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1.
Nature ; 583(7815): 211-214, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32641814

RESUMO

The discovery of a radioactively powered kilonova associated with the binary neutron-star merger GW170817 remains the only confirmed electromagnetic counterpart to a gravitational-wave event1,2. Observations of the late-time electromagnetic emission, however, do not agree with the expectations from standard neutron-star merger models. Although the large measured ejecta mass3,4 could be explained by a progenitor system that is asymmetric in terms of the stellar component masses (that is, with a mass ratio q of 0.7 to 0.8)5, the known Galactic population of merging double neutron-star systems (that is, those that will coalesce within billions of years or less) has until now consisted only of nearly equal-mass (q > 0.9) binaries6. The pulsar PSR J1913+1102 is a double system in a five-hour, low-eccentricity (0.09) orbit, with an orbital separation of 1.8 solar radii7, and the two neutron stars are predicted to coalesce in [Formula: see text] million years owing to gravitational-wave emission. Here we report that the masses of the pulsar and the companion neutron star, as measured by a dedicated pulsar timing campaign, are 1.62 ± 0.03 and 1.27 ± 0.03 solar masses, respectively. With a measured mass ratio of q = 0.78 ± 0.03, this is the most asymmetric merging system reported so far. On the basis of this detection, our population synthesis analysis implies that such asymmetric binaries represent between 2 and 30 per cent (90 per cent confidence) of the total population of merging binaries. The coalescence of a member of this population offers a possible explanation for the anomalous properties of GW170817, including the observed kilonova emission from that event.

2.
Am J Hypertens ; 33(3): 243-251, 2020 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-31730171

RESUMO

BACKGROUND: Studies have shown that self-monitoring of blood pressure (BP) is effective when combined with co-interventions, but its efficacy varies in the presence of some co-morbidities. This study examined whether self-monitoring can reduce clinic BP in patients with hypertension-related co-morbidity. METHODS: A systematic review was conducted of articles published in Medline, Embase, and the Cochrane Library up to January 2018. Randomized controlled trials of self-monitoring of BP were selected and individual patient data (IPD) were requested. Contributing studies were prospectively categorized by whether they examined a low/high-intensity co-intervention. Change in BP and likelihood of uncontrolled BP at 12 months were examined according to number and type of hypertension-related co-morbidity in a one-stage IPD meta-analysis. RESULTS: A total of 22 trials were eligible, 16 of which were able to provide IPD for the primary outcome, including 6,522 (89%) participants with follow-up data. Self-monitoring was associated with reduced clinic systolic BP compared to usual care at 12-month follow-up, regardless of the number of hypertension-related co-morbidities (-3.12 mm Hg, [95% confidence intervals -4.78, -1.46 mm Hg]; P value for interaction with number of morbidities = 0.260). Intense interventions were more effective than low-intensity interventions in patients with obesity (P < 0.001 for all outcomes), and possibly stroke (P < 0.004 for BP control outcome only), but this effect was not observed in patients with coronary heart disease, diabetes, or chronic kidney disease. CONCLUSIONS: Self-monitoring lowers BP regardless of the number of hypertension-related co-morbidities, but may only be effective in conditions such obesity or stroke when combined with high-intensity co-interventions.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea , Hipertensão/diagnóstico , Hipertensão/terapia , Autocuidado , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Multimorbidade , Valor Preditivo dos Testes , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Fatores de Tempo
3.
Nature ; 553(7687): 182-185, 2018 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-29323297

RESUMO

Fast radio bursts are millisecond-duration, extragalactic radio flashes of unknown physical origin. The only known repeating fast radio burst source-FRB 121102-has been localized to a star-forming region in a dwarf galaxy at redshift 0.193 and is spatially coincident with a compact, persistent radio source. The origin of the bursts, the nature of the persistent source and the properties of the local environment are still unclear. Here we report observations of FRB 121102 that show almost 100 per cent linearly polarized emission at a very high and variable Faraday rotation measure in the source frame (varying from +1.46 × 105 radians per square metre to +1.33 × 105 radians per square metre at epochs separated by seven months) and narrow (below 30 microseconds) temporal structure. The large and variable rotation measure demonstrates that FRB 121102 is in an extreme and dynamic magneto-ionic environment, and the short durations of the bursts suggest a neutron star origin. Such large rotation measures have hitherto been observed only in the vicinities of massive black holes (larger than about 10,000 solar masses). Indeed, the properties of the persistent radio source are compatible with those of a low-luminosity, accreting massive black hole. The bursts may therefore come from a neutron star in such an environment or could be explained by other models, such as a highly magnetized wind nebula or supernova remnant surrounding a young neutron star.

