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1.
Indoor Air ; 24(5): 511-20, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24417591

RESUMO

This article aims at evaluating indoor noise levels at home and investigating the factors that may influence their variability. An 8-day noise measurement campaign was conducted in the homes of 44 schoolchildren attending the public primary schools of Besançon (France). The presence of the inhabitants in the dwelling and the noisy events occurring indoors and outdoors was daily collected using a time-location-activity diary (TLAD); 902 time periods were analyzed. The indoor noise level increased significantly with the outdoor noise level, along with the duration of the presence or level of activity of the inhabitants at home. However, this effect may vary according to the period of day and the day of the week. Moreover, a significant part of the day and evening indoor noise level variability was explained when considering the TLAD variables: 46% and 45% in the bedroom, 54% and 39% in the main room, respectively. Our results highlight the complexity of the indoor environment in the dwellings of children living in an urban area. Combining the inhabitant presence and indoor noise source descriptors with outdoor noise levels and other dwelling or inhabitant characteristics could improve large-scale epidemiological studies. However, additional efforts are still needed, particularly during the night period.


Assuntos
Habitação/estatística & dados numéricos , Ruído , Criança , Cidades , Família , Humanos , População Urbana
2.
Mol Ecol ; 22(2): 450-62, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23190431

RESUMO

Loci considered to be under selection are generally avoided in attempts to infer past demographic processes as they do not fit neutral model assumptions. However, opportunities to better reconstruct some aspects of past demography might thus be missed. Here we examined genetic differentiation between two sympatric European oak species with contrasting ecological dynamics (Quercus robur and Quercus petraea) with both outlier (i.e. loci possibly affected by divergent selection between species or by hitchhiking effects with genomic regions under selection) and nonoutlier loci. We sampled 855 individuals in six mixed forests in France and genotyped them with a set of 262 SNPs enriched with markers showing high interspecific differentiation, resulting in accurate species delimitation. We identified between 13 and 74 interspecific outlier loci, depending on the coalescent simulation models and parameters used. Greater genetic diversity was predicted in Q. petraea (a late-successional species) than in Q. robur (an early successional species) as introgression should theoretically occur predominantly from the resident species to the invading species. Remarkably, this prediction was verified with outlier loci but not with nonoutlier loci. We suggest that the lower effective interspecific gene flow at loci showing high interspecific divergence has better preserved the signal of past asymmetric introgression towards Q. petraea caused by the species' contrasting dynamics. Using markers under selection to reconstruct past demographic processes could therefore have broader potential than generally recognized.


Assuntos
Fluxo Gênico , Loci Gênicos , Quercus/genética , DNA de Plantas/genética , França , Marcadores Genéticos , Variação Genética , Genótipo , Funções Verossimilhança , Polimorfismo de Nucleotídeo Único , Simpatria
3.
Heredity (Edinb) ; 109(6): 361-71, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22990311

RESUMO

Genome scans are increasingly used to study ecological speciation, providing a useful genome-wide perspective on divergent selection in the presence of gene flow. Here, we compare current approaches to detect footprints of divergent selection in closely related species. We analyzed 192 individuals from two interfertile European temperate oak species using 30 nuclear microsatellites from eight linkage groups. These markers present little intraspecific differentiation and can be used in combination to assign individual genotypes to species. We first show that different outlier detection tests give somewhat different results, possibly due to model constraints. Second, using linkage information for these markers, we further characterize the signature of divergent selection in the presence of gene flow. In particular, we show that recombination estimates for regions with outlier markers are lower than those for a control region, in line with a prediction from ecological speciation theory. Most importantly, we show that analyses at the haplotype level can distinguish between truly divergent (bi-directional) selection and positive selection in one of the two species, offering a new and improved method for characterizing the speciation process.


