RESUMEN
The cj0183 and cj0588 genes identified in the Campylobacter jejuni NCTC 11168 genome encode proteins with homology to virulence factors found in other bacteria. Previous studies showed that single mutation in the cj0183 gene does not affect adhesion of C. jejuni to the Caco-2 cell line whereas protein encoded by cj0588 is involved in adherence to the Caco-2 cells. In the presented study differences in invasion index were observed between mutants in both genes and single mutation of cj0588 in 81116 and 81-176 C. jejuni strains This fact indicates that Cj0183 protein might play some role in invasion of bacteria into host cells.
Asunto(s)
Proteínas Bacterianas/metabolismo , Campylobacter jejuni/fisiología , Células Epiteliales/microbiología , Regulación Bacteriana de la Expresión Génica/fisiología , Animales , Adhesión Bacteriana/genética , Adhesión Bacteriana/fisiología , Proteínas Bacterianas/genética , Células CACO-2 , Humanos , Microscopía Confocal , MutaciónRESUMEN
Specimens of gastric mucosa of 17 free-ranging wild boars (Sus scrofa) shot in the Central Poland during 2007/2008 hunting season were investigated for the presence of Helicobacter species. Histopathology, Helicobacter genus-specific 16S rRNA PCR, and DNA sequence analysis were employed. In PCR analysis the presence of Helicobacter's DNA was detected in one stomach. Obtained sequence analysis showed its relatedness to Helicobacter heilmannii type 2. In histopathology of the PCR-positive sample the presence of tightly coiled spiral bacteria was detected on the surface of the antral mucosa, in gastric pits and lumen of the upper parts of antral glands. Potential pathologic significance of the presence of Helicobacter in the stomach of free-ranging wild boars was obscured by the parasitic invasion-caused gastritis, and remains unknown.
Asunto(s)
Infecciones por Helicobacter/veterinaria , Helicobacter/aislamiento & purificación , Sus scrofa , Enfermedades de los Porcinos/microbiología , Animales , ADN Bacteriano/clasificación , ADN Bacteriano/aislamiento & purificación , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/microbiología , Polonia/epidemiología , Reacción en Cadena de la Polimerasa/veterinaria , Porcinos , Enfermedades de los Porcinos/epidemiologíaRESUMEN
Vaccines are the most effective prophylactic tool in veterinary medicine. Despite the great success of many vaccines used currently, there is still a constant need for their improvement. An ideal vaccine should contain a variety of immunogens, be safe and efficacious and induce broad humoral and cell-mediated immunity with one or, at most, two administrations given orally rather than by injection, and should be inexpensive. Traditional approaches include attenuated live vaccines, inactivated vaccines and subunit vaccines. Recently, scientific advances in molecular biology, immunology and bioinformatics, as well as the growing number of sequenced genomes of pathogens, have led to significant progress in respect to understanding virulence mechanisms at the molecular level. Genetic engineering has been applied to obtain recombinant bacterial and viral genomes in order to produce a modified and safe product useful in vaccine development. This article presents the progress and novel strategies used in creating new generation vaccines. It focuses on methods of searching for vaccine candidates to construction of vaccines based on recombinant DNA or proteins.
Asunto(s)
Vacunas Sintéticas/inmunología , Administración Oral , Animales , Antígenos Bacterianos , Antígenos Virales , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/inmunología , Ingeniería Genética , Subunidades de Proteína , Vacunas de ADN/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Virales/administración & dosificación , Vacunas Virales/inmunologíaRESUMEN
A total of 69 Campylobacter jejuni and 16 Campylobacter coli strains isolated from chicken, dog and pig stool samples were characterized based on their resistance to five antimicrobial agents and on plasmid pTet profiles. Antimicrobials used in this study were: amoxicillin/clavulanic acid, ciprofloxacin, erythromycin, tetracycline and trimethoprim/sulfamethoxazole. Among the isolates studied, 91.7% were resistant to one or more antimicrobial agent. The highest level of resistance for the whole test group was to trimethoprim/sulfamethoxazole (57.6%), followed by ciprofloxacin (44.2%) and tetracycline (20%). All isolates were susceptible to amoxicillin/clavulanic acid. Strains isolated from chickens were susceptible to erythromycin. Few erythromycin-resistant strains were isolated from dogs and pigs (5.8%). C. coli strains exhibited a higher antibiotic resistance than C. jejuni strains, excluding resistance to trimethoprim/sulfamethoxazole. The pTet plasmid harboring the tet(O) gene was detected in 14 Campylobacter spp. strains. Our studies demonstrate that the majority (71.4%) of tetracycline-resistant isolates carry a plasmid-borne tet(O) gene, particularly strains for which the minimum inhibitory concentration (MIC) are > or = 256 microg/ml. In conclusion, we have found high-level trimethoprim/sulfamethoxazole, ciprofloxacin and tetracycline resistance in Polish strains isolated from different sources. This study has demonstrated that resistance of Campylobacter species differs depending on both the bacterial species and animal origins. All strains that displayed resistance to four antimicrobial agents were isolated from pigs. Localization of the tet(O) gene on either plasmid or chromosome was not found to be correlated with tetracycline resistance.