4.
Nature ; 541(7635): 58-61, 2017 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-28054614

RESUMO

Fast radio bursts are astronomical radio flashes of unknown physical nature with durations of milliseconds. Their dispersive arrival times suggest an extragalactic origin and imply radio luminosities that are orders of magnitude larger than those of all known short-duration radio transients. So far all fast radio bursts have been detected with large single-dish telescopes with arcminute localizations, and attempts to identify their counterparts (source or host galaxy) have relied on the contemporaneous variability of field sources or the presence of peculiar field stars or galaxies. These attempts have not resulted in an unambiguous association with a host or multi-wavelength counterpart. Here we report the subarcsecond localization of the fast radio burst FRB 121102, the only known repeating burst source, using high-time-resolution radio interferometric observations that directly image the bursts. Our precise localization reveals that FRB 121102 originates within 100 milliarcseconds of a faint 180-microJansky persistent radio source with a continuum spectrum that is consistent with non-thermal emission, and a faint (twenty-fifth magnitude) optical counterpart. The flux density of the persistent radio source varies by around ten per cent on day timescales, and very long baseline radio interferometry yields an angular size of less than 1.7 milliarcseconds. Our observations are inconsistent with the fast radio burst having a Galactic origin or its source being located within a prominent star-forming galaxy. Instead, the source appears to be co-located with a low-luminosity active galactic nucleus or a previously unknown type of extragalactic source. Localization and identification of a host or counterpart has been essential to understanding the origins and physics of other kinds of transient events, including gamma-ray bursts and tidal disruption events. However, if other fast radio bursts have similarly faint radio and optical counterparts, our findings imply that direct subarcsecond localizations may be the only way to provide reliable associations.

5.
Nature ; 531(7593): 202-5, 2016 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-26934226

RESUMO

Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

6.
Nature ; 505(7484): 520-4, 2014 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-24390352

RESUMO

Gravitationally bound three-body systems have been studied for hundreds of years and are common in our Galaxy. They show complex orbital interactions, which can constrain the compositions, masses and interior structures of the bodies and test theories of gravity, if sufficiently precise measurements are available. A triple system containing a radio pulsar could provide such measurements, but the only previously known such system, PSR B1620-26 (refs 7, 8; with a millisecond pulsar, a white dwarf, and a planetary-mass object in an orbit of several decades), shows only weak interactions. Here we report precision timing and multiwavelength observations of PSR J0337+1715, a millisecond pulsar in a hierarchical triple system with two other stars. Strong gravitational interactions are apparent and provide the masses of the pulsar M[Symbol: see text](1.4378(13), where M[Symbol: see text]is the solar mass and the parentheses contain the uncertainty in the final decimal places) and the two white dwarf companions (0.19751(15)M[Symbol: see text] and 0.4101(3))M[Symbol: see text], as well as the inclinations of the orbits (both about 39.2°). The unexpectedly coplanar and nearly circular orbits indicate a complex and exotic evolutionary past that differs from those of known stellar systems. The gravitational field of the outer white dwarf strongly accelerates the inner binary containing the neutron star, and the system will thus provide an ideal laboratory in which to test the strong equivalence principle of general relativity.

7.
Science ; 329(5997): 1305, 2010 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-20705813

RESUMO

Einstein@Home aggregates the computer power of hundreds of thousands of volunteers from 192 countries to mine large data sets. It has now found a 40.8-hertz isolated pulsar in radio survey data from the Arecibo Observatory taken in February 2007. Additional timing observations indicate that this pulsar is likely a disrupted recycled pulsar. PSR J2007+2722's pulse profile is remarkably wide with emission over almost the entire spin period; the pulsar likely has closely aligned magnetic and spin axes. The massive computing power provided by volunteers should enable many more such discoveries.