Assuntos
Especiação Genética , Repetições de Microssatélites/genética , Quercus/genética , Seleção Genética , Evolução Molecular , Fluxo Gênico , Variação Genética , Genética Populacional , Genoma de Planta , Haplótipos
4.
Mol Ecol ; 18(10): 2228-42, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19302359

RESUMO

Successful hybridisation and subsequent introgression lead to the transfer of genetic material across species boundaries. In this process, species relative abundance can play a significant role. If one species is less abundant than the other, its females will receive many heterospecific gametes, increasing mate-recognition errors and thus hybridisation rate. Moreover, first-generation hybrids will also more likely mate with the more abundant species, leading to asymmetric introgression. These predictions have important fundamental consequences, especially during biological invasions or when a rare species threatened by extinction is surrounded by individuals from a related species. However, experimental tests in nature of the importance of the relative abundance of each species on hybridisation dynamics remain scarce. We assess here the impact of species relative abundance on hybridisation dynamics among four species from the European white oak species complex. A total of 2107 oak trees were genotyped at 10 microsatellite markers and Bayesian clustering methods were used to identify reference trees of each species. We then used these reference trees to simulate purebred and hybrid genotypes to determine optimal threshold for genetic assignment. With this approach, we found widespread evidence of hybridisation between all studied oak species, with high occurrence of hybrids, varying from 11% to 31% according to stand and sampling strategies. This finding suggests that hybridisation is a common phenomenon that plays a significant role in evolution of this oak species complex. In addition, we demonstrate a strong impact of species abundance on both hybridisation rate and introgression directionality.


Assuntos
Evolução Molecular , Genética Populacional , Hibridização Genética , Quercus/genética , Teorema de Bayes , Análise por Conglomerados , DNA de Plantas/genética , Genótipo , Repetições de Microssatélites , Modelos Genéticos , Análise de Sequência de DNA , Especificidade da Espécie
5.
Heredity (Edinb) ; 102(5): 442-52, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19240752

RESUMO

Powerful and accurate detection of first-generation (F1) hybrids and backcrosses in nature is needed to achieve a better understanding of the function and dynamics of introgression. To document the frequency of ongoing interspecific gene exchange between two Mediterranean evergreen oaks, the cork oak (Quercus suber) and the holm oak (Q. ilex), we analyzed 1487 individuals originating from across the range of the two species using eight microsatellite loci and two Bayesian clustering approaches (implemented in the programs STRUCTURE and NEWHYBRIDS). Simulated data were used to assess the differences between the two clustering methods and to back up the choice of the threshold value for the posterior probability to discriminate admixed from pure individuals. We found that the use of STRUCTURE resulted in the highest power to detect hybrids, whereas NEWHYBRIDS provided the highest accuracy. Irrespective of the approach, the two species were clearly distinguished as independent genetic entities without any prior information. In contrast with previous reports, we found no evidence for unidirectional introgression. The overall hybridization rate was very low (<2% of introgressed individuals). Only two individuals were identified as F1 hybrids and five as early backcrosses. This work shows that the combined application of the two complementary Bayesian approaches and their systematic validation with simulations, fit for the case at hand, helps gain resolution in the identification of admixed individuals.


Assuntos
Hibridização Genética , Quercus/genética , Repetições de Microssatélites
6.
mSphere ; 3(3)2018.
Artigo em Inglês | MEDLINE | ID: mdl-29720528

RESUMO

USA500 isolates are clonal complex 8 (CC8) Staphylococcus aureus strains closely related to the prominent community- and hospital-associated USA300 group. Despite being relatively understudied, USA500 strains cause a significant burden of disease and are the third most common methicillin-resistant S. aureus (MRSA) strains identified in the U.S. Emerging Infections Program (EIP) invasive S. aureus surveillance. To better understand the genetic relationships of the strains, we sequenced the genomes of 539 USA500 MRSA isolates from sterile site infections collected through the EIP between 2005 and 2013 in the United States. USA500 isolates fell into three major clades principally separated by their distribution across different U.S. regions. Clade C1 strains, found principally in the Northeast, were associated with multiple IS256 insertion elements in their genomes and higher levels of antibiotic resistance. C2 was associated with Southern states, and E1 was associated with Western states. C1 and C2 strains all shared a frameshift in the gene encoding AdsA surface-attached surface protein. We propose that the term "USA500" should be used for CC8 strains sharing a recent common ancestor with the C1, C2, and E1 strains but not in the USA300 group.IMPORTANCE In this work, we have removed some of the confusion surrounding the use of the name "USA500," placed USA500 strains in the context of the CC8 group, and developed a strategy for assignment to subclades based on genome sequence. Our new phylogeny of USA300/USA500 will be a reference point for understanding the genetic adaptations that have allowed multiple highly virulent clonal strains to emerge from within CC8 over the past 50 years.


