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1.
Science ; 358(6370): 1570-1574, 2017 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-29038375

RESUMO

On 17 August 2017, gravitational waves (GWs) were detected from a binary neutron star merger, GW170817, along with a coincident short gamma-ray burst, GRB 170817A. An optical transient source, Swope Supernova Survey 17a (SSS17a), was subsequently identified as the counterpart of this event. We present ultraviolet, optical, and infrared light curves of SSS17a extending from 10.9 hours to 18 days postmerger. We constrain the radioactively powered transient resulting from the ejection of neutron-rich material. The fast rise of the light curves, subsequent decay, and rapid color evolution are consistent with multiple ejecta components of differing lanthanide abundance. The late-time light curve indicates that SSS17a produced at least ~0.05 solar masses of heavy elements, demonstrating that neutron star mergers play a role in rapid neutron capture (r-process) nucleosynthesis in the universe.

2.
Br J Clin Pharmacol ; 62(5): 512-26, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17010103

RESUMO

AIM: The aim of this systematic review was to assess the quality and outcomes of clinical trials investigating the effect of St John's wort extracts on the metabolism of drugs by CYP3A. METHODS: Prospective clinical trials assessing the effect of St John's wort (SJW) extracts on metabolism by CYP3A were identified through computer-based searches (from their inception to May 2005) of Medline, Cinahl, PsycINFO, AMED, Current Contents and Embase, hand-searches of bibliographies of relevant papers and consultation with manufacturers and researchers in the field. Two reviewers selected trials for inclusion, independently extracted data and recorded details on study design. RESULTS: Thirty-one studies met the eligibility criteria. More than two-thirds of the studies employed a before-and-after design, less than one-third of the studies used a crossover design, and only three studies were double-blind and placebo controlled. In 12 studies the SJW extract had been assayed, and 14 studies stated the specific SJW extract used. Results from 26 studies, including all of the 19 studies that used high-dose hyperforin extracts (>10 mg day(-1)), had outcomes consistent with CYP3A induction. The three studies using low-dose hyperforin extracts (<4 mg day(-1)) demonstrated no significant effect on CYP3A. CONCLUSION: There is reasonable evidence to suggest that high-dose hyperforin SJW extracts induce CYP3A. More studies are required to determine whether decreased CYP3A induction occurs after low-dose hyperforin extracts. Future studies should adopt study designs with a control phase or control group, identify the specific SJW extract employed and provide quantitative analyses of key constituents.


Assuntos
Citocromo P-450 CYP3A/metabolismo , Interações Ervas-Drogas , Hypericum/metabolismo , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Adulto , Idoso , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
3.
Proc Natl Acad Sci U S A ; 98(26): 14769-72, 2001 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-11742082

RESUMO

Fluorescence superquenching is investigated for polyelectrolytes consisting of cyanine dye pendant polylysines ranging in number of polymer repeat units (N(PRU)) from 1 to 900, both in solution and after adsorption onto silica nanoparticles. As N(PRU) increases, the absorption and fluorescence evolve from monomer spectra to red-shifted features indicative of molecular J aggregates. In solution, the superquenching sensitivity toward an anionic electron acceptor increases by more than a millionfold over the N(PRU) range from 1 to 900. The dramatic increase is attributed to enhanced equilibrium constants for binding the quenchers, and the amplified quenching of a delocalized exciton of approximately 100 polymer repeat units. The self-assembly of monomer onto silica and clay nanoparticles leads to formation of J aggregates, and surface-activated superquenching enhanced 10,000x over the monomer in solution, indicating the formation of "self-assembled polymers" on the nanoparticle surface. Utilization of these self-assembled polymers as high-sensitivity biosensors is demonstrated.


Assuntos
Técnicas Biossensoriais , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Microesferas , Espectrometria de Fluorescência
5.
Proc Natl Acad Sci U S A ; 96(22): 12287-92, 1999 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-10535914

RESUMO

The fluorescence of a polyanionic conjugated polymer can be quenched by extremely low concentrations of cationic electron acceptors in aqueous solutions. We report a greater than million-fold amplification of the sensitivity to fluorescence quenching compared with corresponding "molecular excited states." Using a combination of steady-state and ultrafast spectroscopy, we have established that the dramatic quenching results from weak complex formation [polymer(-)/quencher(+)], followed by ultrafast electron transfer from excitations on the entire polymer chain to the quencher, with a time constant of 650 fs. Because of the weak complex formation, the quenching can be selectively reversed by using a quencher-recognition diad. We have constructed such a diad and demonstrate that the fluorescence is fully recovered on binding between the recognition site and a specific analyte protein. In both solutions and thin films, this reversible fluorescence quenching provides the basis for a new class of highly sensitive biological and chemical sensors.


