidinas/farmacologia , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , Tiocarbamatos/farmacologia , Fator de Transcrição RelA
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