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2.
Lancet Psychiatry ; 11(4): 295-302, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38242143

RESUMO

Attempts to understand psychosis-the experience of profoundly altered perceptions and beliefs-raise questions about how the brain models the world. Standard predictive coding approaches suggest that it does so by minimising mismatches between incoming sensory evidence and predictions. By adjusting predictions, we converge iteratively on a best guess of the nature of the reality. Recent arguments have shown that a modified version of this framework-hybrid predictive coding-provides a better model of how healthy agents make inferences about external reality. We suggest that this more comprehensive model gives us a richer understanding of psychosis compared with standard predictive coding accounts. In this Personal View, we briefly describe the hybrid predictive coding model and show how it offers a more comprehensive account of the phenomenology of delusions, thereby providing a potentially powerful new framework for computational psychiatric approaches to psychosis. We also make suggestions for future work that could be important in formalising this novel perspective.


Assuntos
Delusões , Transtornos Psicóticos , Humanos , Delusões/psicologia , Transtornos Psicóticos/psicologia , Cognição
3.
Psychophysiology ; 60(3): e14183, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36219506

RESUMO

This article aimed to synthesize the various triggers of the diving response and to perform a meta-analysis assessing their effects on cardiac vagal activity. The protocol was preregistered on PROSPERO (CRD42021231419; 01.07.2021). A systematic and meta-analytic review of cardiac vagal activity was conducted, indexed with the root mean square of successive differences (RMSSD) in the context of the diving response. The search on MEDLINE (via PubMed), Web of Science, ProQuest and PsycNet was finalized on November 6th, 2021. Studies with human participants were considered, measuring RMSSD pre- and during and/or post-exposure to at least one trigger of the diving response. Seventeen papers (n = 311) met inclusion criteria. Triggers examined include face immersion or cooling, SCUBA diving, and total body immersion into water. Compared to resting conditions, a significant moderate to large positive effect was found for RMSSD during exposure (Hedges' g = 0.59, 95% CI 0.36 to 0.82, p < .001), but not post-exposure (g = 0.11, 95% CI -0.14 to 0.36, p = .34). Among the considered moderators, total body immersion had a significantly larger effect than forehead cooling (QM  = 23.46, df = 1, p < .001). No further differences were detected. Limitations were the small number of studies included, heterogenous triggers, few participants and low quality of evidence. Further research is needed to investigate the role of cardiac sympathetic activity and of the moderators.


Assuntos
Mergulho , Humanos , Mergulho/fisiologia , Frequência Cardíaca/fisiologia , Nervo Vago/fisiologia
4.
J Synchrotron Radiat ; 29(Pt 4): 957-968, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35787561

RESUMO

The newly constructed time-resolved atomic, molecular and optical science instrument (TMO) is configured to take full advantage of both linear accelerators at SLAC National Accelerator Laboratory, the copper accelerator operating at a repetition rate of 120 Hz providing high per-pulse energy as well as the superconducting accelerator operating at a repetition rate of about 1 MHz providing high average intensity. Both accelerators power a soft X-ray free-electron laser with the new variable-gap undulator section. With this flexible light source, TMO supports many experimental techniques not previously available at LCLS and will have two X-ray beam focus spots in line. Thereby, TMO supports atomic, molecular and optical, strong-field and nonlinear science and will also host a designated new dynamic reaction microscope with a sub-micrometer X-ray focus spot. The flexible instrument design is optimized for studying ultrafast electronic and molecular phenomena and can take full advantage of the sub-femtosecond soft X-ray pulse generation program.

5.
Scand J Med Sci Sports ; 29(3): 360-368, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30480353

RESUMO

Type 2 diabetes is associated with microvascular dysfunction, but little is known about how capillary ultrastructure is affected by exercise training. To investigate the effect of two types of exercise training on skeletal muscle capillary ultrastructure and capillarization in individuals with type 2 diabetes, 21 individuals with type 2 diabetes were allocated (randomized controlled trial) to 11 weeks of aerobic exercise training consisting of either moderate-intensity endurance training (END; n = 10) or low-volume high-intensity interval training (HIIT; n = 11). Skeletal muscle biopsies (m vastus lateralis) were obtained before and after the training intervention. At baseline, there was no difference in capillarization, capillary structure, and exercise hyperemia between the two groups. After the training intervention, capillary-to-fiber ratio increased by 8% ± 3% in the END group (P < 0.05) and was unchanged in the HIIT group with no difference between groups. Endothelium thickness increased (P < 0.05), basement membrane thickness decreased (P < 0.05), and the capillary lumen tended (P = 0.07) to increase in the END group, whereas these structural indicators were unchanged after HIIT. In contrast, skeletal muscle endothelial nitric oxide synthase (eNOS) increased after HIIT (P < 0.05), but not END, whereas there was no change in vascular endothelial growth factor (VEGF), superoxide dismutase (SOD)-2, or NADPH oxidase after both training protocols. In contrast to END training, HIIT did not alter capillarization or capillary structure in individuals with type 2 diabetes. In conclusion, HIIT appears to be a less effective strategy to treat capillary rarefaction and reduce basement thickening in type 2 diabetes.


