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1.
J Therm Biol ; 68(Pt A): 83-88, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28689725

RESUMO

The mitochondrial basal proton leak (MBPL) significantly contributes to high body temperatures (Tb) and basal metabolic rates (BMR) in endotherms. In endotherms at a given body mass (M), liver MBPL is higher than in ectotherms, supporting the notion that MBPL may partly explain the evolutionary increase in metabolic rate (MR), fostering endothermy. Here, we re-addressed this assumption by performing a phylogenetic analysis comparing all available liver MBPL data for ecto- and endotherms. While MBPL within endotherms negatively scales with M and BMR as shown previously, MBPL of ectotherms does not scale allometrically with M. Phylogenetic analysis reveals that this result is confounded by a positive scaling coefficient for MBPL with M for reptiles. Strikingly, the reptilian MBPL reaches endothermic levels above a body mass of 6.6kg. Thus, phylogenetic scaling of MBPL supports previous claims of endotherm-like physiological characteristics in large reptiles. It appears that diversification of ancestral ectothermic tetrapods to a body mass of at least 6kg may have been required to reach a MBPL that is beneficial for sustained high body temperatures. Novel MBPL data for the lesser hedgehog tenrec, a protoendothermic eutherian that displays reptile-like thermoregulatory patterns, fall within the endo- and ectothermic allometric regressions. Finally, we add additional evidence that within endotherms, phylogenetic differences in MR do not correlate with MBPL. Collectively, these data suggest that MBPL does not universally scale with metabolic rate in ecto- or endotherms and that an increasing MBPL with M may have played an important physiological role in the evolutionary history of reptilian thermoregulation.


Assuntos
Metabolismo Basal , Filogenia , Animais , Evolução Biológica , Mitocôndrias/fisiologia , Prótons
2.
J Fish Biol ; 91(3): 723-749, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28868750

RESUMO

The anabantoids are a group of c. 137 species of air-breathing freshwater fishes found in Africa and southern Asia. All anabantoids have a pair of suprabranchial chambers that each house an air-breathing organ known as the labyrinth apparatus: a complex bony structure lined with thin, highly vascularised respiratory epithelium. The labyrinth apparatus allows anabantoids to extract oxygen from air and is a morpho-physiological innovation that has had a dramatic influence on the behaviour of these fishes. Air-breathing influences a wide range of anabantoid behaviours, including territorial displays, courtship and breeding and parental care and also equips these fishes to persist in hypoxic and polluted water. These traits also make anabantoids successful invaders of novel habitats, a global problem compounded by their popularity in the aquarium trade. By reviewing the functionality and evolution of air breathing in anabantoids, this review aims to examine the role of the labyrinth apparatus in modulating behaviour within this group. The anabantoids are a fascinating group and have often been cited as a model organism due to the stereotypical and easily identifiable behaviours that they adopt during social interactions. They also provide a unique opportunity to further our understanding about how fishes adapt their behaviour in response to an extreme environment, whilst limited by their own physiological constraints.


Assuntos
Agressão , Peixes/fisiologia , Comportamento Sexual Animal , África , Animais , Ásia , Ecossistema , Hipóxia , Oxigênio/metabolismo , Fenótipo , Reprodução
3.
J Evol Biol ; 26(7): 1588-97, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23662792

RESUMO

The regulation of insect respiratory gas exchange has long been an area of interest. In particular, the reason why insects from at least five orders exhibit patterns of gas exchange that include regular periods of spiracular closure has been the source of much controversy. Three adaptive hypotheses propose that these discontinuous gas-exchange cycles (DGCs) evolved to either limit water loss across respiratory surfaces, facilitate gas exchange in underground environments or to limit oxidative damage. It is possible that DGCs evolved independently multiple times and for different reasons, but for DGCs to be a plausible target for natural selection, they must be heritable and confer a fitness benefit. In a previous study of cockroaches Nauphoeta cinerea, we demonstrated that DGCs are repeatable and extend survival under food and water restriction. Here, we show for the first time that DGCs are heritable, suggesting that they are a plausible target for natural selection.