8.
Science ; 318(5851): 777-80, 2007 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-17901298

RESUMO

Pulsar surveys offer a rare opportunity to monitor the radio sky for impulsive burst-like events with millisecond durations. We analyzed archival survey data and found a 30-jansky dispersed burst, less than 5 milliseconds in duration, located 3 degrees from the Small Magellanic Cloud. The burst properties argue against a physical association with our Galaxy or the Small Magellanic Cloud. Current models for the free electron content in the universe imply that the burst is less than 1 gigaparsec distant. No further bursts were seen in 90 hours of additional observations, which implies that it was a singular event such as a supernova or coalescence of relativistic objects. Hundreds of similar events could occur every day and, if detected, could serve as cosmological probes.

9.
Science ; 314(5796): 97-102, 2006 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-16973838

RESUMO

The double pulsar system PSR J0737-3039A/B is unique in that both neutron stars are detectable as radio pulsars. They are also known to have much higher mean orbital velocities and accelerations than those of other binary pulsars. The system is therefore a good candidate for testing Einstein's theory of general relativity and alternative theories of gravity in the strong-field regime. We report on precision timing observations taken over the 2.5 years since its discovery and present four independent strong-field tests of general relativity. These tests use the theory-independent mass ratio of the two stars. By measuring relativistic corrections to the Keplerian description of the orbital motion, we find that the "post-Keplerian" parameter s agrees with the value predicted by general relativity within an uncertainty of 0.05%, the most precise test yet obtained. We also show that the transverse velocity of the system's center of mass is extremely small. Combined with the system's location near the Sun, this result suggests that future tests of gravitational theories with the double pulsar will supersede the best current solar system tests. It also implies that the second-born pulsar may not have formed through the core collapse of a helium star, as is usually assumed.

10.
Nature ; 439(7078): 817-20, 2006 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-16482150

RESUMO

The radio sky is relatively unexplored for transient signals, although the potential of radio-transient searches is high. This was demonstrated recently by the discovery of a previously unknown type of source, varying on timescales of minutes to hours. Here we report a search for radio sources that vary on much shorter timescales. We found eleven objects characterized by single, dispersed bursts having durations between 2 and 30 ms. The average time intervals between bursts range from 4 min to 3 h with radio emission typically detectable for <1 s per day. From an analysis of the burst arrival times, we have identified periodicities in the range 0.4-7 s for ten of the eleven sources, suggesting origins in rotating neutron stars. Despite the small number of sources detected at present, their ephemeral nature implies a total Galactic population significantly exceeding that of the regularly pulsing radio pulsars. Five of the ten sources have periods >4 s, and the rate of change of the pulse period has been measured for three of them; for one source, we have inferred a high magnetic field strength of 5 x 10(13) G. This suggests that the new population is related to other classes of isolated neutron stars observed at X-ray and gamma-ray wavelengths.

11.
Nature ; 434(7037): 1104-6, 2005 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-15858566

RESUMO

Soft gamma-ray repeaters (SGRs) are 'magnetars', a small class of slowly spinning neutron stars with extreme surface magnetic fields, B approximately 10(15) gauss (refs 1 , 2 -3). On 27 December 2004, a giant flare was detected from the magnetar SGR 1806-20 (ref. 2), only the third such event recorded. This burst of energy was detected by a variety of instruments and even caused an ionospheric disturbance in the Earth's upper atmosphere that was recorded around the globe. Here we report the detection of a fading radio afterglow produced by this outburst, with a luminosity 500 times larger than the only other detection of a similar source. From day 6 to day 19 after the flare from SGR 1806-20, a resolved, linearly polarized, radio nebula was seen, expanding at approximately a quarter of the speed of light. To create this nebula, at least 4 x 10(43) ergs of energy must have been emitted by the giant flare in the form of magnetic fields and relativistic particles.

12.
Science ; 303(5661): 1153-7, 2004 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-14716022

RESUMO

The clocklike properties of pulsars moving in the gravitational fields of their unseen neutron-star companions have allowed unique tests of general relativity and provided evidence for gravitational radiation. We report here the detection of the 2.8-second pulsar J0737-3039B as the companion to the 23-millisecond pulsar J0737-3039A in a highly relativistic double neutron star system, allowing unprecedented tests of fundamental gravitational physics. We observed a short eclipse of J0737-3039A by J0737-3039B and orbital modulation of the flux density and the pulse shape of J0737-3039B, probably because of the influence of J0737-3039A's energy flux on its magnetosphere. These effects will allow us to probe magneto-ionic properties of a pulsar magnetosphere.