Assuntos
Capilares/ultraestrutura , Diabetes Mellitus Tipo 2/terapia , Exercício Físico , Músculo Esquelético/irrigação sanguínea , Idoso , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Treinamento Intervalado de Alta Intensidade , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo III/metabolismo , Fluxo Sanguíneo Regional , Superóxido Dismutase/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
6.
J Cardiopulm Rehabil Prev ; 38(3): 175-181, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29351130

RESUMO

PURPOSE: Cardiorespiratory fitness is positively related to heart failure (HF) prognosis, but lack of time and low energy are barriers for adherence to exercise. We, therefore, compared the effect of low-volume time-based resistance exercise training (TRE) with aerobic moderate-intensity cycling (AMC) on maximal and submaximal exercise capacity, health-related quality of life, and vascular function. METHODS: Twenty-eight HF patients (New York Heart Association class I-II) performed AMC (n = 14) or TRE (n = 14). Maximal and submaximal exercise capacity, health-related quality of life, and vascular function were evaluated before and after a 6-wk training intervention with 3 training sessions per week. The AMC group and the TRE group trained for 45 and 25 min per training session, respectively. During the training sessions, the TRE and AMC groups trained at 60 ± 4% and 59 ± 2% (mean ± standard deviation) of (Equation is included in full-text article.)O2peak, respectively. RESULTS: The energy expenditure was significantly greater in AMC than in TRE (P < .05). The (Equation is included in full-text article.)O2peak and Wattpeak increased in AMC group (P < .001) and TRE group (P = .001), with no differences between groups. Six-minute walk distance also increased in both groups (AMC, P = .006 and TRE, P = .036), with no difference between groups. Health-related quality of life improved equally in the 2 groups, whereas vascular function did not change in either group. CONCLUSION: These results demonstrate that AMC and TRE equally improved exercise capacity and health-related quality of life in lower New York Heart Association-stage HF patients, despite less time required as well as lower energy expenditure during TRE than during AMC. Therefore, TRE might represent a time-efficient exercise modality for improving adherence to exercise in patients with class I-II HF.


Assuntos
Aptidão Cardiorrespiratória , Treino Aeróbico/métodos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/reabilitação , Treinamento Resistido/métodos , Idoso , Pesquisa Comparativa da Efetividade , Endotélio/fisiopatologia , Metabolismo Energético , Exercício Físico/fisiologia , Tolerância ao Exercício , Feminino , Artéria Femoral/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Qualidade de Vida , Fluxo Sanguíneo Regional , Vasodilatação , Teste de Caminhada
7.
Int J Chron Obstruct Pulmon Dis ; 11: 2659-2669, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27822028

RESUMO

INTRODUCTION: Exercise is an important countermeasure to limb muscle dysfunction in COPD. The two major training modalities in COPD rehabilitation, endurance training (ET) and resistance training (RT), may both be efficient in improving muscle strength, exercise capacity, and health-related quality of life, but the effects on quadriceps muscle characteristics have not been thoroughly described. METHODS: Thirty COPD patients (forced expiratory volume in 1 second: 56% of predicted, standard deviation [SD] 14) were randomized to 8 weeks of ET or RT. Vastus lateralis muscle biopsies were obtained before and after the training intervention to assess muscle morphology and metabolic and angiogenic factors. Symptom burden, exercise capacity (6-minute walking and cycle ergometer tests), and vascular function were also assessed. RESULTS: Both training modalities improved symptom burden and exercise capacity with no difference between the two groups. The mean (SD) proportion of glycolytic type IIa muscle fibers was reduced after ET (from 48% [SD 11] to 42% [SD 10], P<0.05), whereas there was no significant change in muscle fiber distribution with RT. There was no effect of either training modality on muscle capillarization, angiogenic factors, or vascular function. After ET the muscle protein content of phosphofructokinase was reduced (P<0.05) and the citrate synthase content tended increase (P=0.08) but no change was observed after RT. CONCLUSION: Although both ET and RT improve symptoms and exercise capacity, ET induces a more oxidative quadriceps muscle phenotype, counteracting muscle dysfunction in COPD.