Assuntos
Staphylococcus aureus Resistente à Meticilina/classificação , Staphylococcus aureus Resistente à Meticilina/genética , Tipagem Molecular , Filogeografia , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Monitoramento Epidemiológico , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Epidemiologia Molecular , Estados Unidos/epidemiologia , Sequenciamento Completo do Genoma
7.
J Neurol Sci ; 252(1): 39-44, 2007 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-17113602

RESUMO

UNLABELLED: Lipoprotein (a) [Lp(a)] is a LDL-particle linked to apoprotein (a) [apo(a)]. High Lp(a) plasma level is a risk factor for coronary heart disease and, in older men, for ischemic stroke. The role of Lp(a) as a risk factor for ischemic stroke in young adults is uncertain. METHODS: Lp(a) concentration was prospectively measured in 100 consecutive patients with acute ischemic stroke (58 men and 42 women) aged 18-55 years, and in 100 controls matched for age and gender. RESULTS: The distribution of Lp(a) concentration was skewed toward the highest and median tertiles in male patients. In multivariate logistic regression analyses adjusting on classical risk factors for ischemic stroke and lipid variables, Lp(a) concentration in the highest and medium tertiles compared with the lowest tertile was significantly associated with ischemic stroke in men (OR 3.55, 95% CI 1.33-9.48, p = 0.012), but was not in women (OR 0.42, 95% CI 0.14-1.26, p = 0.12). Although large vessel atherosclerosis was more common in men than in women, there were no differences in Lp(a) concentration according to the cause of ischemic stroke. CONCLUSION: Among subjects aged 18-55 years, a slightly elevated Lp(a) concentration was strongly and independently associated with ischemic stroke in men, but not in women. Further studies are required to elucidate the mechanisms underlying this gender-specific association.


Assuntos
Isquemia Encefálica/metabolismo , Lipoproteínas/metabolismo , Risco , Acidente Vascular Cerebral/metabolismo , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Fatores Sexuais
9.
Leukemia ; 30(4): 897-905, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26500139

RESUMO

After failure of erythropoiesis-stimulating agents (ESAs), lenalidomide (LEN) yields red blood cell (RBC) transfusion independence (TI) in 20-30% of lower-risk non-del5q myelodysplastic syndrome (MDS). Several observations suggest an additive effect of ESA and LEN in this situation. We performed a randomized phase III study in 131 RBC transfusion-dependent (TD, median transfusion requirement six RBC units per 8 weeks) lower-risk ESA-refractory non-del5q MDS. Patients received LEN alone, 10 mg per day, 21 days per 4 weeks (L arm) or LEN (same schedule) + erythropoietin (EPO) beta, 60,000 U per week (LE arm). In an intent-to-treat (ITT) analysis, erythroid response (HI-E, IWG 2006 criteria) after four treatment cycles (primary end point) was 23.1% (95% CI 13.5-35.2) in the L arm and 39.4% (95% CI 27.6-52.2) in the LE arm (P=0.044), while RBC-TI was reached in 13.8 and 24.2% of the patients in the L and LE arms, respectively (P=0.13). Median response duration was 18.1 and 15.1 months in the L and LE arms, respectively (P=0.47). Side effects were moderate and similar in the two arms. Low baseline serum EPO level and a G polymorphism of CRBN gene predicted HI-E. Combining LEN and EPO significantly improves erythroid response over LEN alone in lower-risk non-del5q MDS patients with anemia resistant to ESA.