Assuntos
Técnicas Biossensoriais , Polímeros/química , Fluorescência
6.
Langmuir ; 15(4): 901, 1999 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-27366914
8.
Photochem Photobiol ; 64(6): 923-35, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8972633

RESUMO

A series of novel, unsymmetrically substituted metallo-phthalocyanines was synthesized, along with their symmetrically substituted analogs, and the effects of structure and metal substitution on their photophysical and photoredox properties were investigated. The macrocycles were synthesized using a mixed-condensation method followed by chromatographic separation of the resulting soluble products. They possess a catechol "active site" and three tert-butyl groups for enhanced solubility. The ground- and excited-state photophysical properties of the free-base, Zn(II) and Pd(II) macrocycles were measured and compared with their symmetrically substituted (tetra[tert-butyl]) analogs. The efficiency with which these macrocycles sensitize the formation of singlet oxygen was determined and discussed in the context of the excited-state photophysical properties. Several examples of photoinduced electron transfer reactions with one- and two-electron acceptors are demonstrated and discussed. These soluble molecules can be tuned to optimize their photochemical and redox properties by varying the central metal, axial ligands and other substituents, thereby providing a series of molecules for the investigation of photodynamic therapy and photoinduced electron transfer mechanisms.


Assuntos
Indóis/química , Isoindóis , Metais/química , Fotoquímica
9.
Photochem Photobiol ; 61(1): 90-8, 1995 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7899498

RESUMO

From a structurally distinct set of o-substituted tetraphenylporphyrins, the picket fence porphyrin (PFP), 3,1-meso-tetrakis(o-propionamidophenyl)porphyrin (3,1-TPro) has been selected as a potential candidate for use in the photodynamic therapy (PDT) of cancer. In this report, the time-dependent tissue distribution of 14C-labeled 3,1-TPro is described along with the results of various treatment regimens. The tissue distribution of radiolabeled 3,1-TPro is comparable to that of other porphyrin photosensitizers with the advantage of being most effective at 4 h and being cleared rapidly from most tissues. The results of the various treatment regimen experiments, as well as other studies, indicate that the 3,1-TPro mechanism of action is similar to that of other photosensitizers, but may include some minor differences. The conclusion is that 3,1-TPro and other PFP offer a class of effective photosensitizers that may be exploited for their structural versatility, straightforward synthesis leading to a compound of high purity and known structure, and stability (both in terms of shelf-life and in vivo metabolism) as potential candidates for PDT.


Assuntos
Mesoporfirinas/farmacologia , Fotoquimioterapia , Radiossensibilizantes/farmacologia , Animais , Divisão Celular/efeitos dos fármacos , Feminino , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/patologia , Mesoporfirinas/farmacocinética , Radiossensibilizantes/farmacocinética , Ratos , Ratos Endogâmicos F344 , Distribuição Tecidual
10.
Am J Emerg Med ; 12(2): 185-9, 1994 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8161394

