RESUMO
STUDY OBJECTIVES: To examine and compare the efficacy and safety of salmeterol xinafoate, a long-acting inhaled beta2-adrenergic agonist, with inhaled ipratropium bromide and inhaled placebo in patients with COPD. DESIGN: A stratified, randomized, double-blind, double-dummy, placebo-controlled, parallel group clinical trial. SETTING: Multiple sites at clinics and university medical centers throughout the United States. PATIENTS: Four hundred eleven symptomatic patients with COPD with FEV1 < or = 65% predicted and no clinically significant concurrent disease. INTERVENTIONS: Comparison of inhaled salmeterol (42 microg twice daily), inhaled ipratropium bromide (36 microg four times a day), and inhaled placebo (2 puffs four times a day) over 12 weeks. RESULTS: Salmeterol xinafoate was significantly (p < 0.0001) better than placebo and ipratropium in improving lung function at the recommended doses over the 12-week trial. Both salmeterol and ipratropium reduced dyspnea related to activities of daily living compared with placebo; this improvement was associated with reduced use of supplemental albuterol. Analyses of time to first COPD exacerbation revealed salmeterol to be superior to placebo and ipratropium (p < 0.05). Adverse effects were similar among the three treatments. CONCLUSIONS: These collective data support the use of salmeterol as first-line bronchodilator therapy for the long-term treatment of airflow obstruction in patients with COPD.
Assuntos
Agonistas Adrenérgicos beta/administração & dosagem , Albuterol/análogos & derivados , Broncodilatadores/administração & dosagem , Pneumopatias Obstrutivas/tratamento farmacológico , Administração por Inalação , Agonistas Adrenérgicos beta/efeitos adversos , Albuterol/administração & dosagem , Albuterol/efeitos adversos , Broncodilatadores/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Feminino , Volume Expiratório Forçado , Humanos , Ipratrópio/administração & dosagem , Pneumopatias Obstrutivas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Xinafoato de Salmeterol , Capacidade VitalRESUMO
Cytokines active on eosinophils are important in the pathogenesis of allergic diseases. A study was conducted to determine if nasal eosinophilia in allergic rhinitis is associated with an increase in eosinophil-active cytokines in nasal secretions and to compare the effects of fluticasone propionate aqueous nasal spray with astemizole and placebo on the levels of these cytokines. Forty-five patients with moderately severe ragweed allergic rhinitis were randomly assigned to receive 2 weeks of treatment with fluticasone propionate aqueous nasal spray 200 micrograms once daily, astemizole 10 mg once daily, or placebo. Nasal lavage was performed in July (preseason), August (peak season), September (after 2 weeks of treatment), and October (postseason). The number of eosinophils, the amount of eosinophil-derived neurotoxin (EDN), and the amount of eosinophil survival-enhancing activity were measured. Total mean nasal symptom scores, concentrations of nasal eosinophils and EDN, and eosinophil survival-enhancing cytokine activity in nasal secretions were significantly lower after 2 weeks of treatment with fluticasone propionate compared with astemizole or placebo. Survival-enhancing activity was detected in the nasal secretions of 25 patients. By blocking activity with monoclonal antibodies, specific cytokines were identified (granulocyte macrophage-colony stimulating factor, 3 samples; interleukin-3, 2 samples; interleukin-5, 5 samples). In conclusion, eosinophil-active cytokine concentrations parallel the nasal symptoms of patients with ragweed allergic rhinitis. Unlike astemizole, fluticasone propionate significantly lowers cytokine activity in nasal tissue, which may contribute to the therapeutic efficacy of the drug.