Assuntos
Transfusão de Sangue , Deleção Cromossômica , Cromossomos Humanos Par 5/genética , Eritropoetina/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Talidomida/análogos & derivados , Idoso , Anemia/prevenção & controle , Inibidores da Angiogênese/uso terapêutico , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Lenalidomida , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Fatores de Risco , Talidomida/uso terapêutico
10.
Genetics ; 144(3): 1237-45, 1996 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8913764

RESUMO

Estimates and variances of diversity and differentiation measures in subdivided populations are proposed that can be applied to haplotypes (ordered alleles such as DNA sequences, which may contain a record of their own histories). Hence, two measures of differentiation can be compared for a single data set: one (GST) that makes use only of the allelic frequencies and the other (NST) for which similarities between the haplotypes are taken into account in addition. Tests are proposed to compare NST and GST with zero and with each other. The difference between NST and GST can be caused by several factors, including sampling artefacts, unequal effect of mutation rates and phylogeographic structure. The method presented is applied to a published data set where a nuclear DNA sequence had been determined from individuals of a grasshopper distributed in 24 regions of Europe. Additional insights into the genetic subdivision of these populations are obtained by progressively combining related haplotypes and reanalyzing the data each time.


Assuntos
Alelos , Variação Genética , Computação Matemática , Modelos Genéticos , Animais , Gafanhotos/classificação , Gafanhotos/genética , Haplótipos
11.
Genetics ; 157(1): 389-97, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11139519

RESUMO

Variation at 12 polymorphic isozyme loci was studied in the European beech on the basis of an extensive sample of 389 populations distributed throughout the species range. Special emphasis was given to the analysis of the pattern of geographic variation on the basis of two contrasting measures of genetic diversity, gene diversity (H) and allelic richness, and to their relationship. Measures of allelic richness were corrected for variation in sample size by using the rarefaction method. As expected, maximum allelic richness was found in the southeastern part of the range (southern Italy and the Balkans), where beech was confined during the last ice age. Surprisingly, H was lower in refugia than in recently colonized regions, resulting in a negative correlation between the two diversity measures. The decrease of allelic richness and the simultaneous increase of H during postglacial recolonization was attributed to several processes that differentially affect the two diversity parameters, such as bottlenecks due to long-distance founding events, selection during population establishment, and increased gene flow at low population densities.


Assuntos
Árvores/genética , Alelos , Evolução Biológica , Europa (Continente) , Variação Genética , Genética Populacional , Heterozigoto , Isoenzimas/genética , Seleção Genética , Árvores/enzimologia
12.
Genetics ; 146(4): 1475-87, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9258689

RESUMO

Patterns of chloroplast DNA (cpDNA) variation were studied in eight white oak species by sampling 345 populations throughout Europe. The detection of polymorphisms by restriction analysis of PCR-amplified cpDNA fragments allowed the identification of 23 haplotypes that were phylogenetically ordered. A systematic hybridization and introgression between the eight species studied is evident. The levels of subdivision for unordered (GST) and ordered (NST) alleles are very high and close (0.83 and 0.85). A new statistical approach to the quantitative study of phylogeography is presented, which relies on the coefficients of differentiation GST and NST and the Mantel's test. Based on pairwise comparisons between populations, the significance of the difference between both coefficients is evaluated at a global and a local scale. The mapped distribution of the haplotypes indicates the probable routes of postglacial recolonization followed by oak populations that had persisted in southern refugia, especially in the Iberian peninsula, Italy and the Balkans. Most cpDNA polymorphisms appear to be anterior to the beginning of the last recolonization. A subset of the preexisting haplotypes have merely expanded north, while others were left behind in the south.