Assuntos
Tolerância ao Exercício , Pulmão/fisiopatologia , Força Muscular , Resistência Física , Doença Pulmonar Obstrutiva Crônica/terapia , Músculo Quadríceps/fisiopatologia , Treinamento Resistido , Idoso , Capilares/fisiopatologia , Dinamarca , Metabolismo Energético , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Fisiológica , Oxirredução , Fenótipo , Projetos Piloto , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Músculo Quadríceps/irrigação sanguínea , Músculo Quadríceps/metabolismo , Recuperação de Função Fisiológica , Fluxo Sanguíneo Regional , Fatores de Tempo , Resultado do Tratamento , Capacidade Vital , Teste de Caminhada
8.
J Synchrotron Radiat ; 22(5): 1170-81, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26289268

RESUMO

To cover a large photon energy range, the length of an X-ray mirror is often longer than the beam footprint length for much of the applicable energy range. To limit thermal deformation of such a water-cooled X-ray mirror, a technique using side cooling with a cooled length shorter than the beam footprint length is proposed. This cooling length can be optimized by using finite-element analysis. For the Kirkpatrick-Baez (KB) mirrors at LCLS-II, the thermal deformation can be reduced by a factor of up to 30, compared with full-length cooling. Furthermore, a second, alternative technique, based on a similar principle is presented: using a long, single-length cooling block on each side of the mirror and adding electric heaters between the cooling blocks and the mirror substrate. The electric heaters consist of a number of cells, located along the mirror length. The total effective length of the electric heater can then be adjusted by choosing which cells to energize, using electric power supplies. The residual height error can be minimized to 0.02 nm RMS by using optimal heater parameters (length and power density). Compared with a case without heaters, this residual height error is reduced by a factor of up to 45. The residual height error in the LCLS-II KB mirrors, due to free-electron laser beam heat load, can be reduced by a factor of ∼11 below the requirement. The proposed techniques are also effective in reducing thermal slope errors and are, therefore, applicable to white beam mirrors in synchrotron radiation beamlines.

11.
J Physiol ; 591(20): 5047-59, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-23878368

RESUMO

Ageing is thought to be associated with decreased vascular function partly due to oxidative stress. Resveratrol is a polyphenol, which in animal studies has been shown to decrease atherosclerosis, and improve cardiovascular health and physical capacity, in part through its effects on Sirtuin 1 signalling and through an improved antioxidant capacity. We tested the hypothesis that resveratrol supplementation enhances training-induced improvements in cardiovascular health parameters in aged men. Twenty-seven healthy physically inactive aged men (age: 65 ± 1 years; body mass index: 25.4 ± 0.7 kg m(-2); mean arterial pressure (MAP): 95.8 ± 2.2 mmHg; maximal oxygen uptake: 2488 ± 72 ml O2 min(-1)) were randomized into 8 weeks of either daily intake of either 250 mg trans-resveratrol (n = 14) or of placebo (n = 13) concomitant with high-intensity exercise training. Exercise training led to a 45% greater (P < 0.05) increase in maximal oxygen uptake in the placebo group than in the resveratrol group and to a decrease in MAP in the placebo group only (-4.8 ± 1.7 mmHg; P < 0.05). The interstitial level of vasodilator prostacyclin was lower in the resveratrol than in the placebo group after training (980 ± 90 vs. 1174 ± 121 pg ml(-1); P < 0.02) and muscle thromboxane synthase was higher in the resveratrol group after training (P < 0.05). Resveratrol administration also abolished the positive effects of exercise on low-density lipoprotein, total cholesterol/high-density lipoprotein ratio and triglyceride concentrations in blood (P < 0.05). Resveratrol did not alter the effect of exercise training on the atherosclerosis marker vascular cell adhesion molecule 1 (VCAM-1). Sirtuin 1 protein levels were not affected by resveratrol supplementation. These findings indicate that, whereas exercise training effectively improves several cardiovascular health parameters in aged men, concomitant resveratrol supplementation can blunt these effects.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Exercício Físico , Estilbenos/farmacologia , Idoso , Sistema Cardiovascular/metabolismo , LDL-Colesterol/sangue , Método Duplo-Cego , Epoprostenol/metabolismo , Humanos , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Consumo de Oxigênio , Resveratrol , Comportamento Sedentário , Tromboxano-A Sintase/metabolismo , Triglicerídeos/sangue , Molécula 1 de Adesão de Célula Vascular/metabolismo
12.
Phys Rev Lett ; 105(4): 043003, 2010 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-20867841