Assuntos
Androstadienos/administração & dosagem , Antialérgicos/administração & dosagem , Eosinófilos/efeitos dos fármacos , Mucosa Nasal/efeitos dos fármacos , Rinite Alérgica Sazonal/tratamento farmacológico , Ribonucleases , Adulto , Aerossóis , Astemizol/administração & dosagem , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Neurotoxina Derivada de Eosinófilo , Feminino , Fluticasona , Humanos , Masculino , Mucosa Nasal/metabolismo , Neurotoxinas/isolamento & purificaçãoRESUMO
ABSTRACT Interactions between CaCl(2), grapefruit peel tissue, Penicillium digitatum, and the yeast antagonist Pichia guilliermondii strain US-7 were investigated. Application of 68 or 136 mM CaCl(2) to grapefruit surface wounds reduced the incidence of green mold caused by Penicillium digitatum by 43 to 52%. In laboratory tests, a cell suspension (10(7) cells/ml) of Pichia guilliermondii containing either 68 or 136 mM CaCl(2) reduced the incidence of green mold from 27 to 3%. In large scale tests, dip application of 136 mM CaCl(2) with US-7 (10(7) cells/ml) significantly decreased the number of wounds infected by Penicillium digitatum. CaCl(2), with or without yeast cells, stimulated ethylene production in grapefruit tissue. Increasing concentrations of CaCl(2) resulted in decreased spore germination and germ tube elongation of Penicillium digitatum. Pectinolytic activity of crude enzyme preparations of Penicillium digitatum was also inhibited by the presence of increasing concentrations of CaCl(2). US-7 exhibited a strong ability to maintain cytosolic Ca(2+) homeostasis at levels that did not exceed 1.4 muM when exposed to 150 mM CaCl(2). On the other hand, strain 114 of Debaryomyces hansenii, which failed to give any protection against infection by Penicillium digitatum, showed reduced capacity to maintain Ca(2+) homeostasis. The effect of calcium in reducing infection of grapefruit wounds by Penicillium digitatum could be due to direct effects on host tissue (making cell walls more resistant to enzymatic degradation) or the pathogen (interfering with spore germination, growth, and inhibition of fungal pectinolytic enzymes). Alternatively, the ability of US-7 to maintain calcium homeostasis may allow it to grow or assist in its competitive ability in a microenvironment that, because of high levels of calcium ions, is inhibitory to growth of the green mold pathogen.
RESUMO
In recent years, both the public and health authorities have become increasingly concerned about the presence of pesticides in our food supply and the environment. As a direct result of this mounting concern, research efforts for the development of alternative methods for the control of postharvest diseases of fruits and vegetables have been intensified. Considerable attention has been placed on assessing the potential of the use of biological antagonists as a viable alternative to the use of synthetic fungicides. Naturally occurring microbial antagonists have been shown to control several rot pathogens on diverse commodities. Such antagonists have various modes of action: antibiosis or competition for nutrients and space or both, induction of resistance in the host tissue, and direct interaction with the pathogen. The commercialization of certain antagonists to control postharvest decay of fruits and vegetables appears to be feasible and may present an alternative to synthetic pesticides.
Assuntos
Antibiose , Contaminação de Alimentos/prevenção & controle , Fungicidas Industriais/efeitos adversos , Doenças das Plantas , Agricultura/métodos , Antibiose/fisiologia , Ecologia , Imunidade Inata/fisiologia , Doenças das Plantas/microbiologiaRESUMO
A rapid assay to determine antifungal activity in plant extracts and essential oils is described. Wells in microtiter plates were loaded with Botrytis cinerea spores and plant extracts or essential oils. Subsequent changes in optical density following spore germination in the wells was measured after 24 h using an automatic microtiter plate reader driven by a software program developed for this purpose. Extracts from 345 plants and 49 essential oils were evaluated for their antifungal activity against B. cinerea. Among 345 plant extracts analyzed, 13 showed high levels of antifungal activity, with species of Allium and Capsicum predominating. Among the 49 essential oils tested, palmarosa (Cymbopogon martini), red thyme (Thymus zygis), cinnamon leaf (Cinnamomum zeylanicum), and clove buds (Eugenia caryophyllata) demonstrated the most antifungal activity against B. cinerea. The most frequently occurring constituents in essential oils showing high antifungal activity were: D-limonene, cineole; ß-myrcene; α-pinene, ß-pinene; and camphor.
RESUMO
In several plant species, certain cold-regulated proteins share unique properties. These proteins are (a) heat stable and (b) hydrophilic and are related to the Group 2 late embryogenesis abundant or dehydrin family of proteins. Our previous work with sibling deciduous and evergreen peach genotypes demonstrated a correlation between the level of accumulation of certain bark proteins and cold-acclimation potential of these tissues. Here we identify a 60-kD bark protein in peach (Prunus persica [L.] Batsch), PCA60 ("peach cold acclimation"), that is accumulated during cold acclimation and is heat stable. Immunological studies indicated that this protein is related to the dehydrin family of proteins and accumulates at much higher levels in the bark tissues of the deciduous genotype than in the evergreen. Amino acid composition indicated that the 60-kD protein has a compositional bias for glycine (24%), glutamic acid/glutamine (11.4%), aspartic acid/asparagine (10%), and threonine (9.6%), contains relatively low levels of aromatic amino acids (phenylalanine and tyrosine), and is rich in hydrophilic amino acids. A novel characteristic of the 60-kD cold-acclimation protein is the presence of a repeating nine-amino acid sequence. A five-amino acid stretch, which is included within this repeating motif, shares striking homology with other cold-regulated proteins and dehydrins.