Assuntos
Baratas/fisiologia , Herança Multifatorial , Fenômenos Fisiológicos Respiratórios , Animais , Dióxido de Carbono/análise , Baratas/genética , Feminino , Masculino , Fenótipo
4.
J Exp Biol ; 216(Pt 9): 1726-35, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23348943

RESUMO

The field metabolic rate (FMR) of a free-ranging animal can be considered as the sum of its maintenance costs (minimum metabolic rate, MMR) and additional costs associated with thermoregulation, digestion, production and activity. However, the relationships between FMR and BMR and how they relate to behaviour and extrinsic influences is not clear. In seabirds, FMR has been shown to increase during the breeding season. This is presumed to be the result of an increase in foraging activity, stimulated by increased food demands from growing chicks, but few studies have investigated in detail the factors that underlie these increases. We studied free-ranging Australasian gannets (Morus serrator) throughout their 5 month breeding season, and evaluated FMR, MMR and activity-related metabolic costs on a daily basis using the heart rate method. In addition, we simultaneously recorded behaviour (flying and diving) in the same individuals. FMR increased steadily throughout the breeding season, increasing by 11% from the incubation period to the long chick-brooding period. However, this was not accompanied by either an increase in flying or diving behaviour, or an increase in the energetic costs of activity. Instead, the changes in FMR could be explained exclusively by a progressive increase in MMR. Seasonal changes in MMR could be due to a change in body composition or a decrease in body condition associated with changing the allocation of resources between provisioning adults and growing chicks. Our study highlights the importance of measuring physiological parameters continuously in free-ranging animals in order to understand fully the mechanisms underpinning seasonal changes in physiology and behaviour.


Assuntos
Metabolismo Basal/fisiologia , Aves/fisiologia , Cruzamento , Animais , Austrália , Calibragem , Ritmo Circadiano/fisiologia , Voo Animal/fisiologia , Frequência Cardíaca/fisiologia , Consumo de Oxigênio/fisiologia , Análise de Regressão , Estações do Ano , Fatores de Tempo
5.
Proc Biol Sci ; 279(1726): 185-93, 2012 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-21632624

RESUMO

Metabolic rates of mammals presumably increased during the evolution of endothermy, but molecular and cellular mechanisms underlying basal metabolic rate (BMR) are still not understood. It has been established that mitochondrial basal proton leak contributes significantly to BMR. Comparative studies among a diversity of eutherian mammals showed that BMR correlates with body mass and proton leak. Here, we studied BMR and mitochondrial basal proton leak in liver of various marsupial species. Surprisingly, we found that the mitochondrial proton leak was greater in marsupials than in eutherians, although marsupials have lower BMRs. To verify our finding, we kept similar-sized individuals of a marsupial opossum (Monodelphis domestica) and a eutherian rodent (Mesocricetus auratus) species under identical conditions, and directly compared BMR and basal proton leak. We confirmed an approximately 40 per cent lower mass specific BMR in the opossum although its proton leak was significantly higher (approx. 60%). We demonstrate that the increase in BMR during eutherian evolution is not based on a general increase in the mitochondrial proton leak, although there is a similar allometric relationship of proton leak and BMR within mammalian groups. The difference in proton leak between endothermic groups may assist in elucidating distinct metabolic and habitat requirements that have evolved during mammalian divergence.


Assuntos
Metabolismo Basal , Marsupiais/metabolismo , Mesocricetus/metabolismo , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Musculares/metabolismo , Prótons , Animais , Peso Corporal , Respiração Celular , Cricetinae , Eletrodos , Fígado/metabolismo , Músculo Esquelético/metabolismo , Oniocompostos/química , Oxigênio/química , Filogenia , Queensland , Análise de Regressão , Especificidade da Espécie , Compostos de Tritil/química
6.
J Hum Evol ; 63(5): 718-22, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22963931