13.
Nature ; 426(6966): 531-3, 2003 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-14654834

RESUMO

The merger of close binary systems containing two neutron stars should produce a burst of gravitational waves, as predicted by the theory of general relativity. A reliable estimate of the double-neutron-star merger rate in the Galaxy is crucial in order to predict whether current gravity wave detectors will be successful in detecting such bursts. Present estimates of this rate are rather low, because we know of only a few double-neutron-star binaries with merger times less than the age of the Universe. Here we report the discovery of a 22-ms pulsar, PSR J0737-3039, which is a member of a highly relativistic double-neutron-star binary with an orbital period of 2.4 hours. This system will merge in about 85 Myr, a time much shorter than for any other known neutron-star binary. Together with the relatively low radio luminosity of PSR J0737-3039, this timescale implies an order-of-magnitude increase in the predicted merger rate for double-neutron-star systems in our Galaxy (and in the rest of the Universe).

14.
Carbohydr Res ; 336(1): 63-74, 2001 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-11675027

RESUMO

A simple analytical procedure using FT-NIR and multivariate techniques for the rapid determination of individual sugars in fruit juices was evaluated. Different NIR detection devices and sample preparation methods were tested by using model solutions to determine their analytical performance. Aqueous solutions of sugar mixtures (glucose, fructose, and sucrose; 0-8% w/v) were used to develop a calibration model. Direct measurements were made by transflection using a reflectance accessory, by transmittance using a 0.5-mm cell, and by reflectance using a fiberglass paper filter. FT-NIR spectral data were transformed to the second derivative. Partial least-squares regression (PLSR) was used to create calibration models that were cross-validated (leave-one-out approach). The prediction ability of the models was evaluated on fruit juices and compared with HPLC and standard enzymatic techniques. The PLSR loading spectra showed characteristic absorption bands for the different sugars. Models generated from transmittance spectra gave the best performance with standard error of prediction (SEP) <0.10% and R(2) of 99.9% that accurately and precisely predicted the sugar levels in juices, whereas lower precision was obtained with models generated from reflectance spectra. FT-NIR spectroscopy allowed for the rapid ( approximately 3 min analysis time), accurate and non-destructive analysis of sugars in juices and could be applied in quality control of beverages or to monitor for adulteration or contamination.


Assuntos
Bebidas/análise , Carboidratos/análise , Frutas , Bebidas/normas , Calibragem , Frutose/análise , Glucose/análise , Padrões de Referência , Reprodutibilidade dos Testes , Espectroscopia de Infravermelho com Transformada de Fourier/instrumentação , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Sacarose/análise , Fatores de Tempo
15.
Am J Geriatr Cardiol ; 10(5): 269-73, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11528286

RESUMO

Habitual exercise provides numerous health benefits to the older adult. While dynamic aerobic activities increase stamina and lung capacity, isometric or resistance training improves muscle strength and endurance. Long-term benefits of continued exercise include a decreased risk of death from heart disease, enhanced balance and mobility, a decreased risk of diabetes, and an improvement in depressive symptoms. While the hazards of exercise relate predominantly to extremes of intensity and duration, all older adults should consult with a physician before beginning a new activity program. A prescription for exercise should include both aerobic and resistance training components, and frequent follow-up to improve adherence is highly recommended.


Assuntos
Exercício Físico/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , American Heart Association , Bibliografias como Assunto , Pressão Sanguínea/fisiologia , Guias como Assunto , Frequência Cardíaca/fisiologia , Humanos , Pessoa de Meia-Idade , Estados Unidos
16.
Geriatrics ; 56(6): 45-9; quiz 50, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11417374

RESUMO

The normal aging heart undergoes pathophysiologic changes that over time undermine cardiac structure and function. In older persons, declining cardiac function can be accelerated or exacerbated by chronic diseases such as hypertension or heart failure. The convergence of normal alterations and distinct cardiovascular conditions--disorders of rhythm, disorders of the organ itself, and vascular disease--compound the challenge of clinical management. This task is becoming somewhat less complex as new information emerges from clinical studies seeking more effective approaches to preventing and managing myocardial infarction, coronary artery disease, chronic heart failure, and systolic and diastolic dysfunction.


