ABSTRACT
El asma es una enfermedad que afecta mas del 5 por ciento de la población de los países industrializados y es un importante problema de salud pública en nuestro país; por lo tanto un tratamiento efectivo es importante para el control de sus síntomas. Para evaluar la efectividad del zileuton; un inhibidor de la enzima 5-lipoxigenasa, se diseñó un estudio doble ciego, randomizado, controlado con placebo. Un total de 25 pacientes con asma y un volumen espiratorio forzado en 1 segundo VEF-1 entre 40 por ciento y 70 por ciento de los valores de predicción y sin tratamiento con glucocorticoides orales ni inhalado; fueron seleccionados a recibir tratamiento con zileuton 600 mg (8 pacientes); zileuton 400 mg (9 pacientes) o placebo (8 pacientes) durante 9 semanas. Las variables estudiadas fueron pruebas de función pulmonar, frecuencia de exacerbaciones de asma que requirieron tratamiento con glucocorticoides, uso de agonistas beta-2 por vía inhalatoria, síntomas asmáticos; la seguridad del tratamiento fue elevada por el monitoreo de efectos adversos. Zileuton produjo un incremento del VEF-1 de 0,37 L. una hora posterior a la administración (p<0.001 vs placebo), equivalente a un incremento del 14,12 por ciento de la línea de la base. Después de 9 semanas, tratamiento con zileuton produjo una mejoría tanto de la función pulmonar como de los síntomas del asma. El incremento mayor fue observado con el grupo que recibió zileuton 600mg. Así, en este grupo el VEF-1 aumentó 0,48 L (2,57 L valor basal a 3,05 L día 64); equivalente a un incremento del 18,67 por ciento (p<0.02), comparado con 0.07 L de aumento del grupo placebo. Los síntomas diurnos y nocturnos, así como la frecuencia en el uso de beta-2 agonista también disminuyeron significativamente con el uso de ambas dosis de zileuton. sólo dos pacientes requirieron tratamiento con glucocorticoides (8 por ciento); uno en el grupo zileuton 400 mg y uno en el grupo placebo. Elevaciones de la transaminansas (tres veces del rango normal) fueron observadas en dos pacientes: uno en el grupo de zileuton 600 mg y otro en el grupo de placebo; ambos pacientes retornaron a valores normales al descontinuar el tratamiento. En conclusión, el tratamiento durante nueve semanas con un inhibidor de la 5-lipoxigenasa, produjo una mejoría significativa en el control del asma, tanto clínica como funcional
Subject(s)
Humans , Male , Female , Asthma , Double-Blind Method , Lipoxygenase Inhibitors , Placebos , Public Health , VenezuelaABSTRACT
[see reaction]. The reaction of activated alkynes with carbonyl compounds in the presence of a catalytic amount of a nucleophile leads to enol-protected functionalized propargyl alcohols and 1,3-dioxolane compounds by way of a mild carbon-carbon bond formation reaction.
ABSTRACT
A Bufo arenarum cellular nucleic acid-binding protein (bCNBP) full-length cDNA was cloned. bCNBP is a 19.4 kDa protein containing seven CCHC zinc finger motifs, an RGG box and a Ser-rich region. Amino acid comparisons showed high values of homology in vertebrates and smaller values in insects or inferior eukaryotes. Northern blot analysis during oogenesis and early development revealed two transcripts with different expressions of pattern behavior. One of them is present in all stages analyzed, whereas the other is only detected from the beginning of zygotic transcription. Immunocytochemistry assays carried out on sections of ovary and early embryos showed that there was no specific staining of previtellogenic oocytes. In early vitellogenic oocytes, in oocytes at stages V/VI and in embryos at early blastula stage, reaction was observed inside the cytoplasm. At mid-blastula stage, CNBP was mainly detected in the epiblast. At the late gastrula stage, two layers of cells were stained in the archenteron roof, in which the internal one presented as strong staining. Nuclei in this layer were stained even stronger than the cytoplasm. Changes in mRNA expression patterns, accompanied by changes in subcellular localization, suggest that CNBP might interact with both nuclear and cytoplasmic nucleic acids.