RESUMO

Debates about the evolution of human bipedality sometimes include discussion on the energy costs of terrestrial locomotion of extinct and extant hominins. However, comparative analyses of hominin transport costs conducted to date have been limited and potentially misinforming, in part because they fail to consider phylogenetic history. In the present study, we compare the measured costs of pedestrian locomotion in humans and the estimated costs for Australopithecus afarensis (an early bipedal hominin), to a database of locomotory costs for mammals. Using data for 81 species of mammal, we demonstrate significant phylogenetic signal in both log-transformed body mass (logMass) and log-transformed net cost of transport (logNCOT), but no phylogenetic signal in residuals of the relationship between logNCOT and logMass. We then used this relationship to generate a prediction line for NCOT based on body mass, and compared this prediction with published measured data for NCOT of running and walking in humans, and estimated NCOT of walking in A. afarensis. The cost of human walking was 25% lower than predicted, while the cost of running was 27% higher. The cost of A. afarensis walking was 32% lower than predicted. However, all of these data points fall within the 95% prediction interval for mammals, indicating that they are not significantly lower or higher than predicted for other mammals of similar mass. Moreover, the difference between humans and our closest living relative the common chimpanzee is comparable to differences between other similarly closely related species. We therefore conclude that there is no evidence from metabolic data that humans, or A. afarensis, have/had a reduced energy cost of pedestrian locomotion compared to other mammals in general.


Assuntos
Hominidae/fisiologia , Caminhada/fisiologia , Animais , Metabolismo Energético/fisiologia , Hominidae/metabolismo , Humanos , Consumo de Oxigênio/fisiologia , Pan troglodytes
7.
BJOG ; 119(7): 857-65, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22530937

RESUMO

OBJECTIVE: To compare six validation criteria for umbilical cord blood gas (UCBG) values in vigorous and nonvigorous neonates. DESIGN: Retrospective cohort study. SETTING: Single tertiary obstetric centre, King Edward Memorial Hospital (KEMH), Perth, Western Australia. SAMPLE: A total of 37,763 consecutive deliveries at >23 weeks of gestation. METHODS: Six validation criteria were compared to evaluate the proportion of deliveries with 'valid' UCBG data; and the proportion of vigorous and nonvigorous neonates with metabolic acidaemia. MAIN OUTCOMES: Proportion of deliveries with 'valid' UCBG values; proportions of vigorous and nonvigorous neonates with normal, borderline and abnormal UCBG values. RESULTS: The criteria based on KEMH 5th centile arteriovenous pH and Pco(2) differences resulted in a higher proportion of neonates with 'valid' UCBG values than the previously described Westgate and Kro criteria. The increase in 'valid' UCBG values occurred across the entire study population including vigorous and nonvigorous neonates. Among neonates with short-term neonatal complications there was an increase in nonvigorous neonates with umbilical artery metabolic acidaemia. There was no corresponding increase in vigorous neonates diagnosed with abnormal UCBG values. CONCLUSIONS: Use of the KEMH criteria results in an increase in the proportion of nonvigorous term neonates with UCBG data considered 'valid' to aid clinicians in the management of the neonate shortly after delivery. This change occurs without increasing the rate of false-positive diagnoses of acidaemia in vigorous neonates. The KEMH 'validation' criteria were developed from an entire presenting population and provide a simple algorithm that can be universally applied to identify neonates with nonphysiological UCBG values.


Assuntos
Acidose/diagnóstico , Técnicas de Apoio para a Decisão , Sangue Fetal/fisiologia , Acidose/sangue , Algoritmos , Índice de Apgar , Gasometria , Estudos de Coortes , Humanos , Concentração de Íons de Hidrogênio , Recém-Nascido , Reprodutibilidade dos Testes , Estudos Retrospectivos , Artérias Umbilicais , Veias Umbilicais
8.
J Clin Invest ; 108(12): 1759-70, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11748259

RESUMO

Nitrotyrosine formation is a hallmark of vascular inflammation, with polymorphonuclear neutrophil-derived (PMN-derived) and monocyte-derived myeloperoxidase (MPO) being shown to catalyze this posttranslational protein modification via oxidation of nitrite (NO(2)(-)) to nitrogen dioxide (NO(2)(*)). Herein, we show that MPO concentrates in the subendothelial matrix of vascular tissues by a transcytotic mechanism and serves as a catalyst of ECM protein tyrosine nitration. Purified MPO and MPO released by intraluminal degranulation of activated human PMNs avidly bound to aortic endothelial cell glycosaminoglycans in both cell monolayer and isolated vessel models. Cell-bound MPO rapidly transcytosed intact endothelium and colocalized abluminally with the ECM protein fibronectin. In the presence of the substrates hydrogen peroxide (H(2)O(2)) and NO(2)(-), cell and vessel wall-associated MPO catalyzed nitration of ECM protein tyrosine residues, with fibronectin identified as a major target protein. Both heparin and the low-molecular weight heparin enoxaparin significantly inhibited MPO binding and protein nitrotyrosine (NO(2)Tyr) formation in both cultured endothelial cells and rat aortic tissues. MPO(-/-) mice treated with intraperitoneal zymosan had lower hepatic NO(2)Tyr/tyrosine ratios than did zymosan-treated wild-type mice. These data indicate that MPO significantly contributes to NO(2)Tyr formation in vivo. Moreover, transcytosis of MPO, occurring independently of leukocyte emigration, confers specificity to nitration of vascular matrix proteins.


