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The evaluation of electrostatic energy for a set of point charges in a periodic lattice is a computationally expensive part of molecular dynamics simulations (and other applications) because of the long-range nature of the Coulomb interaction. A standard approach is to decompose the Coulomb potential into a near part, typically evaluated by direct summation up to a cutoff radius, and a far part, typically evaluated in Fourier space. In practice, all decomposition approaches involve approximations-such as cutting off the near-part direct sum-but it may be possible to find new decompositions with improved trade-offs between accuracy and performance. Here, we present the u-series, a new decomposition of the Coulomb potential that is more accurate than the standard (Ewald) decomposition for a given amount of computational effort and achieves the same accuracy as the Ewald decomposition with approximately half the computational effort. These improvements, which we demonstrate numerically using a lipid membrane system, arise because the u-series is smooth on the entire real axis and exact up to the cutoff radius. Additional performance improvements over the Ewald decomposition may be possible in certain situations because the far part of the u-series is a sum of Gaussians and can thus be evaluated using algorithms that require a separable convolution kernel; we describe one such algorithm that reduces communication latency at the expense of communication bandwidth and computation, a trade-off that may be advantageous on modern massively parallel supercomputers.
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Organic agricultural systems are often assumed to be more sustainable than conventional farming, yet there has been little work comparing surface water quality from organic and conventional production, especially under the same cropping sequence. Our objective was to compare nutrient and sediment losses, as well as sweet corn ( L. var. ) yield, from organic and conventional production with conventional and conservation tillage. The experiment was located in the Appalachian Mountains of North Carolina. Four treatments, replicated four times, had been in place for over 18 yr and consisted of conventional tillage (chisel plow and disk) with conventional production (CT/Conven), conservation no-till with conventional production (NT/Conven), conventional tillage with organic production (CT/Org), and conservation no-till with organic production (NT/Org). Water quality (surface flow volume; nitrogen, phosphorus, and sediment concentrations) and sweet corn yield data were collected in 2011 and 2012. Sediment and sediment-attached nutrient losses were influenced by tillage and cropping system in 2011, due to higher rainfall, and tillage in 2012. Soluble nutrients were affected by the nutrient source and rate, which are a function of the cropping system. Sweet corn marketable yields were greater in conventional systems due to high weed competition and reduced total nitrogen availability in organic treatments. When comparing treatment efficiency (yield kg ha /nutrient loss kg ha ), the NT/Conven treatment had the greatest sweet corn yield per unit of nutrient and sediment loss. Other treatment ratios were similar to each other; thus, it appears the most sustainably productive treatment was NT/Conven.
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Autosomal dominant gain of function mutations in the gene encoding PI3K p110δ were recently associated with a novel combined immune deficiency characterized by recurrent sinopulmonary infections, CD4 lymphopenia, reduced class-switched memory B cells, lymphadenopathy, CMV and/or EBV viremia and EBV-related lymphoma. A subset of affected patients also had elevated serum IgM. Here we describe three patients in two families who were diagnosed with HIGM at a young age and were recently found to carry heterozygous mutations in PIK3CD. These patients had an abnormal circulating B cell distribution featuring a preponderance of early transitional (T1) B cells and plasmablasts. When stimulated in vitro, PIK3CD mutated B cells were able to secrete class-switched immunoglobulins. This finding implies that the patients' elevated serum IgM levels were unlikely a product of an intrinsic B cell functional inability to class switch. All three patients developed malignant lymphoproliferative syndromes that were not associated with EBV. Thus, we identified a novel subset of patients with PIK3CD mutations associated with HIGM, despite indications of preserved in vitro B cell class switch recombination, as well as susceptibility to non-EBV-associated malignancies.
