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1.
Transfusion ; 54(8): 2045-54, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24673504

RESUMO

BACKGROUND: Extracellular hemoglobin (Hb)-based oxygen carriers (HBOCs) are under extensive consideration as oxygen therapeutics. Their effects on cellular mechanisms related to apoptosis are of particular interest, because the onset of proapoptotic pathways may give rise to tissue damage. STUDY DESIGN AND METHODS: The objective was to assess whether the properties of the Hb that replaces blood during an isovolemic hemodilution would modulate apoptotic-response mechanisms in rat brain and whether such signaling favors cytoprotection or damage. We exposed rats to exchange transfusion (ET; 50% blood volume and isovolemic replacement with Hextend [negative colloid control], MP4OX [PEGylated HBOC with high oxygen affinity], and ααHb [αα-cross-linked HBOC with low oxygen affinity; n=4-6/group]). Sham rats acted as control. Animals were euthanized at 2, 6, and 12 hours after ET; brain tissue was harvested and processed for analysis. RESULTS: In MP4OX animals, the number of neurons that overexpressed the hypoxia-inducible factor (HIF)-1α was higher than in ααHb, particularly at the early time points. In addition, MP4OX was associated with greater phosphorylation of protein kinase B (Akt), a well-known cytoprotective factor. Indeed, the degree of apoptosis, measured as terminal deoxynucleotidyl transferase-positive neurons and caspase-3 cleavage, ranked in order of MP4OX < Hextend < ααHb. CONCLUSION: Even though both HBOCs showed increased levels of HIF-1α compared to shams or Hextend-treated animals, differences in signaling events resulted in very different outcomes for the two HBOCs. ααHb-treated brain tissue showed significant neuronal damage, measured as apoptosis. This was in stark contrast to the protection seen with MP4OX, apparently due to recruitment of Akt and neuronal specific HIF-1α pathways.


Assuntos
Apoptose/efeitos dos fármacos , Aspirina/análogos & derivados , Substitutos Sanguíneos/farmacologia , Encéfalo/efeitos dos fármacos , Hemoglobinas/farmacologia , Hemorragia/terapia , Derivados de Hidroxietil Amido/farmacologia , Hipóxia Encefálica/prevenção & controle , Maleimidas/farmacologia , Neurônios/efeitos dos fármacos , Oxigênio/sangue , Polietilenoglicóis/farmacologia , Animais , Aspirina/farmacologia , Aspirina/uso terapêutico , Substitutos Sanguíneos/uso terapêutico , Encéfalo/patologia , Hipóxia Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Transfusão Total , Hemodiluição , Hemoglobinas/uso terapêutico , Hemorragia/complicações , Derivados de Hidroxietil Amido/uso terapêutico , Hipóxia Encefálica/etiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Maleimidas/uso terapêutico , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Neurônios/patologia , Polietilenoglicóis/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/biossíntese , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Ratos Sprague-Dawley
2.
J Phys Chem A ; 110(51): 13799-807, 2006 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-17181337

RESUMO

We have undertaken a kinetic study of heterogeneous ozone decomposition on alpha-Fe2O3 (hematite) and alpha-Al2O3 (corundum) aerosols under ambient conditions of temperature, pressure, and relative humidity in order to better understand the role of mineral dust aerosol in ozone loss mechanisms in the atmosphere. The kinetic measurements are made in an environmental aerosol reaction chamber by use of infrared and ultraviolet spectroscopic probes. The apparent heterogeneous uptake coefficient, gamma, for ozone reaction with alpha-Fe2O3 and alpha-Al2O3 surfaces is determined as a function of relative humidity (RH). The uptake of ozone by the iron oxide surface is approximately an order of magnitude larger than that by the aluminum oxide sample, under dry conditions. At the pressures used, alpha-Fe2O3 shows clear evidence for catalytic decomposition of ozone while alpha-Al2O3 appears to saturate at a finite ozone coverage. The measured uptake for both minerals decreases markedly as the RH is increased. Comparison with other literature reports and the atmospheric implications of these results are discussed.


Assuntos
Aerossóis/química , Óxido de Alumínio/química , Compostos Férricos/química , Ozônio/química , Catálise , Poeira , Umidade , Cinética , Ozônio/análise , Pressão , Temperatura
3.
Complement Ther Med ; 14(1): 3-9, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16473748

RESUMO

OBJECTIVES: To investigate the efficacy of a topical wheatgrass cream for improving pain and function in patients with chronic plantar fasciitis. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Eighty participants with chronic plantar fasciitis were randomly assigned to a treatment group (wheatgrass cream) or a control group (placebo cream). All participants applied a cream twice daily for 6 weeks. Follow up was conducted at 6 and 12 weeks. MAIN OUTCOME MEASURES: Visual Analogue Scale (VAS) for daily first-step pain and the Foot Health Status Questionnaire (FHSQ) for overall foot function. Secondary measures of foot posture, calf muscle strength and range of ankle dorsiflexion were also assessed. RESULTS: No significant differences were found between groups with respect to main outcomes of first-step pain or foot function at any time. Both groups improved significantly from baseline to 6 weeks, and these improvements were maintained at 12 weeks. CONCLUSIONS: The topical application of wheatgrass cream is no more effective than a placebo cream for the treatment of chronic plantar fasciitis.


Assuntos
Fasciíte Plantar/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Triticum , Administração Tópica , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Resultado do Tratamento
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