Assuntos
Endotélio Vascular/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Peroxidase/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismo , Animais , Transporte Biológico , Degranulação Celular , Glicosaminoglicanos/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/fisiologia , Dióxido de Nitrogênio/metabolismo , Coelhos , Ratos
9.
Cancer Lett ; 254(1): 146-55, 2007 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-17451874

RESUMO

The mechanism by which the HMGA protein p8 facilitates tumorigenesis may be cell cycle dysregulation. Control- (C) LbetaT2 cells, which express p8, form tumors at a rate five-times faster than p8-knockdown (p8-KD)-LbetaT2 cells. In association with this heightened tumorigenic potential, p8-expressing C-LbetaT2 cells avoid G(0)/G(1) arrest and become genetically unstable while p8-KD-LbetaT2 cells arrest in G(0)/G(1), become senescent upon overgrowth, and maintain a diploid population. These phenotypic changes correspond to altered cell cycle regulation at the G(1)-to-S transition that may be due to p8-mediated changes in expression of the Cip/Kip family members of cell cycle inhibitors, p21, p27, and p57.


Assuntos
Ciclo Celular/genética , Proteínas de Ligação a DNA/genética , Proteínas de Neoplasias/genética , Neoplasias Experimentais/patologia , Animais , Western Blotting , Ciclo Celular/fisiologia , Linhagem Celular Transformada , Proliferação de Células , Senescência Celular/genética , Senescência Celular/fisiologia , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Inibidor de Quinase Dependente de Ciclina p57/genética , Inibidor de Quinase Dependente de Ciclina p57/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fase G1/genética , Fase G1/fisiologia , Expressão Gênica , Proteínas HMGA/genética , Proteínas HMGA/metabolismo , Camundongos , Camundongos Nus , Mutação , Proteínas de Neoplasias/metabolismo , Neoplasias Experimentais/genética , Neoplasias Experimentais/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Fase de Repouso do Ciclo Celular/genética , Fase de Repouso do Ciclo Celular/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , beta-Galactosidase/metabolismo
10.
Anim Reprod Sci ; 100(1-2): 216-22, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17023125

RESUMO

The southern hairy-nosed wombat (Lasiorhinus latifrons) is a seasonal breeding, burrowing marsupial adapted to a semi-arid environment and the closest relative of the endangered northern hairy-nosed wombat (Lasiorhinus krefftii). Females typically give birth to one to two young every 3 years with young weaned at 360-400 days. This study examined the occurrence of polyoestry in a wild population of southern hairy-nosed wombats, and in particular the ability of this species to produce additional offspring in the same breeding season if a young was prematurely lost or removed. Pouch young were removed during the breeding seasons of 1996/1997 and 2003. No females from the 1996 (n=3)/1997 (n=3) group gave birth to a second pouch young in the same breeding season. However, two females in this group gave birth to young the following season. In contrast, all the 2003 group of females (n=6) produced a second offspring in the same breeding season after removal of pouch young (RPY). The reason for the different response to RPY between the two groups is unknown. These studies confirm that southern hairy-nosed wombats are polyoestrus in the wild and are capable of producing more than one offspring in a single breeding season. Females that failed to return to oestrus in the breeding season that pouch young were removed bred again in the following season. Rapid replacement of southern hairy-nosed wombat pouch young in the same breeding season as RPY suggests that this procedure, linked to either hand-rearing or interspecific cross-fostering, should be seriously considered as a priority conservation action to increase the population size of the critically endangered sister species, the northern hairy-nosed wombat.