Assuntos
Envelhecimento/fisiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/terapia , Avaliação Geriátrica , Idoso , Idoso de 80 Anos ou mais , Angioplastia Coronária com Balão/métodos , Cardiotônicos/administração & dosagem , Doenças Cardiovasculares/epidemiologia , Feminino , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Humanos , Incidência , Masculino , Prevenção Primária/métodos , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida
17.
JAMA ; 285(21): 2736-42, 2001 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-11386929

RESUMO

CONTEXT: Hip fracture is a common clinical problem that leads to considerable mortality and disability. A need exists for a practical means to monitor and improve outcomes, including function, for patients with hip fracture. OBJECTIVES: To identify and compare the importance of significant prefracture predictors of functional status and mortality at 6 months for patients hospitalized with hip fracture and to compare risk-adjusted outcomes for hospitals providing initial care. DESIGN: Prospective study with data obtained from medical records and through structured interviews with patients and proxies. SETTING AND PARTICIPANTS: A total of 571 adults aged 50 years or older with hip fracture who were admitted to 4 New York, NY, metropolitan hospitals between August 1997 and August 1998. MAIN OUTCOME MEASURES: In-hospital and 6-month mortality; locomotion at 6 months; and adverse outcomes at 6 months, defined as death or needing assistance to ambulate, compared by hospital, adjusting for patient risk factors. RESULTS: The in-hospital mortality rate was 1.6%. At 6 months, the mortality rate was 13.5%, and another 12.8% needed total assistance to ambulate. Laboratory values were strong predictors of mortality but were not significantly associated with locomotion. Age and prefracture residence at a nursing home were significant predictors of locomotion (P =.02 for both) but were not significantly associated with mortality. Adjustment for baseline characteristics either substantially augmented or diminished interhospital differences in outcomes. Two hospitals had 1 outcome (functional status or mortality) that was significantly worse than the overall mean while the other outcome was nonsignificantly better than average. CONCLUSIONS: Mortality and functional status ideally should be considered both together and individually to distinguish effects limited to one or the other outcome. Hospital performance for these 2 measures may differ substantially after adjustment, probably because different processes of care are important to each outcome.


Assuntos
Fraturas do Quadril/terapia , Avaliação de Resultados em Cuidados de Saúde , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Feminino , Mortalidade Hospitalar , Hospitalização , Hospitais Urbanos , Humanos , Modelos Lineares , Locomoção , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Modelos de Riscos Proporcionais , Estudos Prospectivos , Recuperação de Função Fisiológica , Fatores de Risco , Análise de Sobrevida
18.
J AOAC Int ; 84(2): 486-92, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11324615

RESUMO

A peer-verified, gas chromatographic (GC) method is presented for the identification of hydrolyzed inulin syrup (HIS) and high-fructose corn syrup (HFCS) in apple juice. The procedure involves determining the Brix value of the apple juice or apple juice concentrate and preparing a dilution of the test sample to 5.5 degrees Brix. A 100 microL aliquot of the 5.5 degrees Brix test solution is then freeze-dried in a GC autosampler vial. The sugars in the freeze-dried residue are converted to trimethylsilyl derivatives, by the addition of an appropriate silylation reagent, and the vial is heated at 75 degrees C for 30 min. After derivatization, the solution is introduced into a gas chromatograph where the analytes are separated on a 30 m, 0.25 mm id DB-5 column. The method can use hydrogen, helium, or nitrogen as the carrier gas. The analytes and marker compounds are measured by use of a flame ionization detecone of the 2 syrups at 2 levels. Dilution was ascertained by the presence of retrograde sugar markers found in the 2 sugar syrups. All 3 laboratories involved in the study were able to identify the correct diluent in the blind, randomly coded, apple juice test portions. The levels of dilution in the test portions were 0, 6.9% (HIS), 16.0% (HIS), 8.1% (HFCS), and 17.0% (HFCS). No false positive results were reported. Quantitative conclusions can be drawn when the same syrup is used for dilution and as a reference standard.