RESUMO

The objective of this study was to examine the use of limited, goal-directed, two-dimensional ultrasound studies performed by emergency physicians and to assess the frequency, variety, and accuracy of their readings. A 1-year prospective study was performed by using an emergency department (ED) ultrasound machine with a 3.5-mHz mechanical oscillating sector transducer and a 5.0-mHz vaginal transducer. In a series of proctoring sessions, radiologists trained emergency physicians to do limited, goal-directed ultrasonography. Laser print ultrasonograms were collected from all ED ultrasound examinations performed during a 1-year period and were compared with either formal ultrasonograms performed in the radiology department, the patient's hospital record, or both. Sensitivity, specificity, and positive predictive value (PPV), as well as negative predictive values (NPV), were calculated. The setting was a 104-bed community hospital with an ED volume of 25,000 patients annually, and patients whom the emergency physician believed needed ultrasound studies in the ED were entered. ED ultrasonography was performed in 167 patients by 14 physicians during a 1-year period. For 132 patients who completed formal follow-up, the overall diagnostic accuracy of interpretations of ED ultrasonograms yielded a sensitivity of .95, specificity of .98, PPV of .99, and NPV of .89. Eleven categories of ultrasound use were reported. The three studies most commonly performed were for gallbladder disease (53%), intrauterine pregnancy (28%), and abdominal aortic aneurysms (7%). Accuracy of ED gallbladder ultrasonograms for 65 patients showed a sensitivity of .86, specificity of .97, PPV of .97, and NPV of .85.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Medicina de Emergência/normas , Serviço Hospitalar de Emergência/normas , Padrões de Prática Médica/estatística & dados numéricos , Ultrassonografia/estatística & dados numéricos , California , Medicina de Emergência/educação , Medicina de Emergência/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitais de Prática de Grupo/normas , Hospitais de Prática de Grupo/estatística & dados numéricos , Humanos , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ultrassonografia/instrumentação , Ultrassonografia/métodos
11.
J Air Med Transp ; 11(5): 7-12, 1992 May.
Artigo em Inglês | MEDLINE | ID: mdl-10118902

RESUMO

If a woman becomes pregnant while on flight status, a potential conflict exists between the needs and desires of the program and those of the flight crew member. Association of Air Medical Services (AAMS) member programs were surveyed to determine the extent of pregnancy policy standards within the air medical profession. A survey was mailed to 150 AAMS program directors in the fall of 1988. The survey was followed with a second mailing and a telephone follow-up for clarification. Replies were received from 110 program directors. Fifty-five percent of those responding noted they had a policy on flight crew member (FCM) pregnancy. Thirty percent noted a date prior to term that the pregnant FCM (PFCM) would be removed from flight status. Seventy percent of the programs noted that they had not previously had a PFCM. Over half of the programs allowed PFCMs to fly until the third trimester, with just under a quarter allowing flights until 38 weeks or greater. There are few articles specifically referring to air medical FCM pregnancy, and policies regarding FCM pregnancy differ widely among the AAMS member programs.


Assuntos
Aeronaves/normas , Serviços Médicos de Emergência/normas , Auxiliares de Emergência/normas , Política Organizacional , Gravidez , Mulheres Trabalhadoras/estatística & dados numéricos , Coleta de Dados , Tomada de Decisões Gerenciais , Serviços Médicos de Emergência/organização & administração , Auxiliares de Emergência/estatística & dados numéricos , Estudos de Avaliação como Assunto , Feminino , Humanos , Estados Unidos
12.
Cancer Res ; 51(7): 1836-45, 1991 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-2004367

RESUMO

A set of structurally distinct o-substituted tetraphenylporphyrins, the picket fence porphyrins, were evaluated for their ability to photosensitize tumor mitochondria in vitro, in vivo-in vitro, and tumor implants in situ. Differential photosensitized inactivation efficiencies toward mitochondrial enzymes in vitro are reported for the 12 compounds studied as a function of side chain length and isomer structure. Fluorescence studies in aqueous solution coupled with mitochondrial uptake studies indicate that the observed range of inactivation efficiencies are due to different inherent solubilization properties for the picket fence porphyrins. Studies with the most soluble compound, 3,1-meso-tetrakis(o-propionamidophenyl)porphyrin, using an in vivo-in vitro protocol indicate that a more effective photosensitization can be obtained by using an interval of 4 h between photosensitizer administration and irradiation as compared to 24 h for Photofrin II. Irradiation of tumors in vivo 4 h following administration of 3,1-meso-tetrakis(o-propionamidophenyl)porphyrin, resulted in a mean tumor doubling time more than eight times longer than that observed for untreated tumors. 31P NMR spectroscopy in situ indicated that photodynamic therapy using 3,1-meso-tetrakis(o-propionamidophenyl)porphyrin induced a rapid and significant reduction in high energy phosphate metabolites.