Assuntos
Ciclo Estral/fisiologia , Marsupiais/fisiologia , Animais , Feminino
11.
Sci Total Environ ; 565: 1124-1137, 2016 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-27261427

RESUMO

After almost fifteen years of successful waste disposal operations, the first unambiguous airborne radiation release from the Waste Isolation Pilot Plant (WIPP) was detected beyond the site boundary on February 14, 2014. It was the first accident of its kind in the 15-year operating history of the WIPP. The accident released moderate levels of radioactivity into the underground air. A small but measurable amount of radioactivity also escaped to the surface through the ventilation system and was detected above ground. The dominant radionuclides released were americium and plutonium, in a ratio consistent with the known content of a breached drum. The radiation release was caused by a runaway chemical reaction inside a transuranic (TRU) waste drum which experienced a seal and lid failure, spewing radioactive materials into the repository. According to source-term estimation, approximately 2 to 10Ci of radioactivity was released from the breached drum into the underground, and an undetermined fraction of that source term became airborne, setting off an alarm and triggering the closure of seals designed to force exhausting air through a system of filters including high-efficiency-particulate-air (HEPA) filters. Air monitoring across the WIPP site intensified following the first reports of radiation detection underground to determine the extent of impact to WIPP personnel, the public, and the environment, if any. This article attempts to compile and interpret analytical data collected by an independent monitoring program conducted by the Carlsbad Environmental Monitoring & Research Center (CEMRC) and by a compliance-monitoring program conducted by the WIPP's management and operating contractor, the Nuclear Waste Partnership (NWP), LLC., in response to the accident. Both the independent and the WIPP monitoring efforts concluded that the levels detected were very low and localized, and no radiation-related health effects among local workers or the public would be expected.


Assuntos
Poluentes Radioativos do Ar/análise , Resíduos Radioativos/análise , Radioisótopos/análise , Amerício/análise , New Mexico , Plutônio/análise , Monitoramento de Radiação
12.
Biochim Biophys Acta ; 1411(2-3): 385-400, 1999 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-10320671

RESUMO

Nitric oxide (NO) plays an important role as a cell-signalling molecule, anti-infective agent and, as most recently recognised, an antioxidant. The metabolic fate of NO gives rise to a further series of compounds, collectively known as the reactive nitrogen species (RNS), which possess their own unique characteristics. In this review we discuss this emerging aspect of the NO field in the context of the formation of the RNS and what is known about their effects on biological systems. While much of the insight into the RNS has been gained from the extensive chemical characterisation of these species, to reveal biological consequences this approach must be complemented by direct measures of physiological function. Although we do not know the consequences of many of the dominant chemical reactions of RNS an intriguing aspect is now emerging. This review will illustrate how, when specificity and amplification through cell signalling mechanisms are taken into account, the less significant reactions, in terms of yield or rates, can explain many of the biological responses of exposure of cells or physiological systems to RNS.


Assuntos
Óxido Nítrico/fisiologia , Animais , Apoptose , Inflamação/fisiopatologia , Lipoproteínas/metabolismo , Membranas/metabolismo , Nitratos/metabolismo , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/química , Nitrogênio/fisiologia , Oxirredução , Transdução de Sinais , Tirosina/análogos & derivados , Tirosina/metabolismo , Vasodilatação
13.
Circulation ; 103(20): 2508-13, 2001 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-11369693

RESUMO

BACKGROUND: The effect of temporal and spatial gradients in shear on primary human endothelial cell (HUVEC) proliferation was investigated. The sudden-expansion flow chamber (SEFC) model was used to differentiate the effect of temporal gradients in shear from that of spatial gradients. With a sudden onset of flow, cells are exposed to both temporal and spatial gradients of shear. The temporal gradients can be eliminated by slowly ramping up the flow. METHODS AND RESULTS: HUVEC proliferation in the SEFC remained unstimulated when the onset of flow was slowly ramped. Sudden onset of flow stimulated a 105% increase of HUVEC proliferation (relative to ramped onset) within the region of flow reattachment. To further separate temporal and spatial gradients, a conventional parallel-plate flow chamber was used. A single 0.5-second impulse of 10 dyne/cm(2) increased HUVEC proliferation 54+/-3% relative to control. When flow was slowly ramped over 30 seconds, HUVEC proliferation was not significantly different from controls. Steady laminar shear over 20 minutes inhibited HUVEC proliferation relative to controls regardless of step (36+/-8%) or ramp (21+/-5%) onsets of flow. CONCLUSIONS: The results indicate that temporal gradients in shear stress stimulate endothelial cell proliferation, whereas spatial gradients affect endothelial proliferation no differently than steady uniform shear stress.