Assuntos
Árvores/genética , DNA de Cloroplastos/genética , Europa (Continente) , Evolução Molecular , Frequência do Gene , Variação Genética , Haplótipos , Filogenia , Polimorfismo de Fragmento de Restrição , Especificidade da Espécie
13.
Artigo em Francês | MEDLINE | ID: mdl-16327696

RESUMO

Thanks to better technique for cemented prostheses or to better osteointegration of porous coated implants, a long term survival can be expected for joint prostheses. Wear of the bearing surfaces resulting in osteolysis, metallosis and even rupture has become the main threat after several years. In such cases, revising all the parts of a stable and well fixed implant may cause fractures, loss of bone and thus need an extensive reconstruction. Revising only the worn out parts might be preferable, provided that they still are available. Data collected by the SFHG (French Hip and Knee Society) and AVIO group show that 45% of hip revisions and 16% of knee revisions are partial ones. The need for a total exchange instead of a partial one appeared in 6.4% of knee revisions and 2.8% of hip revisions, because parts were no longer available. These problems linked to a longer life expertancy of the patients and the increasing number of hip and knee arthroplasties will be met more and more often by orthopedic surgeons. When parts identical to the worn out ones are still on the market, there is no problem. When their production has been given up, but the company has kept their references and accepts to make a single element it may be possible to obtain the missing unit. The increased cost of such a fabrication, however is not nowadays supported by an appropriate price. But in a few remaining cases without enough industrial references, a custom-made part had to be done to allow partial replacement, with the benefit of an adapted price. Care must be taken to observe the regulations. The surgeon endorses full responsibility not only for the surgical procedure but also for the choice of the implanted device. For custom-made products he is responsible for the technical data given to the company. The patient must be thoroughly informed, and his opinion taken into account in the operative decision. As a revision arthroplasty aims at restoring a good function, the procedure should suit best the patient's health condition and try and avoid any hazard. Rejecting the option of partial replacement just because of parts unavailability is not acceptable when it seems the safest way to get the best result. Help can come from orthopedic surgeons themselves, if they give to their patient precise reports on the primary arthroplasty. The technical references of all the devices devoted to joint arthroplasty should not only be collected by public health services (AFSSAPS) but they should also be available to orthopedic surgeons. The real production cost of prosthetic elements should be taken into account in order to encourage the companies to deliver parts that are not on the market anymore.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Falha de Prótese , Tomada de Decisões , Humanos , Consentimento Livre e Esclarecido , Desenho de Prótese , Reoperação , Fatores de Tempo
14.
Evolution ; 55(6): 1123-35, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11475048

RESUMO

We examined the spatial distribution of maternally inherited chloroplast DNA markers over the French part of the range of Sorbus torminalis, a scattered temperate forest tree native to most of Europe. The survey by restriction analysis of polymerase-chain-reaction amplified fragments for 880 individuals distributed among 55 populations allowed the detection of 25 haplotypes. The coefficient of differentiation among populations computed on the basis of haplotype frequency (G(STc) = 0.34) was one of the lowest found in forest trees so far, and the mean within-population diversity was relatively high, indicating multiple-mother foundation events. A significant but slight geographical pattern was observed, up to distances of about 100 km. This pattern of differentiation was compared to the genetic structure of the same populations revealed by biparentally inherited markers (isoenzymes), and a new method to quantify the relative importance of seed and pollen dispersal was derived, based on isolation-by-distance models. Neither pollen- nor seed-mediated gene flow was predominant in S. torminalis, a finding that differs from those for the majority of tree species studied so far. This result was most likely due to an extinction-recolonization dynamics based on efficient seed dispersal strategies. The joint screening of 31 individuals of the related Sorbus aria and of 163 hybrid individuals shows that hybridization occurs predominantly in one direction and is rarely followed by cytoplasmic introgression. As a consequence, interspecific gene flow should not significantly affect the diversity dynamics within S. torminalis.