Assuntos
Neoplasias Mamárias Experimentais/tratamento farmacológico , Mesoporfirinas/farmacologia , Mitocôndrias/enzimologia , Fotoquimioterapia , Animais , Feminino , Neoplasias Mamárias Experimentais/metabolismo , Mesoporfirinas/química , Mesoporfirinas/metabolismo , Mitocôndrias/metabolismo , Ratos , Ratos Endogâmicos F344 , Solubilidade
15.
Cancer Res ; 48(5): 1148-52, 1988 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-2830016

RESUMO

The synthetic "picket fence" porphyrin, tetra(o-acetamidophenyl)porphine (TAc), as a biological photosensitizer has been evaluated both in vitro and in vivo in mitochondria from the R3230AC mammary tumor. Studies in vitro, consisting of incubation of mitochondria with TAc at a concentration of 4.0 micrograms/ml followed by photolysis, result in the inhibition of cytochrome c oxidase, proton translocating ATPase, succinate dehydrogenase, and malate dehydrogenase. The diminution in activity of the first three enzymes is approximately 2-fold greater than that seen with Photofrin II under the same conditions. Although TAc exists as four isolable atropisomers, no differences among these different forms were observed in their photosensitized inhibition of mitochondrial enzymes. Administration to tumor-bearing rats of TAc i.p. at a dose of 25 mg/kg did result in accumulation of porphyrin within the mitochondria of the R3230AC tumor as determined by subsequent irradiation of isolated mitochondria. The potential utility of TAc and related porphyrins in cancer phototherapy is discussed.


Assuntos
Fotoquimioterapia , Porfirinas/farmacologia , Animais , Éter de Diematoporfirina , Complexo IV da Cadeia de Transporte de Elétrons/antagonistas & inibidores , Feminino , Hematoporfirinas/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/enzimologia , Porfirinas/uso terapêutico , Ratos , Ratos Endogâmicos F344 , Relação Estrutura-Atividade , Succinato Desidrogenase/antagonistas & inibidores
16.
Adv Exp Med Biol ; 238: 291-304, 1988.
Artigo em Inglês | MEDLINE | ID: mdl-3250245

RESUMO

The studies cited in this paper demonstrate that the unique environment provided by L. B. films and supported multilayers can produce a variety of molecular effects on photochemical reactivity that can, in turn, result in films, interfaces or surfaces having macroscopic properties which can be modulated by light. Although these investigations have been focused on molecular reactivity in films and how it can be modified (or persist unchanged), the results suggest several possible technological applications which might result from investigations directed more closely to them.


Assuntos
Alcenos/efeitos da radiação , Corantes/efeitos da radiação , Membranas Artificiais , Fluorescência , Isomerismo , Fotoquímica , Radiossensibilizantes , Relação Estrutura-Atividade , Tensoativos
17.
Exp Cell Res ; 168(1): 1-14, 1987 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-3096750

RESUMO

Uptake and metabolism of thymidine and adenosine have been studied in embryos of the sea urchin Strongylocentrotus purpuratus. Uptake of these nucleosides is found to be mutually competitive, with the Km for uptake of thymidine similar to its Ki for inhibition of adenosine uptake and vice versa. The metabolic studies show that adenosine is rapidly and completely phosphorylated upon entry, even at high exogenous concentrations which saturate the uptake mechanism. In contrast, at concentrations which saturate nucleoside uptake, thymidine becomes appreciably catabolized (up to 60%) to thymine and beta-amino-isobutyric acid in addition to its phosphorylation to thymine nucleotides. Negligible amounts of endogenous thymidine appear to remain unmetabolized following uptake in these embryos. The data provide strong in vivo evidence for separate metabolic pathways for thymidine and adenosine which have not previously been described in this organism. The observation of mutual competition during uptake, together with different routes of metabolism for these nucleosides, would suggest that the rate-limiting step in the uptake process is transport rather than metabolism. The specificity of this transport system for its nucleoside substrate has been examined in some detail in the present report. All naturally occurring nucleosides but only a limited number of nucleoside analogs are recognized by this membrane carrier. Neither purine nor pyrimidine bases are substrates for this transport system. Previous work by this laboratory has demonstrated the strict Na+-dependence of this carrier, its high affinity for nucleoside substrate, and its activation at fertilization. These observations and the substrate specificity studies of the present work together describe a unique transport system for nucleosides in sea urchin embryos which is quite different from those previously described in mammalian cells.


Assuntos
Adenosina/metabolismo , Ouriços-do-Mar/embriologia , Timidina/metabolismo , Ácidos Aminoisobutíricos/metabolismo , Animais , Ligação Competitiva , Transporte Biológico , Glutaral/farmacologia , Cinética , Fosforilação , Ouriços-do-Mar/efeitos dos fármacos , Sódio/farmacologia
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