Assuntos
Divisão Celular , Endotélio Vascular/citologia , Células Cultivadas , Humanos , Modelos Teóricos , Estresse Mecânico , Fatores de Tempo
14.
Methods Enzymol ; 396: 553-68, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16291262

RESUMO

Results from vessel bioassays have provided the foundation for much of our understanding of the mechanisms that control vascular homeostasis and blood flow. The seminal observations that led to the discovery that nitric oxide (NO) is a critical mediator of vascular relaxation were made with the use of such methodology, and many studies have used NO-dependent vessel relaxation as an experimental readout for understanding mechanisms that regulate vascular NO function. Studies have coupled controlling oxygen tensions within vessel bioassay chambers to begin to understand how oxygen-specifically hypoxia-regulate NO function, and this context has identified red cells-specifically hemoglobin within-as critical modulators. Alone, vessel bioassays or measuring oxygen partial pressures (pO2) is relatively straightforward, but the combination necessitates consideration of several factors. We use the example of deoxygenated red cells/hemoglobin-dependent potentiation of nitrite-dependent dilation to illustrate the salient factors that are critical to consider in designing and interpreting experiments aimed at understanding the interplay between oxygen and NO function in the vasculature.


Assuntos
Óxido Nítrico/fisiologia , Oxigênio/metabolismo , Vasodilatação/fisiologia , Eritrócitos/metabolismo , Hemólise , Humanos , Pressão
15.
Mol Endocrinol ; 15(2): 281-93, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11158334

RESUMO

Human tissues that express the angiotensin II (Ang II) type 1 receptor (hAT(1)R) can synthesize four distinct alternatively spliced hAT(1)R mRNA transcripts. In this study, we show that the relative abundance of these mRNA transcripts varies widely in human tissues, suggesting that each splice variant is functionally distinct. Here we demonstrate, for the first time, that the hAT(1)R-B mRNA splice variant encodes a novel long hAT(1)R isoform in vivo that has significantly diminished affinity for Ang II (i.e. >3-fold) when compared with the short hAT(1)R isoform (encoded by hAT(1)R-A mRNA splice variant). This reduced agonist affinity caused a significant shift to the right in the dose-response curve for Ang II-induced inositol trisphosphate production and Ca(2+) mobilization of the long hAT(1)R when compared with that of the short hAT(1)R. The functional differences between these isoforms allows Ang II responsiveness to be fine-tuned by regulating the relative abundance of the long and short hAT(1)R isoform expressed in a given human tissue.


Assuntos
Processamento Alternativo , RNA Mensageiro/análise , Receptores de Angiotensina/genética , Receptores de Angiotensina/fisiologia , Neoplasias do Córtex Suprarrenal/metabolismo , Sequência de Aminoácidos , Angiotensina II/farmacologia , Animais , Sequência de Bases , Células CHO , Cricetinae , Éxons , Citometria de Fluxo , Expressão Gênica , Glicosilação , Humanos , Fosfatos de Inositol/biossíntese , Cinética , Dados de Sequência Molecular , RNA Mensageiro/biossíntese , Receptor Tipo 1 de Angiotensina , Receptor Tipo 2 de Angiotensina , Receptores de Angiotensina/química , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Relação Estrutura-Atividade , Distribuição Tecidual , Transfecção , Células Tumorais Cultivadas
16.
Trends Cardiovasc Med ; 7(3): 94-100, 1997 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21235871

RESUMO

Cardiovascular disease is rare in premenopausal women compared with men in similar age groups. After menopause, however, the gender difference in cardiovascular disease diminishes, and there is an increased incidence of coronary risk and events in women. Although a number of factors contribute to the development of atherosclerotic disease in women, estrogen replacement therapy reduces cardiovascular risk. Potential molecular mechanisms for the antiatherosclerotic effects of estrogen are discussed here. It is proposed that lipid-lowering and antioxidant properties of estrogen synergize to elicit the observed vasoprotective effects. These processes are discussed in the context of balloon-injury models and hypercholesterolemia. (Trends Cardiovasc Med 1997;7:94-100). © 1997, Elsevier Science Inc.