Assuntos
Variação Genética , Filogenia , Pólen/fisiologia , Rosales/genética , Sementes/fisiologia , Árvores/genética , Cloroplastos/genética , DNA Complementar/genética , DNA de Plantas/genética , França , Marcadores Genéticos , Haplótipos/genética , Isoenzimas/genética , Rosales/classificação , Especificidade da Espécie , Árvores/classificação
15.
J Endocrinol ; 111(2): 301-8, 1986 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-3098889

RESUMO

Changes in the concentrations of LH and FSH testicular receptors have been studied in the pig, from neonatal to adult life, and correlated with blood LH, FSH and testosterone concentrations. Quantification of gonadotrophin receptors was performed in equilibrium binding studies, using homologous systems. The presence of high-affinity binding sites for LH and FSH (association constant (Ka): LH approximately 20 litres/nmol; FSH approximately 10 litres/nmol) was demonstrated in the testes of all animals studied. The apparent affinity of LH and FSH receptors did not change significantly with age. During the first weeks of life, there was a transient rise in LH receptor content, reaching a maximum of 8.7 +/- 2.2 (mean +/- S.E.M.) pmol/g testis at 24 days of age. This was correlated with a peak in testosterone secretion and reflects the second wave of interstitial cell proliferation in the pig. A second increase in the number of LH receptors occurred after 12 weeks of age and corresponds to pubertal maturation and final differentiation of adult Leydig cells. During this period, circulating concentrations of testosterone markedly increased without any significant variation in LH blood levels, suggesting a change in testicular sensitivity to LH in the maturing pig. A continuous increase in FSH receptor content was observed from the neonatal to the adult pig. This increase occurred in two phases. During the first 2 months of life, the increase in the number of FSH receptors exceeded that of testis growth rate and resulted in an increase in FSH receptor concentrations which reached a peak at 12.1 +/- 1.8 pmol/g testis, at week 9.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Receptores da Gonadotropina/metabolismo , Maturidade Sexual , Suínos/metabolismo , Testículo/metabolismo , Animais , Animais Recém-Nascidos , Masculino , Receptores do FSH/metabolismo , Receptores do LH/metabolismo , Testículo/crescimento & desenvolvimento , Testosterona/sangue
16.
J Appl Physiol (1985) ; 79(1): 229-35, 1995 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7559224

RESUMO

We previously found that augmentation of polycythemia by exogenous human recombinant erythropoietin (EPO) failed to worsen the severity of hypoxic pulmonary hypertension in rats. We asked whether this unexpected finding was related to reductions in cardiac output, left ventricular end-diastolic pressure, pulmonary vascular resistance, or some combination of these factors. Four groups of Sprague-Dawley rats were studied over a 3-wk period: hypoxic (0.5 ATM) and normoxic animals each injected with EPO (500 U/kg sc thrice weekly) or saline (control animals). As observed previously, we found that pulmonary arterial (PA) pressures and right ventricular hypertrophy were not increased in EPO-treated rats despite significant increases in hematocrit and blood viscosity. Cardiac outputs, blood volumes, and left ventricular end-diastolic pressures were similar in EPO-treated and control rats. Acute PA pressure responses to acute normoxia in hypoxic rats and to acute hypoxia in normoxic rats were similar, suggesting no differences in vasoreactivity. However, lungs isolated from EPO-treated hypoxic rats had lower pulmonary vascular resistance than saline-treated hypoxic rats when perfused with blood from normocythemic donor rats. PA medial thickness and the percentage of muscularized small PAs were significantly lower in EPO-treated hypoxic rats. These results indicate that augmented polycythemia fails to worsen hypoxic pulmonary hypertension in rats because of a decrease in the severity of structural remodeling.


Assuntos
Adaptação Fisiológica , Hipóxia/fisiopatologia , Policitemia/fisiopatologia , Circulação Pulmonar , Animais , Pressão Sanguínea/efeitos dos fármacos , Vasos Sanguíneos/patologia , Viscosidade Sanguínea , Doença Crônica , Eritropoetina/sangue , Eritropoetina/farmacologia , Hematócrito , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Circulação Pulmonar/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes
17.
J Appl Physiol (1985) ; 75(4): 1615-23, 1993 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8282611