Assuntos
Classe I de Fosfatidilinositol 3-Quinases/genética , Predisposição Genética para Doença , Síndrome de Imunodeficiência com Hiper-IgM/complicações , Síndrome de Imunodeficiência com Hiper-IgM/genética , Mutação , Neoplasias/etiologia , Adulto , Biópsia , Criança , Feminino , Heterozigoto , Humanos , Síndrome de Imunodeficiência com Hiper-IgM/diagnóstico , Linfonodos/patologia , Masculino , Neoplasias/diagnóstico , Linhagem , Adulto JovemRESUMO
The Lupus Foundation of America (LFA) convened an international working group to obtain a consensus definition of disease flare in lupus. With help from the Paediatric Rheumatology International Trials Organization (PRINTO), two web-based Delphi surveys of physicians were conducted. Subsequently, the LFA held a second consensus conference followed by a third Delphi survey to reach a community-wide agreement for flare definition. Sixty-nine of the 120 (57.5%) polled physicians responded to the first survey. Fifty-nine of the responses were available to draft 12 preliminary statements, which were circulated in the second survey. Eighty-seven of 118 (74%) physicians completed the second survey, with an agreement of 70% for 9/12 (75%) statements. During the second conference, three alternative flare definitions were consolidated and sent back to the international community. One hundred and sixteen of 146 (79.5%) responded, with agreement by 71/116 (61%) for the following definition: "A flare is a measurable increase in disease activity in one or more organ systems involving new or worse clinical signs and symptoms and/or laboratory measurements. It must be considered clinically significant by the assessor and usually there would be at least consideration of a change or an increase in treatment." The LFA proposes this definition for lupus flare on the basis of its high face validity.
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Lúpus Eritematoso Sistêmico/diagnóstico , Terminologia como Assunto , Doença Aguda , Técnica Delphi , Humanos , InternacionalidadeRESUMO
Polycyclic heavy hydrocarbons (HHs) such as coal, tar, and pitch are a family of materials with extremely rich and complex chemistry, representing a massive opportunity for their use in a range of potential applications. The present work shows that optimal selection of initial HHs based on molecular constituents is essential in tuning the material for a particular and targeted electronic application. Combining the selection of feedstock chemistry (H:C and aromatic content) and controlling variable laser treatment parameters (laser power, speed, and focus) lead to full control over the H:C ratio, sp2 concentration, and degree of graphitic stacking order of the products. The broad intertunability of these factors results from a wide distribution of carbon material crystallinity from amorphous to highly graphitic and a broad distribution of electrical conductivity up to 103 S/m.
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Primitive meteorites provide a glimpse into the early history of our solar system, but some of the most primitive meteorites are also rarely found on Earth. In his Perspective, Grossman explains why the fall of the Tagish Lake meteorite on 18 January 2000 in British Columbia, Canada, was a lucky event for meteorite researchers. The first analysis of the meteorite is reported by Brown et al. Well-preserved organic matter in the meteorite provides a unique opportunity to study the nature and origin of organic matter that may have accreted on early Earth and played a role in the origin of life.
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Fine-grained samples disrupted after exposure to oxygen and oxygen with 3.5 percent water above 2 torr. Chemical etching revealed plastic deformation in some samples, adhesion due to impact melting in others, dislocations in crystalline phases and evidence that some glasses were partially devitrified. Specimens of rock that were fractured in ultrahigh vacuum exhibited a time-dependent adhesion and a network of localized electrostatically charged areas.
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Rhenium and osmium concentrations and the osmium isotopic compositions of iron meteorites were determined by negative thermal ionization mass spectrometry. Data for the IIA iron meteorites define an isochron with an uncertainty of approximately +/-31 million years for meteorites approximately 4500 million years old. Although an absolute rheniumosmium closure age for this iron group cannot be as precisely constrained because of uncertainty in the decay constant of (187)Re, an age of 4460 million years ago is the minimum permitted by combined uncertainties. These age constraints imply that the parent body of the IIAB magmatic irons melted and subsequently cooled within 100 million years after the formation of the oldest portions of chondrites. Other iron meteorites plot above the IIA isocbron, indicating that the planetary bodies represented by these iron groups may have cooled significantly later than the parent body of the IIA irons.
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Microbial community composition was examined in two soil types, Anthrosols and adjacent soils, sampled from three locations in the Brazilian Amazon. The Anthrosols, also known as Amazonian dark earths, are highly fertile soils that are a legacy of pre-Columbian settlement. Both Anthrosols and adjacent soils are derived from the same parent material and subject to the same environmental conditions, including rainfall and temperature; however, the Anthrosols contain high levels of charcoal-like black carbon from which they derive their dark color. The Anthrosols typically have higher cation exchange capacity, higher pH, and higher phosphorus and calcium contents. We used culture media prepared from soil extracts to isolate bacteria unique to the two soil types and then sequenced their 16S rRNA genes to determine their phylogenetic placement. Higher numbers of culturable bacteria, by over two orders of magnitude at the deepest sampling depths, were counted in the Anthrosols. Sequences of bacteria isolated on soil extract media yielded five possible new bacterial families. Also, a higher number of families in the bacteria were represented by isolates from the deeper soil depths in the Anthrosols. Higher bacterial populations and a greater diversity of isolates were found in all of the Anthrosols, to a depth of up to 1 m, compared to adjacent soils located within 50-500 m of their associated Anthrosols. Compared to standard culture media, soil extract media revealed diverse soil microbial populations adapted to the unique biochemistry and physiological ecology of these Anthrosols.