17.
Cardiovasc Res ; 24(12): 953-8, 1990 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2097061

RESUMO

STUDY OBJECTIVE: The aim was to study contractile responses of segments of rat arteries taken from pressure loaded and pressure protected regions and to examine the role of endothelial derived factors on the spontaneous activity of pressure loaded ring segments. DESIGN: Rats were subjected to complete aortic coarctation between the origins of the renal arteries and allowed to recover for 8 d. After 8 d arterial pressures were measured in awake animals from the pressure loaded and pressure protected regions simultaneously. Ring segments (2-3 mm) were taken from the two regions and mounted in a tissue bath for isometric force measurements. Similar studies were conducted in sham animals and in animals in which the kidney distal to the coarctation had been removed. EXPERIMENTAL MATERIAL: Female Sprague-Dawley rats, weight 200-250 g, were used. MEASUREMENTS AND MAIN RESULTS: Eight days after coarctation mean aortic pressure proximal to the occlusion was 168(SEM 1.29) mm Hg (n = 104) while distally it was 38(2.42) (n = 40). Of the rings tested 96% showed spontaneous rhythmic activity, having a mean frequency of 3.94(0.17) cycles.min-1. Spontaneous activity was not present in the pressure protected segments taken from the same animals. Rats with the distal kidney removed (n = 25) failed to become hypertensive and similarly prepared ring segments failed to show spontaneous rhythmic activity. Prior removal of the endothelial layer had no effect on the spontaneous contractile responses in pressure loaded segments. Histological examination showed that the media to lumen ratio was increased in coarcted rats in both pressure loaded and pressure protected regions compared to similar regions in sham operated animals. CONCLUSIONS: Pressure loaded arterial segments show spontaneous contractile activity when compared to sham segments by mechanisms not dependent on endothelial derived factors. The increase in pressure proximal to the occlusion is dependent on the renin-angiotensin system, since pressure was not increased when the distal kidney was removed. We hypothesise that the chronic pressure load induces fundamental changes in membrane permeability which leads to spontaneous contractile activity.


Assuntos
Contração Muscular/fisiologia , Músculo Liso Vascular/fisiologia , Acetilcolina/farmacologia , Animais , Aorta Torácica/anatomia & histologia , Pressão Sanguínea/fisiologia , Endotélio Vascular/fisiologia , Feminino , Técnicas In Vitro , Ligadura , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/anatomia & histologia , Prazosina/farmacologia , Ratos , Ratos Endogâmicos , Artéria Renal/anatomia & histologia
18.
Hypertension ; 35(1 Pt 2): 403-8, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10642332

RESUMO

Zucker rats are a useful model in which to define the mechanisms that link obesity to diabetes and associated cardiovascular disease. The present study tests the hypothesis that diabetic obese (compared with nondiabetic lean) Zucker rats are hypertensive and display a further increase in arterial pressure when fed a high salt diet. Male, nondiabetic lean and diabetic obese Zucker rats were chronically instrumented with telemetry probes and fed a basal salt diet for 3 weeks followed by exposure to a high salt diet for 11 days. On the basal diet, obese (vs lean) rats had significantly higher arterial pressures ( approximately 13 mm Hg), and the high salt diet significantly elevated mean arterial pressure (MAP) in obese (but not lean) Zucker rats ( approximately 12 mm Hg). Blockade of the sympathetic nervous system with hexamethonium caused a significantly larger decrease in MAP in obese (vs lean) Zucker rats fed the basal diet (51 vs 33 mm Hg), but the high salt diet did not increase the hexamethonium-induced reduction in arterial pressure in obese rats. Acute blockade of angiotensin receptors with losartan resulted in similar decreases in MAP in both groups on either diet. Acetylcholine-induced vasodilatory capacity of the carotid artery was significantly less in the obese (vs lean) Zucker rats. Together these data indicate that increased sympathetic nervous system activity and decreased vascular reactivity may contribute to elevated arterial pressure in type 2 diabetic, obese Zucker rats, but the sympathetic nervous system does not appear to contribute to the dietary salt-sensitive hypertension in this model.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus/fisiopatologia , Hipertensão/fisiopatologia , Obesidade , Cloreto de Sódio na Dieta/farmacologia , Sistema Nervoso Simpático/fisiopatologia , Angiotensina II/fisiologia , Antagonistas de Receptores de Angiotensina , Animais , Anti-Hipertensivos/farmacologia , Glicemia , Pressão Sanguínea/efeitos dos fármacos , Artérias Carótidas/inervação , Artérias Carótidas/fisiologia , Ritmo Circadiano/fisiologia , Bloqueadores Ganglionares/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Hexametônio/farmacologia , Hipertensão/tratamento farmacológico , Losartan/farmacologia , Masculino , Ratos , Ratos Zucker , Receptor Tipo 1 de Angiotensina , Receptor Tipo 2 de Angiotensina , Sistema Renina-Angiotensina/fisiologia , Sistema Nervoso Simpático/efeitos dos fármacos , Vasoconstrição/fisiologia
19.
Am J Surg Pathol ; 12(2): 83-95, 1988 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-3257655