RESUMO

Neutral endopeptidase (NEP) inhibition is thought to blunt hypoxic pulmonary hypertension by reducing atrial natriuretic peptide (ANP) metabolism, but this hypothesis has not been confirmed. We measured NEP activity, guanosine 3',5'-cyclic monophosphate (cGMP) production, plasma ANP levels, and cardiac ANP synthesis in rats given an orally active NEP inhibitor (SCH-34826) during 3 wk of hypoxia. Under normoxic conditions, SCH-34826 had no effect on plasma ANP levels but reduced pulmonary and renal NEP activity by 50% and increased urinary cGMP levels (60 +/- 6 vs. 22 +/- 4 pg/mg creatinine; P < 0.05). Under hypoxic conditions, SCH-34826-treated rats had lower plasma ANP levels (1,259 +/- 361 vs. 2,101 +/- 278 pg/ml; P < 0.05), lower right ventricular systolic pressure (53 +/- 5 vs. 73 +/- 2 mmHg; P < 0.05), lower right ventricle weight-to-left ventricle+septum weight ratio (0.47 +/- 0.04 vs. 0.53 +/- 0.03; P < 0.05), and less muscularization and percent medial wall thickness of peripheral pulmonary arteries (22 +/- 5 vs. 45 +/- 8% and 17 +/- 1 vs. 25 +/- 1%, respectively; P < 0.05 for all values) than did rats treated with vehicle alone. These values were not affected by SCH-34826 under normoxic conditions. SCH-34826 decreased right ventricular ANP tissue levels in hypoxic rats (27 +/- 10 vs. 8 +/- 1 ng/mg protein; P < 0.05) but did not affect steady-state ANP mRNA levels. We conclude that NEP inhibition blunts pulmonary hypertension without increasing plasma ANP levels.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Hipertensão Pulmonar/prevenção & controle , Hipóxia/fisiopatologia , Neprilisina/antagonistas & inibidores , Animais , Fator Natriurético Atrial/biossíntese , Pressão Sanguínea/efeitos dos fármacos , Doença Crônica , GMP Cíclico/urina , Dioxolanos/farmacologia , Dipeptídeos/farmacologia , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/metabolismo , Hipertrofia Ventricular Direita/etiologia , Hipertrofia Ventricular Direita/fisiopatologia , Hipóxia/complicações , Hipóxia/metabolismo , Imidazóis/farmacologia , Masculino , Músculo Liso Vascular/fisiopatologia , Miocárdio/metabolismo , Pirazinas/farmacologia , RNA Mensageiro/biossíntese , Ratos , Ratos Sprague-Dawley
18.
J Appl Physiol (1985) ; 75(1): 198-205, 1993 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7690745

RESUMO

Elevated plasma atrial natriuretic peptide (ANP) levels have been shown to blunt pulmonary hemodynamic responses to chronic hypoxia, but whether elevated circulating ANP levels negatively feedback on cardiac expression of the ANP gene is unknown. Using a recently developed strain of transgenic mouse (TTR-ANF) that expresses a transthyretin promoter-ANP fusion gene in the liver, we studied the effect of chronically elevated plasma ANP levels on cardiac hypertrophic and pulmonary hemodynamic responses and expression of the endogenous cardiac ANP gene during chronic hypoxia. Plasma ANP levels were 10-fold higher in TTR-ANF mice than in their non-transgenic littermates. After 3 wk of hypobaric hypoxia (0.5 atm), right ventricular hypertrophy and pulmonary hypertension had developed in both groups of mice, but TTR-ANF mice had lower right ventricle-to-left ventricle plus septum weight ratios (0.39 +/- 0.01 vs. 0.45 +/- 0.02), right ventricular systolic pressures (25 +/- 2 vs. 29 +/- 2 mmHg), and lung dry weight-to-body weight ratios (0.48 +/- 0.03 vs. 0.57 +/- 0.01 mg/g) and less muscularization of peripheral pulmonary vessels (8.3 +/- 1.4 vs. 17.4 +/- 2.5%) than nontransgenic controls. Right atrial and ventricular steady-state ANP mRNA levels were the same in both groups of mice under normoxic and hypoxic conditions despite much higher plasma ANP levels and less pulmonary hypertension in TTR-ANF mice. We conclude that chronically elevated plasma ANP levels attenuate the development of hypoxic pulmonary hypertension in mice but do not suppress cardiac expression of the endogenous ANP gene under normoxic conditions nor blunt the upregulation of right ventricular ANP expression during chronic hypoxia.