RESUMO

The Linac Coherent Light Source is an x-ray free-electron laser that recently demonstrated lasing in the 1.5-15 Å wavelength range. We report on luminescence measurements of a molecular nitrogen gas irradiated by ∼2 mJ, 80 fs x-ray pulses at energies of 0.83, 2.7, and 8.3 keV. These results provide a direct test of our current understanding of photoabsorption, electron dynamics, and fluorescence processes for such intense, ultrashort x-ray pulses. At 0.83 keV, the duration of the fluorescence signal depends strongly on space-charge effects. At 8.3 keV, space-charge effects are weak, and the signal duration is determined by the Auger electron dynamics.

13.
Gynecol Endocrinol ; 26(3): 230-5, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19718567

RESUMO

OBJECTIVE: Pain symptoms in endometriosis patients do not necessarily correlate with the extent of the disease, and there is little evidence regarding the recurrence risk. Aim of this study was to assess the risk factors for the recurrence of endometriosis, with regard to preoperative and postoperative pain. DESIGN: Retrospective observational study. SETTING: Single institution study. POPULATION: A total of 150 patients were followed up for recurrence after surgical treatment for endometriosis. METHODS: The patients were interviewed retrospectively to obtain information about pain levels during the course of the disease. MAIN OUTCOME MEASURES: Disease free survival. RESULTS: High preoperative pain levels were associated with a higher risk of recurrence after 4 years of follow-up. The hazards ratio was 2.30 (95% CI, 1.22-4.31; p = 0.009). None of the other parameters assessed for medical history, reproductive history, or lifestyle was associated with the recurrence risk. CONCLUSIONS: The risk for recurrence after surgery for endometriosis may be substantially influenced by the patients' perception of pain. Risk classifications for the recurrence risk in endometriosis are nonexistent. Developing these is imperatively needed soon to improve further treatment and/or prophylaxis for patients after surgery. A classification might be improved by adding sensory testing before surgery.


Assuntos
Endometriose/patologia , Dor Pélvica/patologia , Doenças Peritoneais/patologia , Adulto , Estudos de Coortes , Intervalo Livre de Doença , Endometriose/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Dor Pélvica/cirurgia , Doenças Peritoneais/cirurgia , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Fatores de Risco
14.
Opt Express ; 17(18): 15508-19, 2009 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-19724548

RESUMO

The first X-ray free electron laser (XFEL) at keV energies will be the Linac Coherent Light Source (LCLS), located at the SLAC National Accelerator Laboratory. Scheduled to begin operation in 2009, this first-of-a-kind X-ray source will produce ultra-short X-ray pulses of unprecedented brightness in the 0.8 to 8 keV first harmonic photon energy regime. Much effort has been invested in predicting and modeling the XFEL photon source properties at the undulator exit; however, as most LCLS experiments are ultimately dependent on the beam focal spot properties it is equally as important to understand the XFEL beam at the endstations where the experiments are performed. Here, we use newly available precision surface metrology data from actual LCLS mirrors combined with a scalar diffraction model to predict the LCLS beam properties in the experiment chambers.

15.
Phys Chem Chem Phys ; 9(30): 3992-8, 2007 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-17646888

RESUMO

This manuscript introduces 7Li{6Li} spin echo double resonance (SEDOR) spectroscopy as a novel approach for studying the spatial distribution of lithium ions in solid electrolytes. Theoretical simulations using density operator theory as well as experimental validation on the model compound lithium carbonate reveal that this method affords a selective measurement of 7Li-6Li heteronuclear dipole-dipole couplings. Dipolar second moments characterizing internuclear lithium-lithium interactions have been measured in lithium silicate (Li2O)(x)(SiO2)(1-x), (0.1 < or = x < or = 0.4) and lithium borate (Li2O)(x)(B2O3)(1-x), (0.1 < or = x < or = 0.3) glasses. The results indicate that the spatial distributions of the lithium ions in these two glass systems are decidedly different. In the lithium silicate glass system, the results give clear evidence of strong cation clustering for x < or = 0.3, providing quantitative support for a previously proposed model of a one-dimensional channel structure. In contrast, in the lithium borate glass system, the cations seem to be more or less randomly distributed. Nevertheless, an observed superlinear dependence of M2(7Li-6Li) as a function of ion concentration indicates subtle changes of the lithium arrangement principles, which are discussed in relation to the previously proposed ring structure of borate glasses.