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Bactérias/genética , Bactérias/isolamento & purificação , Microbiologia do Solo , Bactérias/classificação , Brasil , Meios de Cultura , DNA Bacteriano/genética , Filogenia , Polimorfismo de Fragmento de Restrição , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Solo/análise , Clima TropicalRESUMO
Tailoring the structural and electronic properties of 2D materials is fundamental to boost their use in a wide range of technological applications. In this paper, by means of first principles simulations, we show how methyl functionalization of MoS2 and WS2 monolayers can be employed to change their energy gap, tune their optoelectronic properties and modify the relative stability of their structural phases (or polytypes). In particular for both compound monolayers, we find that the most stable semiconducting H phase becomes metallic upon methyl functionalization, while in the metastable T' phase the band gap increases as a function of the -CH3 coverage; correspondingly the phase stability is reversed and the on-set of the optical absorption is blue-shifted.
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Previous work has suggested that intracellular proteolysis may play a role in lymphocyte stimulation. An inhibitor of proteolysis, epsilon amino caproic acid (EACA) was studied for its effect on the lymphocyte response to phytohemagglutinin (PHA). EACA was found to inhibit several parameters of lymphocyte stimulation (e.g. DNA, RNA, and protein synthesis as well as alterations in morphology) This inhibition was not due to diminished cellular viability and did not permanently impair the capacity of the lymphocyte to subsequently respond to PHA. Additionally, there was no evidence that this inhibition was due to other possible effects of EACA, such as alterations in Na(+) - K(+) transport, competitive amino acid deprivation or interference with PHA binding. Moreover, the inhibitors of proteolysis, tosyl arginine methyl ester (TAME), tosyl lysine chloromethyl ketone (TLCK), and tosyl phenyl-alanine chloromethyl ketone (TPCK), were also shown to inhibit lymphocyte stimulation.EACA was most effective when added during the first 24 hr of stimulation. Therefore, these experiments support the hypothesis that proteolysis is an essential step in the early phase of lymphocyte activation.
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Aminocaproatos/farmacologia , Proteínas Sanguíneas/biossíntese , DNA/biossíntese , Antagonismo de Drogas , Lectinas/antagonistas & inibidores , Linfócitos/imunologia , RNA/biossíntese , Arginina , Isótopos de Carbono , Técnicas de Cultura , Depressão Química , Ésteres/farmacologia , Humanos , Cetonas/farmacologia , Leucina/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Lisina , Fenilalanina , Estimulação Química , Timidina/metabolismo , Uridina/metabolismoRESUMO
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by various autoantibodies that recognize autoantigens displayed on the surface of cells undergoing apoptosis. The genetic contribution to SLE susceptibility has been widely recognized. We previously reported evidence for linkage to SLE of the human chromosome 1q41-q42 region and have now narrowed it from 15 to 5 cM in an extended sample using multipoint linkage analysis. Candidate genes within this region include (a) PARP, poly(ADP-ribose) polymerase, encoding a zinc-finger DNA-binding protein that is involved in DNA repair and apoptosis; (b) TGFB2, encoding a transforming growth factor that regulates cellular interactions and responses; and (c) HLX1, encoding a homeobox protein that may regulate T-cell development. Using a multiallelic, transmission-disequilibrium test (TDT), we found overall skewing of transmission of PARP alleles to affected offspring in 124 families (P = 0.00008), preferential transmission of a PARP allele to affected offspring (P = 0.0003), and lack of transmission to unaffected offspring (P = 0.004). Similar TDT analyses of TGFB2 and HLX1 polymorphisms yielded no evidence for association with SLE. These results suggest that PARP may be (or is close to) the susceptibility gene within the chromosome 1q41-q42 region linked to SLE.