Subject(s)
DNA-Binding Proteins/biosynthesis , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/genetics , RNA-Binding Proteins , Amino Acid Sequence , Animals , Blotting, Northern , Blotting, Western , Bufonidae , Cell Nucleus/metabolism , Cloning, Molecular , Cytoplasm/metabolism , DNA, Complementary/metabolism , Databases, Factual , Escherichia coli/metabolism , Gene Expression Regulation, Developmental , Immunohistochemistry , Oocytes/metabolism , Oogenesis/physiology , RNA, Messenger/metabolism , Sequence Analysis, DNA , Time Factors , Tissue DistributionABSTRACT
[reaction: see text] A remarkable exo-facial template effect exercised by a 2, 3-O-isopropylidene protective group is the key for the entire 2, 3-trans stereoselectivity observed in the allylsilane addition promoted by BF(3).OEt(2) to 2,3-O-isopropylidene-protected pyrrolidines.
Subject(s)
Pyrrolidines/chemical synthesis , Drug Design , Imines , Indicators and Reagents , Molecular Conformation , Molecular Structure , StereoisomerismABSTRACT
BACKGROUND: Ropivacaine is a new amide local anesthetic, having therapeutic properties similar to those of bupivacaine but with a wider margin of safety. Bupivacaine is probably the most commonly used drug in obstetric epidural analgesia, even though laboratory studies have suggested that pregnancy increases the cardiotoxicity of bupivacaine but not of other local anesthetics. The current study was designed to reevaluate, in a random and blinded fashion, the systemic toxicity of bupivacaine and ropivacaine in nonpregnant and pregnant sheep. METHODS: Chronically prepared nonpregnant and pregnant ewes were randomized to receive an intravenous infusion of ropivacaine or bupivacaine at a constant rate of 0.5 mg.kg-1.min-1 until circulatory collapse. The investigators were blinded to the identity of local anesthetic. Heart rate, arterial blood pressure, and cardiac rhythm were monitored throughout the study. Arterial blood samples were obtained before infusion and at the onset of toxic manifestations, which appeared in the following sequence: convulsions, hypotension, apnea, and circulatory collapse. Serum drug concentrations and protein binding were determined. Blood pH and gas tensions were measured. RESULTS: There were no significant differences between non-pregnant and pregnant animals in the doses or serum concentrations of either drug required to elicit toxic manifestations. In nonpregnant animals, similar doses and serum concentrations of ropivacaine and bupivacaine were associated with the onset of convulsions and circulatory collapse. In pregnant ewes, greater doses of ropivacaine as compared to bupivacaine were required to produce convulsions (7.5 +/- 0.5 vs. 5.0 +/- 0.6 mg.kg-1) and circulatory collapse (12.9 +/- 0.8 vs. 8.5 +/- 1.2 mg.kg-1). The corresponding serum concentrations of ropivacaine were similar to those of bupivacaine. Pregnancy did not affect the serum protein binding of either drug. The proportion of animals manifesting a malignant ventricular arrhythmia as the terminal event was similar among all groups. CONCLUSIONS: The systemic toxicity of ropivacaine or bupivacaine is not enhanced by gestation in sheep. This is in contrast to an earlier study in which the cardiotoxicity of bupivacaine was enhanced during ovine pregnancy. Greater doses of ropivacaine, as compared to bupivacaine, are needed to produce toxic manifestations in pregnant animals.
Subject(s)
Amides/toxicity , Bupivacaine/toxicity , Animals , Apnea/chemically induced , Blood Pressure/drug effects , Dose-Response Relationship, Drug , Double-Blind Method , Female , Heart Rate/drug effects , Hemodynamics/drug effects , Hydrogen-Ion Concentration , Hypotension/chemically induced , Pregnancy/drug effects , Ropivacaine , Seizures/chemically induced , Sheep , Tissue DistributionABSTRACT
A 17-year-old female patient with systemic lupus erythematosus (SLE) developed chronic tophaceous gout, chondrocalcinosis and articular capsule calcification in several joints. Analysis of synovial fluid and tophi revealed the coexistence of monosodium urate, calcium pyrophosphate, hydroxyapatite, and cholesterol crystals.