Assuntos
Aclimatação , Frutas/fisiologia , Proteínas de Plantas/biossíntese , Sequência de Aminoácidos , Aminoácidos/análise , Temperatura Baixa , Sequência Consenso , Estabilidade de Medicamentos , Frutas/genética , Dados de Sequência Molecular , Proteínas de Plantas/química , Proteínas de Plantas/genética , Sequências Repetitivas de Ácido NucleicoRESUMO
Seasonal patterns of proteins and of cold hardiness were characterized in bark and xylem tissues of genetically related (sibling) deciduous and evergreen peach (Prunus persica [L.] Batsch). In contrast with deciduous trees, which entered endodormancy and abscised leaves in the fall, evergreen trees retained their leaves and exhibited shoot elongation under favorable environmental conditions. A successive increase in the cold hardiness of bark and xylem was observed during the fall in both genotypes. This was followed by a subsequent decrease from midwinter to spring. Xylem tissue in both genotypes exhibited deep supercooling and a significant correlation (r = 0.99) between the midpoint of the low-temperature exotherm and the subzero temperature at which 50% injury occurred (assessed by electrolyte leakage) was noted. The maximum hardiness level attained in deciduous trees was more than twofold that of evergreens. Seasonal pattern of proteins from bark and xylem of the sibling genotypes was characterized by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Among other qualitative and quantitative changes, accumulation of a 19-kilodalton polypeptide in the bark of both genotypes was observed during fall followed by a decrease in spring. This polypeptide accumulated to higher levels in the deciduous peach compared with the evergreen. Additionally, a 16-kilodalton protein exhibited the same pattern in deciduous trees but not in the evergreen trees. Both the 19- and a 16-kilodalton bark proteins conform to the criteria of a bark storage protein. The relationship of seasonal changes in protein to cold hardiness and dormancy in these genetically related peach genotypes is discussed.
RESUMO
A cDNA library was created from cold-acclimated bark tissue of peach and selectively probed using an antibody directed against the lysine-rich consensus region of dehydrin proteins. Several clones were thus obtained which had a high degree of sequence similarity to other dehydrin genes. Northern analysis, using clone 5a, indicated that a 1.8 kb transcript was seasonally expressed in sibling deciduous and evergreen genotypes of peach, and also inducible by water deficit in cv. Rio Oso Gem. The evergreen and deciduous genotypes differ significantly in both their ability to cold-acclimate and in the seasonal expression of the dehydrin transcript and protein. In both genotypes, the transcript was maximally expressed during winter and undetectable in May-July. The evergreen genotype (less cold-tolerant), however, displayed transcript accumulation which lagged behind and declined sooner than in the deciduous genotype. Protein expression was similar to transcript expression, however, protein expression in the evergreen genotype lagged considerably behind transcript accumulation in the fall. This indicates that several levels of regulation of dehydrin proteins may exist during cold acclimation. A genomic clone (G10a) was isolated which contained the full-length dehydrin gene, designated ppdhn1. The peach dehydrin gene encodes 472 amino acids with a predicted size of 50,020 Da. The encoded protein (PCA60) contains nine of the lysine-rich repeats characteristic of dehydrins and two DEYGNP motifs at the amino acid terminus. A genomic blot, probed with clone 5a under stringent conditions, indicated that one or two highly homologous genes are present in peach, whereas an additional member was detected under low-stringency conditions. It is suggested that several members of the dehydrin gene family may exist in peach that vary in their relation to ppdhn1.
Assuntos
Frutas/fisiologia , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/biossíntese , Aclimatação , Sequência de Aminoácidos , Sequência de Bases , Temperatura Baixa , Sequência Consenso , Frutas/genética , Biblioteca Gênica , Biblioteca Genômica , Genótipo , Dados de Sequência Molecular , Proteínas de Plantas/química , Proteínas de Plantas/genética , Estações do Ano , Homologia de Sequência de AminoácidosRESUMO
Many studies have shown that correlation between clinical asthma status and asthma-specific quality of life is only weak to moderate. However, this relationship has never been explored to determine whether the weakness is due to noise of measurement or whether quality of life is a distinct component of asthma health status. With a database from three clinical trials (n = 763), factor analysis was used to explore the relationships between quality of life, measured by the Asthma Quality of Life Questionnaire (AQLQ), and conventional measures of asthma clinical status (symptoms, airway calibre and rescue beta2-agonist use). The analysis revealed that although patients with severe, poorly controlled asthma tend to have worse quality of life than milder, well-controlled patients, overall asthma health status has four components (factors): asthma-specific quality of life; airway calibre; daytime symptoms and daytime beta2-agonist use, and night-time symptoms and night-time beta2-agonist use. The clean loading of all 21 outcomes onto four distinct and clinically identifiable factors suggests that, although some weakness of correlation between clinical indices and quality of life may be due to noise of measurement, it is mainly attributable to asthma health status being composed of distinct components.