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Alelos , Ligação Genética , Lúpus Eritematoso Sistêmico/enzimologia , Lúpus Eritematoso Sistêmico/genética , Poli(ADP-Ribose) Polimerases/genética , Mapeamento Cromossômico , Humanos , Desequilíbrio de Ligação , Fator de Crescimento Transformador beta/genéticaRESUMO
Growth factors and cyclic AMP (cAMP) are known to activate distinct intracellular signaling pathways. Fibroblast growth factor (FGF) activates ras-dependent kinase cascades, resulting in the activation of MAP kinases, whereas cAMP activates protein kinase A. In this study, we report that growth factors and cAMP act synergistically to stimulate proenkephalin gene expression. Positive synergy between growth factor- and cAMP-activated signaling pathways on gene expression has not been previously reported, and we suggest that these synergistic interactions represent a useful model for analyzing interactions between these pathways. Transfection and mutational studies indicate that both FGF-dependent gene activation and cAMP-dependent gene activation require cAMP response element 2 (CRE-2), a previously characterized cAMP-dependent regulatory element. Furthermore, multiple copies of this element are sufficient to confer FGF regulation upon a minimal promoter, indicating that FGF and cAMP signaling converge upon transcription factors acting at CRE-2. Among many different ATF/AP-1 factors tested, two factors, ATF-3 and c-Jun, stimulate proenkephalin transcription in an FGF- or Ras-dependent fashion. Finally, we show that ATF-3 and c-Jun form heterodimeric complexes in SK-N-MC cells and that the levels of both proteins are increased in response to FGF but not cAMP. Together, these results indicate that growth factor- and cAMP-dependent signaling pathways converge at CRE-2 to synergistically stimulate gene expression and that ATF-3 and c-Jun regulate proenkephalin transcription in response to both growth factor- and cAMP-dependent intracellular signaling pathways.
Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , AMP Cíclico/farmacologia , Fatores de Crescimento de Fibroblastos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Fator 2 Ativador da Transcrição , Fator 3 Ativador da Transcrição , Sequência de Bases , Linhagem Celular , AMP Cíclico/administração & dosagem , AMP Cíclico/metabolismo , Primers do DNA/genética , Sinergismo Farmacológico , Encefalinas/genética , Fatores de Crescimento de Fibroblastos/administração & dosagem , Genes ras , Humanos , Dados de Sequência Molecular , Precursores de Proteínas/genética , Proteínas Proto-Oncogênicas c-jun/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Ativação Transcricional , TransfecçãoRESUMO
Epidemiological studies suggest that moderate alcohol consumption increases the risk of breast cancer, and that alcohol combined with estrogen replacement therapy may synergistically enhance the risk. However, the mechanism(s) of alcohol-induced mammary cancer is unknown. In human breast cancer cell lines, we found that ethanol (EtOH) caused a dose-dependent increase of up to 10- to 15-fold in the transcriptional activity of the liganded estrogen receptor (ER-alpha), but did not activate the nonliganded receptor. Significant stimulation of ER-alpha activity was observed at EtOH concentrations comparable with or less than blood alcohol levels associated with intoxication and at doses below the threshold for in vitro cytotoxicity. These findings may be explained, in part, by an EtOH-induced down-regulation of the expression of BRCA1, a potent inhibitor of ER-alpha activity, and, in part, by a modest increase in the ER-alpha levels. Our findings suggest that inactivation of BRCA1 and increased estrogen-responsiveness might contribute to alcohol-induced breast cancer.
Assuntos
Neoplasias da Mama/metabolismo , Etanol/efeitos adversos , Receptores de Estrogênio/fisiologia , Transdução de Sinais/efeitos dos fármacos , Proteína BRCA1/biossíntese , Proteína BRCA1/genética , Proteína BRCA1/fisiologia , Neoplasias da Mama/etiologia , Neoplasias da Mama/genética , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Receptor alfa de Estrogênio , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genes BRCA1/efeitos dos fármacos , Genes BRCA1/genética , Humanos , Neoplasias Hormônio-Dependentes/etiologia , Neoplasias Hormônio-Dependentes/genética , Neoplasias Hormônio-Dependentes/metabolismo , Receptores de Estrogênio/antagonistas & inibidores , Receptores de Estrogênio/efeitos dos fármacos , Transdução de Sinais/fisiologia , Ativação Transcricional/efeitos dos fármacos , Ativação Transcricional/fisiologia , Células Tumorais CultivadasRESUMO
After review of the published clinical experience with systemic hypothermia, we concluded that a simple system which controls radiant heat balance to supplement metabolic heat might provide several advantages, including: (a) decreased morbidity; (b) elimination of the requirement for general anesthesia; (c) improved patient comfort; (d) favorable cost-benefit considerations. We have tested a prototype radiant heat device for whole-body hyperthermia (WBH) in patients with disseminated cancer. From preclinical evaluation of this device, the lightly anesthetized pig was found to be an ideal model for WBH. This species has physiological characteristics closely resembling those of humans. The pig's core, pulmonary artery, liver, rectal, and esophageal temperatures were raised to 41.8 degrees in 80 to 90 min. The air temperatures near the chamber wall never exceeded 65 degrees while the air temperature adjacent to the animal was 46 degrees. Skin temperatures were approximately 42.5 degrees at a core temperature of 41.8 degrees. Once the core temperature is raised to 41.8 degrees, this temperature is maintainable for approximately 3.5 hr without additional external heating if evaporative losses are controlled. Prolonged WBH was accomplished with light sedation and without the requirement for endotracheal intubation. No significant acute toxicity was encountered in a series of 6 pigs undergoing 9 separate exposures to WBH. From these results, we conclude that our radiant heat apparatus is feasible for clinical trials. Additionally, the use of the pig as an appropriate animal model for further physiological and pharmacological WBH studies is strongly recommended.