16.
Eur J Cancer Prev ; 15(6): 474-9, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17106324

RESUMO

The fear of family members of patients with breast or gynaecologic cancer of developing a similar disease is often high. We investigated the acceptance for genetic testing of untested women with a positive family history and their attitude for prophylactic surgery. A total of 659 women with a familial history of breast or gynaecologic cancer were asked to answer a questionnaire regarding their interest in genetic testing for breast cancer as well as for gynaecologic carcinoma and their interest in prophylactic surgery. Genetic testing is seen to be accepted by the majority of participants: 85.0 and 77.8% chose a genetic test for breast and gynaecologic cancer, respectively. Prophylactic surgery was much less chosen; prophylactic mastectomy as well as prophylactic hysterectomy or bilateral prophylactic oophorectomy was an option only for a minority of women. Genetic testing for risk assessment of healthy women with a positive family history was observed to be accepted by a majority of participants. Prophylactic surgery was an option only for a minority and was not acceptable for most of the women.


Assuntos
Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/cirurgia , Testes Genéticos/psicologia , Neoplasias dos Genitais Femininos/prevenção & controle , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Adulto , Atitude Frente a Saúde , Neoplasias da Mama/genética , Neoplasias da Mama/psicologia , Feminino , Predisposição Genética para Doença , Neoplasias dos Genitais Femininos/genética , Neoplasias dos Genitais Femininos/psicologia , Neoplasias dos Genitais Femininos/cirurgia , Humanos , Histerectomia , Mastectomia , Anamnese , Pessoa de Meia-Idade
17.
J Phys Chem B ; 110(29): 14253-61, 2006 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-16854129

RESUMO

Cation-cation interactions are thought to play a significant role in shaping the nonlinear compositional dependence of ionic conductivity, known as the mixed-alkali effect (MAE) in glassy solid electrolytes. For providing a structural rationale of this effect, the discrimination of various cation sites in mixed-alkali glasses is of interest. In the present study, cross-polarization (CP) experiments have been applied to glasses in the system [(Li(2)O)x(Na(2)O)(1-x)](0.3)[B(2)O(3)]0.7 to discriminate between alkali ions by virtue of different heteronuclear (7)Li-(23)Na dipole-dipole coupling strengths. Cross-polarization studies involving two types of quadrupolar nuclei (both (7)Li and (23)Na have a spin-quantum number I = 3/2) are complicated by spin state mixing under radio frequency irradiation and magic-angle spinning (MAS). Therefore careful validation and optimization protocols are reported for the model compound LiNaSO(4) prior to conducting the measurements on the glassy samples. (23)Na -->( 7)Li CP/MAS NMR spectra have been obtained on glasses containing the Na(+) ions as the dilute species. They reveal that those lithium species interacting particularly strongly with sodium ions have the same average (7)Li chemical shift as the entire lithium population; the symmetrical situation applies to the (23)Na nuclei at the sodium rich end of the composition range. On the other hand, a clear site discrimination is afforded by temperature-dependent static (23)Na -->( 7)Li CP experiments, indicating that the Li ions that are most strongly interacting with sodium ions are strongly immobilized. This finding provides the first direct experimental evidence for the proposed secondary mismatch concept invoked for explaining the strong MAE in the dilute foreign ion limit.

18.
Eur J Cancer Prev ; 14(6): 519-24, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16284496

RESUMO

Participation rates in gynaecological cancer screening are influenced by different factors. The knowledge of general and personal risk factors for uterine cancer among women might influence their interest in gynaecological cancer screening. Two thousand nine hundred women in 23 gynaecological outpatient services were invited to answer a structured questionnaire regarding general and personal risk factors for cervical and endometrial carcinoma; 2108 women participated. Women with a history of cancer were excluded from the study. It was found that levels of knowledge about uterine carcinoma were low. Only 47.4% of women knew the difference between the sites of origin of cervical and endometrial cancer. Seventy-seven per cent of participants assessed their knowledge about uterine malignancies as insufficient; 96.3% would appreciate more information about uterine cancer. Younger women were significantly less well informed than postmenopausal women. Known risk factors such as smoking or human papillomavirus (HPV) infection as factors for cervical cancer were underestimated; most women assessed genetic factors as most important for the development of uterine cancer. The level of information about risk factors as well as general facts about gynaecological cancer in women is low. Ameliorating this lack of information might influence the perception of uterine cancer and result in higher participation rates in gynaecological cancer screening.


