ABSTRACT
BACKGROUND: In cystic fibrosis (CF) the defective CF transmembrane conductance regulator protein may be responsible for the impaired transport of glutathione (GSH), the first line defense of the lung against oxidative stress. The aim of this single-blind, randomized, placebo-controlled trial was to evaluate the effect of inhaled GSH in patients with CF. METHODS: 54 adult and 51 pediatric patients were randomized to receive inhaled GSH or placebo twice daily for 12 months. RESULTS: Twelve month treatment with inhaled GSH did not achieve our predetermined primary outcome measure of 15% improvement in FEV1%. Only in patients with moderate lung disease, 3, 6 and 9 months therapy with GSH resulted in a statistically significant increase of FEV1 values from the baseline. Moreover GSH therapy improved 6-minute walking test in pediatric population. GSH was well tolerated by all patients. CONCLUSIONS: Inhaled GSH has slight positive effects in CF patients with moderate lung disease warranting further study. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01450267; URL: www.clinicaltrialsgov.
Subject(s)
Biological Transport/drug effects , Cystic Fibrosis , Glutathione , Lung , Administration, Inhalation , Adolescent , Adult , Antioxidants/administration & dosage , Antioxidants/pharmacokinetics , Child , Cystic Fibrosis/drug therapy , Cystic Fibrosis/metabolism , Drug Monitoring/methods , Exercise Test/drug effects , Female , Forced Expiratory Volume/drug effects , Glutathione/administration & dosage , Glutathione/pharmacokinetics , Humans , Lung/drug effects , Lung/metabolism , Male , Oxidative Stress/drug effects , Severity of Illness Index , Single-Blind Method , Treatment OutcomeABSTRACT
Se realizó un estudio descriptivo transversal de una muestra de 46 arterias de la pierna (tibiales) obtenidas quirúrgicamente de los sujetos amputados en el Servicio de Angiología del Hospital Provincial Manuel Ascunce Domenech en el período de enero de 1998 a enero de 2001. Nuestro objetivo general fue caracterizar la arteriopatía periférica en sujetos diabéticos y no diabéticos. La media aritmética y la desviación estándar de las variables relativas y ponderativas en los sujetos diabéticos estaban muy por encima de las halladas en los sujetos no diabéticos (AU)
Was made a cross-sectional descriptive study of a sample of 46 arteries of the leg (tibials) surgically obtained of the amputated subjects in the Service of Angiology of the Hospital Provincial Manuel Ascunce Domenech in the period of january of 1998 to january of 2001. Our general mission was to characterize the peripheral arteriopathy in diabetic and non-diabetic subjects. The average arithmetic and the standard deviation of the relative and ponderatives variables in the diabetic subjects were very over the found ones in the non-diabetic subjects (AU)
Subject(s)
Humans , Atherosclerosis/epidemiology , Peripheral Vascular Diseases/epidemiology , Epidemiology, Descriptive , Amputation, Surgical , Diabetes Complications/epidemiology , Diabetic Angiopathies/epidemiology , Risk FactorsABSTRACT
Exons 2-9 of KIR3DL3 alleles were characterized by genomic DNA sequencing in two families and in 78 bone marrow transplant samples. Several strategies were used to isolate single alleles for characterization and to resolve alternative allele combinations. We describe 17 novel 3DL3 alleles carried by 30 individuals. Compared with the most closely matched alleles, the new alleles differ by from one to three nucleotides and from zero to three amino acids. The majority of the substitutions were shared with other 3DL3 alleles although three novel polymorphic codons, 151 (exon 4), 327 (exon 7) and 352 (exon 9), are described. Of the 36 different 3DL3 alleles detected in the transplant population, the three most common alleles accounting for 47% of the total were KIR3DL3*00101 (13.5%), KIR3DL3*003 (21.2%) and KIR3DL3*00901 (12.2%).
Subject(s)
Alleles , Genetic Variation , Polymorphism, Genetic , Receptors, KIR/genetics , Amino Acid Substitution , B-Lymphocytes , Cell Line , HumansABSTRACT
DNA enrichment by allele-specific hybridization (DEASH) was used as a means to isolate individual alleles of the killer cell immunoglobulin-like receptor (KIR2DL4) gene from heterozygous genomic DNA. Using long-template polymerase chain reaction (LT-PCR), the complete KIR2DL4 gene was amplified from a cell line that had previously been characterized for its KIR gene content by PCR using sequence-specific primers (PCR-SSP). The whole gene amplicons were sequenced and we identified two heterozygous positions in accordance with the predictions of the PCR-SSP. The amplicons were then hybridized to allele-specific, biotinylated oligonucleotide probes and through binding to streptavidin-coated beads, the targeted alleles were enriched. A second PCR amplified only the exonic regions of the enriched allele, and these were then sequenced in full. We show DEASH to be capable of enriching single alleles from a heterozygous PCR product, and through sequencing the enriched DNA, we are able to produce complete coding sequences of the KIR2DL4 alleles in accordance with the typing predicted by PCR-SSP.
Subject(s)
DNA/genetics , DNA/isolation & purification , Receptors, Immunologic/genetics , Alleles , Base Sequence , Humans , Magnetics , Nucleic Acid Hybridization/methods , Oligonucleotide Probes/genetics , Polymerase Chain Reaction/methods , Receptors, KIR , Receptors, KIR2DL4ABSTRACT
Se realiza un estudio a 572 pacientes que acuden por primera vez a consulta de Angiologia en el hospital provincial docente "Manuel Ascunce Domenech", durante el ano 1981. Se encuentra predominio del sexo femenino y mayor incidencia de patologias venosas. Se destaca la sexta y septima decada de la vida como las mas afectadas por enfermedades vasculares. Se dan a conocer los resultados estadisticos de la procedencia de los pacientes segun sus areas de salud, asi como la indicacion de examenes complementarios
Subject(s)
Adult , Middle Aged , Humans , Male , Female , Vascular Diseases , Ambulatory Care , MorbidityABSTRACT
Se realiza un estudio a 572 pacientes que acuden por primera vez a consulta de Angiologia en el hospital provincial docente "Manuel Ascunce Domenech", durante el ano 1981. Se encuentra predominio del sexo femenino y mayor incidencia de patologias venosas. Se destaca la sexta y septima decada de la vida como las mas afectadas por enfermedades vasculares. Se dan a conocer los resultados estadisticos de la procedencia de los pacientes segun sus areas de salud, asi como la indicacion de examenes complementarios