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Temperatura Corporal , Equipamentos e Provisões , Temperatura Alta/uso terapêutico , Neoplasias/terapia , Animais , Pressão Sanguínea , Débito Cardíaco , Estudos de Avaliação como Assunto , Feminino , Umidade , Suínos , Fatores de TempoRESUMO
A Phase I study of whole-body hyperthermia (WBH) (52 treatments/12 patients) was completed with no significant clinical toxicity. The study incorporated a thermal dose escalation scheme from 39.5 degrees-41.8 degrees C for up to 151 min. A radiant-heat device was utilized for producing WBH. During WBH, patients were sedated; endotracheal intubation was not required. No changes in cardiovascular, respiratory, hematological, or biochemical indices requiring clinical intervention occurred during the study. We conclude the radiant-heat device coupled with a defined pharmacological approach to WBH with appropriate patient screening yields a system for 41.8 degrees C WBH which is safe and efficient, is not labor intensive, and does not require general anesthesia and endotracheal intubation. This system is appropriate for a multimodality approach to various systemic cancers.
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Hipertermia Induzida/instrumentação , Neoplasias/terapia , Adolescente , Adulto , Fosfatase Alcalina/análise , Aspartato Aminotransferases/sangue , Contagem de Células Sanguíneas , Glicemia/análise , Creatina Quinase/sangue , Estudos de Avaliação como Assunto , Feminino , Coração/fisiopatologia , Humanos , Hipertermia Induzida/efeitos adversos , L-Lactato Desidrogenase/sangue , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/fisiopatologiaRESUMO
OBJECTIVES: We sought to investigate the cardiac effects of growth hormone (GH) administration during the early phase of pathologic remodeling in a rat model of large myocardial infarction (MI). BACKGROUND: Recent evidence suggests that exogenous administration of GH evokes a hypertrophic response and increases left ventricular (LV) function in vivo in rats with normal or chronically failing hearts. We hypothesized that these effects would attenuate ventricular remodeling early after MI. METHODS: Fifty-eight male rats underwent sham operation (n = 19) or had induced MI (n = 39). The day after the operation, the infarcted rats were randomized to receive 3 weeks of treatment with GH, 3 mg/kg body weight per day (n = 19) or placebo (n = 20). Echocardiography, catheterization and isolated whole heart preparations were used to define cardiac structure and function. RESULTS: Growth hormone caused hypertrophy of the noninfarcted myocardium in a concentric pattern, as noted by higher echocardiographic relative wall thickness at 3 weeks and by morphometric histologic examination. Left ventricular dilation was reduced in the GH-treated versus placebo group (echocardiographic LV diastolic diameter to body weight ratio 2.9 +/- 0.1 vs. 3.5 +/- 0.2 cm/kg; p < 0.05). In vivo and in vitro cardiac function was improved after GH treatment. Despite elevated insulin-like growth factor-1 (IGF-1) serum levels in GH-treated rats, myocardial IGF-I messenger ribonucleic acid was not different among the three groups, suggesting that an increase in its local expression does not appear necessary to yield the observed effects. CONCLUSIONS: These data demonstrate that early treatment of large MI with GH attenuates the early pathologic LV remodeling and improves LV function.