RESUMO

Granulomatous mycosis fungoides is an unusual histologic variant of mycosis fungoides, a condition that is ordinarily indolent. Granulomatous slack skin, like granulomatous mycosis fungoides, shows epidermotropism, granulomatous inflammation, a clonal T-helper cell population, and progression to systemic lymphoma in some cases. Unlike granulomatous mycosis fungoides, it is characterized clinically by bulky, pendulous skin folds. The similarities between the two conditions prompted us to compare the histologic features. We reviewed 24 biopsies from 10 patients with granulomatous mycosis fungoides. These showed several distinct histologic patterns, including three cases that mimicked granuloma annulare. We also reviewed biopsy specimens from four patients with granulomatous slack skin. These specimens had a more stereotypic appearance, with permeation of the entire dermis and subcutis by lymphocytes, marked epidermotropism, and a more even distribution of granulomas and giant cells within the infiltrate. Biopsies of fully developed lesions of granulomatous slack skin showed elastolysis involving the full thickness of the dermis--a feature not seen in any of our granulomatous mycosis fungoides cases. Biopsy specimens from granulomatous mycosis fungoides and granulomatous slack skin may be mistaken for nonneoplastic granulomatous dermatitides, but they can usually be distinguished from these by the presence of epidermotropism or atypical lymphocytes. Because several of our patients with granulomatous mycosis fungoides died after courses of unremarkable length, it seems unlikely that the presence of granulomas is invariably correlated with a more benign course than nongranulomatous mycosis fungoides.


Assuntos
Granuloma/patologia , Linfoma/patologia , Micose Fungoide/patologia , Dermatopatias/patologia , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Biópsia , Feminino , Humanos , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Pele/patologia , Linfócitos T
20.
Pediatrics ; 85(2): 210-4, 1990 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2296509

RESUMO

The possibility of transmission of the human immunodeficiency virus (HIV) from infected children to their contacts has been confronted in households, schools, day-care centers, and other child care settings. Cases reported to the Centers for Disease Control and several studies of close contacts of HIV-infected patients suggested that the risk of transmission in these settings is extremely low. However, most of these studies involved infected adults or older children. Younger children, who drool, bite, mouth toys, and are incontinent, may be more likely to transmit HIV in these settings. To assess this possibility, the authors tested 89 members of households in which 25 children with HIV infection, most of whom were preschool-aged, resided. Household members had close personal contact with the infected children. They shared many items likely to be soiled with blood and body fluids, such as toys, toothbrushes, eating utensils, toilets, and bathtubs. Hugging, kissing, sharing a bed, and bathing together were common. Household members were tested no sooner than 4 months after initial contact with the infected child, to allow adequate time for sero-conversion. All 89 participating household members were anti-HIV seronegative, and 78 who were tested were serum p24 antigen negative. It was concluded from this study and other evidence that the risk of transmission from children to their contacts is extremely low and has not been clearly documented in the household setting.


Assuntos
Síndrome da Imunodeficiência Adquirida/transmissão , Família , Adolescente , Criança , Características da Família , Feminino , Soropositividade para HIV , Utensílios Domésticos , Humanos , Lactente , Masculino , Fatores de Risco , Fatores de Tempo
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