Assuntos
Bebidas/análise , Inulina/análise , Rosales/química , Zea mays/química , Cromatografia Gasosa , Hidrólise , Indicadores e Reagentes , Controle de Qualidade , Padrões de Referência , Reprodutibilidade dos Testes
19.
J Ocul Pharmacol Ther ; 17(5): 421-32, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11765147

RESUMO

Travoprost is the isopropyl ester prodrug of a high affinity, selective FP prostaglandin full receptor agonist. In contrast to travoprost acid's high affinity and efficacy at the FP receptor, there is only sub-micromolar affinity for the DP, EP1, EP3, EP4, IP, and TP receptors. Travoprost produced a lower incidence of ocular irritation than PGF20 isopropyl ester at a dose of 1 microg in the New Zealand albino (NZA) rabbit. Topical ocular application of travoprost produced a marked miotic effect in cats following doses of 0.01, 0.03 and 0.1 microg. In the ocular hypertensive monkey, b.i.d. application of 0.1 and 0.3 microg of travoprost afforded peak reduction in intraocular pressure (IOP) of 22.7% and 28.6%, respectively. Topical application of travoprost was well tolerated in rabbits, cats and monkeys, causing no ocular irritation or discomfort at doses up to 1 microg. Travoprost is a promising ocular hypotensive prostaglandin FP derivative that has the ocular hypotensive efficacy of PGF2alpha isopropyl ester but with less severe ocular side effects.


Assuntos
Anti-Hipertensivos/farmacologia , Cloprostenol/farmacologia , Receptores de Prostaglandina/agonistas , Adenilil Ciclases/metabolismo , Administração Tópica , Animais , Gatos , Bovinos , Cloprostenol/análogos & derivados , Corpo Lúteo/metabolismo , Dinoprosta/metabolismo , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Feminino , Fibroblastos/efeitos dos fármacos , Humanos , Pressão Intraocular/efeitos dos fármacos , Macaca , Camundongos , Hipertensão Ocular/tratamento farmacológico , Soluções Oftálmicas , Fosfatidilinositóis/metabolismo , Coelhos , Malha Trabecular/efeitos dos fármacos , Travoprost
20.
Exp Eye Res ; 73(6): 815-25, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11846512

RESUMO

AL-3037A (Sodium ferri ethylenediaminetetraacetate), a novel compound shown to stimulate the degradation of glycosaminoglycans, was evaluated for its effects on aqueous humor outflow and intraocular pressure (IOP) in four experimental models. Its effect on outflow facility was assessed in bovine and human ocular perfusion organ cultures. Its IOP effect was tested in normotensive and dexamethasone-induced ocular hypertensive rabbits. In bovine eyes, perfusion with AL-3037A (0.1% w/v, 2.3 m M) significantly increased the outflow facility well above the normal 'wash-out' effect. At 30 min after perfusion, the outflow facility of drug-treated eyes increased by 26.0+/-2.8% (mean +/- S.E.(M.), n = 8), significantly higher than the 12.1 +/- 2.8% increase in vehicle-treated eyes. This difference sustained throughout the study period (2 hr). The compound also enhanced aqueous outflow in perfused human anterior segments. In non-glaucomatous eyes, it produced a small decrease in IOP (15.4 +/- 4.6%, n = 17), but in tissues derived from glaucoma patients, bolus administration of 3 mg (7 micromol) of AL-3037A lowered the IOP by 52-68% (n = 2) lasting for at least 3 hr. This outflow-enhancing effect of AL-3037A in ex vivo studies was confirmed by in vivo results. In normotensive rabbits, oral (50 mg kg(-1)), intravenous (10 mg kg(-1)), or topical (2 mg; 50 microl of 4% w/v solution) administration of AL-3037A produced maximum reduction of IOP, when compared to vehicle-treated animals, by 34.7+/-3.5% (n = 10), 22.0 +/- 4.6% (n = 10), and 21.6 +/-4.5% (n = 10), respectively. In dexamethasone induced ocular hypertensive rabbits, topical application of the compound (0.5 mg; 25 microl of 2% w/v solution) reduced IOP significantly by 19.2+/- 0.4% (n = 7) at 3 hr after dosing. Importantly, the IOP lowering effect of AL-3037A did not diminish even after repeated treatments in consecutive days. Thus, in the four study models across three animal species, AL-3037A was demonstrated to be an efficacious ocular hypotensive compound whose effect is most likely mediated by augmentation of the aqueous outflow. Its proposed action on the metabolism of glycosaminoglycans may provide a new and unique mechanism for the treatment of glaucoma.


Assuntos
Humor Aquoso/efeitos dos fármacos , Pressão Intraocular/efeitos dos fármacos , Animais , Bovinos , Compostos Férricos/farmacologia , Glaucoma/tratamento farmacológico , Humanos , Microscopia Eletrônica/métodos , Hipertensão Ocular/tratamento farmacológico , Técnicas de Cultura de Órgãos , Coelhos
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