Assuntos
Fator Natriurético Atrial/biossíntese , Coração/fisiopatologia , Hipóxia/fisiopatologia , Pulmão/fisiopatologia , Animais , Fator Natriurético Atrial/sangue , Fator Natriurético Atrial/genética , Pressão Sanguínea/fisiologia , Northern Blotting , Peso Corporal/fisiologia , Retroalimentação/fisiologia , Feminino , Coração/anatomia & histologia , Hematócrito , Hemodinâmica/fisiologia , Hipertensão Pulmonar/fisiopatologia , Hipertrofia Ventricular Direita/fisiopatologia , Pulmão/anatomia & histologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Circulação Pulmonar/fisiologia , RNA/isolamento & purificação , Regulação para Cima/fisiologia
19.
Oncology (Williston Park) ; 12(8 Suppl 6): 68-71, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9726095

RESUMO

Most of the clinical experience with irinotecan (CPT-11 [Camptosar]) has been with either a weekly or an every-3-week schedule. Recent phase I trials have explored new routes and schedules of administration. One approach attempts to maximize dose frequency and intensity by giving irinotecan every 2 weeks. A phase I trial of this approach is now complete and has led to a phase II trial in patients with recurrent colorectal cancer. Data suggest that smaller doses of a topoisomerase I inhibitor administered repeatedly may result in greater antitumor activity than large doses administered intermittently. A phase I trial has been performed in adults in which irinotecan was administered daily for 5 consecutive days, followed by 2 days off, for 2 weeks out of 3. Similar trials are under way in children. Oral administration, another strategy that has undergone phase I testing, has several theoretical advantages:(1) The acidic pH of the stomach favors maintenance of irinotecan in the active lactone ring form. (2) Irinotecan is more rapidly and extensively converted to SN-38 by tissue carboxylesterases found in high concentrations in the gut and liver. (3) Low doses can be delivered over a protracted period. (4) The oral route enhances patient convenience. These alternative dosing schedules may facilitate integration of irinotecan into combination chemotherapy and combined-modality treatment regimens.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Camptotecina/análogos & derivados , Adulto , Camptotecina/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Humanos , Irinotecano
20.
Heart Lung ; 26(3): 221-8, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9176690

RESUMO

OBJECTIVES: To describe how nurses assess and manage pain in critically ill children. DESIGN: Descriptive, comparative research design, with use of the Indicators of Pain in Critically Ill Children assessment tool. SETTING: Twelve-bed pediatric intensive care unit in a metropolitan general hospital with a level II pediatric trauma center. PARTICIPANTS: Twenty-four pediatric intensive care unit nurses who conducted 112 assessments of 25 critically ill children. RESULTS: Pain indicators selected most frequently by nurses included cardiovascular and respiratory changes (increased heart rate, respiratory rate, and blood pressure), followed by behavioral indicators (irritable/fussy, verbalizing pain, crying), and neuromuscular responses (tenseness/rigidity, squirming, drawing up legs). The average number of pain indicators selected during each medication event was 5.3. More indicators were selected for trauma, surgery, and younger patients; fewer indicators were selected for patients receiving ventilation treatment. CONCLUSION: Pain assessment of critically ill children includes unique indicators, as compared to less sick children, and must take into account the child's decreased ability to communicate pain.


Assuntos
Cuidados Críticos , Avaliação em Enfermagem , Medição da Dor/enfermagem , Dor/enfermagem , Adolescente , Analgésicos Opioides/administração & dosagem , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Variações Dependentes do Observador , Dor/classificação
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