Assuntos
Conhecimento , Programas de Rastreamento/estatística & dados numéricos , Neoplasias Uterinas/etiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Opinião Pública , Fatores de Risco , Neoplasias Uterinas/diagnóstico
19.
J Mol Cell Cardiol ; 36(4): 539-46, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15081313

RESUMO

Prostaglandin E(1) (PGE(1)) has been used to treat pulmonary hypertension and peripheral artery occlusive disease and has been successfully employed for pharmacological bridging to transplantation in patients with chronic end-stage heart failure. In addition to its vasoactive effects PGE(1) was shown to stimulate angiogenesis in animal models. Recently we showed that PGE(1)-induced angiogenesis in hearts of patients with ischemic heart disease. We proposed that the angiogenic action of PGE(1) is mediated by vascular endothelial growth factor (VEGF). In the present paper we studied a possible effect of PGE(1) on the expression of VEGF-1 in cultured human adult cardiac myocytes (HACM) and cultured human adult cardiac fibroblasts (HACFB), respectively, to identify a cellular source of VEGF-1 in patients treated with PGE(1). We also aimed to delineate mechanisms involved in a possible regulation of VEGF-1 by PGE(1) in these cells. When HACM, isolated from human myocardial tissue, were treated with PGE(1), a significant up to 3-fold increase in VEGF-1 production could be observed. These results could be confirmed on the level of specific mRNA expression as determined by real-time polymerase chain reaction. The effect of PGE(1) on VEGF-1 expression could be blocked by H089, an inhibitor of cAMP-dependent protein kinase A. In HACFB, also isolated from human myocardial tissue, no effect of PGE(1) on VEGF-1 production was seen. If this effect of PGE(1) is also operative in the in vivo situation, one could speculate that cardiac myocytes could be a cellular source of PGE(1)-induced VEGF-1 expression in patients treated with this drug.


Assuntos
Alprostadil/fisiologia , AMP Cíclico/metabolismo , Fibroblastos/metabolismo , Miócitos Cardíacos/metabolismo , Fator A de Crescimento do Endotélio Vascular/biossíntese , Alprostadil/metabolismo , Aorta/citologia , Divisão Celular , Células Cultivadas , Meios de Cultivo Condicionados/farmacologia , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Primers do DNA/química , Relação Dose-Resposta a Droga , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Inibidores Enzimáticos/farmacologia , Humanos , Isoquinolinas/farmacologia , Miócitos Cardíacos/citologia , Neovascularização Patológica , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sulfonamidas/farmacologia , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/metabolismo
20.
Curr Microbiol ; 47(3): 198-202, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14570269

RESUMO

A new and simple method for the purification of extracellular levansucrase from Zymomonas mobilis from highly viscous fermentation broth was developed. After incubation of the fermentation broth with a fructose-polymer cleaving enzyme preparation (Fructozyme, Novozymes, DK) for 48 h, levansucrase precipitated as aggregates and was redissolved in a 3 M urea solution. By ongoing size-exclusion chromatography on Sephacryl S-300 the final levansucrase preparation was purified 100-fold and exhibited a specific activity of 25-35 U/mg(protein). The levansucrase was stable in 3 M urea solution for at least four months without inactivation. To maximize the enzyme yield the dynamic changes of extracellular levansucrase activity during fermentation were investigated. The highest levansucrase activity was observed during the logarithmic phase of growth (15-19 h of fermentation).


Assuntos
Hexosiltransferases/isolamento & purificação , Zymomonas/enzimologia , Centrifugação , Precipitação Química , Cromatografia em Gel , Meios de Cultura/metabolismo , Eletroforese em Gel de Poliacrilamida , Fermentação , Frutanos/metabolismo , Concentração de Íons de Hidrogênio , Peso Molecular , Solubilidade , Sacarose/metabolismo , Ureia , Viscosidade
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