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Hormônio do Crescimento/farmacologia , Ventrículos do Coração/patologia , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Função Ventricular Esquerda/efeitos dos fármacos , Animais , Ecocardiografia , Hormônio do Crescimento/uso terapêutico , Ventrículos do Coração/efeitos dos fármacos , Hipertrofia , Immunoblotting , Técnicas In Vitro , Fator de Crescimento Insulin-Like I/análise , Masculino , Infarto do Miocárdio/diagnóstico por imagem , Miocárdio/patologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
An essential feature of the mechanism of nitrogenase, the enzyme responsible for biological nitrogen fixation, is the formation of a transient electron transfer complex between the MoFe protein containing the active site at which N2 is reduced, and the Fe protein, which functions as a specific electron donor to the MoFe protein. We have obtained high quality solution X-ray scattering data using synchrotron X-rays of a stable putative electron transfer complex, (MoFe-protein)(Fe-protein.ADP.AIF4)2, of Klebsiella pneumoniae and used the model-independent approach based on the multipole expansion method to provide a stable and unique shape restoration at approximately 15 A resolution. The biological significance of this first molecular structure of a nitrogenase complex is discussed.
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Klebsiella pneumoniae/enzimologia , Molibdoferredoxina/química , Nitrogenase/química , Azotobacter vinelandii/química , Transporte de Elétrons , Modelos Moleculares , Nitrogênio/metabolismo , Conformação Proteica , Espalhamento de Radiação , Raios XRESUMO
Treatment with GH attenuates remodeling and improves left ventricular function in the setting of experimental heart failure following coronary ligation. This study was designed to test the hypothesis that an intact GH/insulin-like growth factor 1 (IGF-1) axis is required for normal myocardial infarction healing. Myocardial infarction was induced by coronary ligation in GH-deficient dwarf rats and in age-matched controls. In dwarf rats, serum IGF-1 levels were reduced by 50%, and grow rate was 50% less than normal littermates, although no differences in myocardial IGF-1 messenger RNA levels were observed compared with controls. All rats underwent transthoracic echocardiography at baseline, 2 weeks, and 6 weeks after myocardial infarction. Left ventricular end-diastolic pressure was obtained by in vivo closed chest catheterization. At 6 weeks, both infarcted groups exhibited similar myocardial infarction size at transthoracic echocardiography and at morphometric histology. In both groups with myocardial infarction, there was significant left ventricular dilation and reduced systolic function. However, the extent of remodeling as assessed by the increase in end-diastolic dimension (%Delta + 36 +/- 5 vs. +19 +/- 4; P: < 0.01) and depression of function (%Delta fractional shortening -12 +/- 2 vs. -7 +/- 1; P: < 0.01) were both greater in the dwarf group. Furthermore, dwarf rats failed to develop compensatory hypertrophy of noninfarcted posterior wall (%Delta posterior wall +5 +/- 1 vs. +15 +/- 3; P: < 0.01). Therefore, pathologic left ventricular remodeling and functional loss following myocardial infarction is more marked in conditions of GH deficiency. An intact GH/IGF-1 axis appears necessary for a normal response to myocardial infarction injury in the rat.
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Hormônio do Crescimento/fisiologia , Fator de Crescimento Insulin-Like I/fisiologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/metabolismo , Animais , Diástole , Nanismo/genética , Feminino , Hormônio do Crescimento/deficiência , Fator de Crescimento Insulin-Like I/genética , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Miocárdio/citologia , Miocárdio/patologia , Doenças da Hipófise/genética , RNA Mensageiro/genética , Ratos , Ratos Endogâmicos Lew , Ratos Mutantes , Valores de Referência , Sístole , Função Ventricular Esquerda/fisiologiaRESUMO
To evaluate GH's role in cardiac physiology and its interrelationship with the beta-adrenergic system, we studied GH-deficient dwarf (dw/dw) and control rats in 4 groups of 20 each: dwarf group receiving placebo, dwarf-GH group receiving 2 mg/kg GH, dwarf-GH-propranolol group receiving 2 mg/kg GH and 750 mg/liter propranolol, and a control group of Lewis rats receiving placebo. Dwarf rats showed reduced left ventricular weight and myocyte cross-sectional area, and impaired cardiac performance in vitro. Left ventricular pressure-volume curves showed a shift upward and leftward, indicating reduced distensibility. These abnormalities reversed after GH treatment regardless of concomitant propranolol administration. Although isoproterenol responsiveness was reduced in dwarf rats, there were no differences in beta-adrenergic receptor density, affinity, Na+,K+-adenosine triphosphatase activity, or adenylyl cyclase activity. In summary, myocyte size, cardiac structure, myocardial contractility, and distensibility are abnormal in GH deficiency. The effects of GH are not mediated by the beta-adrenergic pathway, which, in turn, is unaffected by changes in the GH-insulin-like growth factor I axis. Thus, GH plays a regulatory role in normal cardiac physiology that is independent of the beta-adrenergic system.