Asunto(s)
Infecciones por Campylobacter/microbiología , Campylobacter/efectos de los fármacos , Campylobacter/aislamiento & purificación , Enfermedades de los Perros/microbiología , Enfermedades de las Aves de Corral/microbiología , Enfermedades de los Porcinos/microbiología , Animales , Antibacterianos/farmacología , Infecciones por Campylobacter/epidemiología , Pollos , Enzimas de Restricción del ADN , Enfermedades de los Perros/epidemiología , Perros , Farmacorresistencia Bacteriana Múltiple , Pruebas de Sensibilidad Microbiana , Plásmidos , Enfermedades de las Aves de Corral/epidemiología , Porcinos , Enfermedades de los Porcinos/epidemiologíaRESUMEN
A Kazal-type elastase inhibitor was purified by trichloroacetic acid precipitation of sheep lung lavage fluid followed by chymotrypsin affinity and gel-filtration chromatography of the supernatant. Sheep lung elastase inhibitor (SLEI) is glycosylated. Laser desorption mass spectrometry indicated that SLEI has a molecular mass of 16.8-17.3 kDa. Partial protein sequence of SLEI and of a peptide derived from SLEI showed 31-52% and 51-66% homology at the N-terminus and at the inhibitory site respectively with Kazal-type double-headed proteinase inhibitors (bikazins). SLEI inhibited human leukocyte elastase and porcine pancreatic elastase but not human cathepsin G. It was inactivated by chloramine-T and reactivated when incubated with methionine sulfoxide peptide reductase and dithiothreitol, indicating the presence of a methionine at the active site. The concentration of SLEI in bronchoalveolar lavage fluid (BALF) and lung lymph was 0.28 microM (0.23-0.49); 0.24 microM (0.20-0.31) (median, (range), n = 5), respectively and was undetectable in plasma (< 0.03 microM) suggesting that SLEI is produced in the lung. The median molar ratios of SLEI to alpha1-proteinase inhibitor in BALF and lung lymph were 3.2 to 1 and 0.017 to 1, respectively. These results indicate that SLEI probably makes an important contribution to antielastase defence in epithelial lining liquid.
Asunto(s)
Elastasa de Leucocito/antagonistas & inhibidores , Pulmón/fisiología , Inhibidores de Serina Proteinasa/química , Inhibidores de Serina Proteinasa/farmacología , Inhibidor de Tripsina Pancreática de Kazal/aislamiento & purificación , Inhibidor de Tripsina Pancreática de Kazal/farmacología , Secuencia de Aminoácidos , Animales , Carnívoros , Catepsina G , Catepsinas/antagonistas & inhibidores , Cromatografía de Afinidad , Cromatografía en Gel , Quimotripsina , Perros , Zorros , Humanos , Pulmón/química , Visón , Datos de Secuencia Molecular , Peso Molecular , Oxidación-Reducción , Páncreas/enzimología , Elastasa Pancreática/antagonistas & inhibidores , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Serina Endopeptidasas , Inhibidores de Serina Proteinasa/aislamiento & purificación , Ovinos , Porcinos , Irrigación Terapéutica , Inhibidor de Tripsina Pancreática de Kazal/químicaRESUMEN
The volume, velocity, and acceleration of ascending aortic blood were measured in man using a pulsed Doppler ultrasound instrument, with online spectral analysis and offline computer processing of velocity data. This system was firstly validated in a test rig capable of generating pulsatile flow of talc particles in water at physiological velocities and accelerations in a model aorta. Doppler measurements correlated well (r greater than or equal to 0.90) with simultaneous electromagnetic measurements of stroke volume, peak ejection velocity, and maximum acceleration in this rig. In vivo validation was performed firstly by comparing simultaneous Doppler and thermodilution cardiac output (Q) measurements; this yielded the following regression equation: Doppler Q = 0.90 X thermodilution Q + 0.03 litre.min-1, r = 0.92; n = 38. Beat by beat measurements were then validated against simultaneous invasive aortic blood velocity measurements made using a Mills electromagnetic cathetertip probe. When paced single beats of different size were compared within subjects the correlation coefficients between Doppler and electromagnetic measurements averaged 0.89 for stroke volume, 0.91 for peak ejection velocity, and 0.79 for maximum acceleration in five subjects. The absolute values for velocity and acceleration from the Doppler system differed significantly from the absolute values given by the electromagnetic system and this difference was not consistent between subjects. It is concluded that the Doppler system can non-invasively record relative changes in left ventricular ejection in man.
Asunto(s)
Aorta/fisiología , Gasto Cardíaco , Ultrasonografía , Velocidad del Flujo Sanguíneo , Fenómenos Electromagnéticos , Femenino , Humanos , Volumen Sistólico , TermodiluciónRESUMEN
Increased elastinolytic activity has been correlated with the degree of lung damage occurring in a variety of lung diseases including cystic fibrosis; serine proteinase inhibitors are currently on trial for the treatment of some lung disorders. However, human lung lavage cells also secrete metallo-dependent elastases. Here we show, for the first time, that whilst these are readily inhibited by EDTA, inhibition of serine elastases using serpins (serine proteinase inhibitors) is not always possible. This may reflect inactivation of serpins by uninhibited metalloproteinases and oxidants in a low protein milieu. Thus, the therapeutic inhibition of excessive elastinolytic activity may require a combination of inhibitors to work efficiently.
Asunto(s)
Pulmón/enzimología , Elastasa Pancreática/antagonistas & inhibidores , Adulto , Anciano , Líquido del Lavado Bronquioalveolar/citología , Medios de Cultivo Condicionados , Ácido Edético/farmacología , Inhibidores Enzimáticos/farmacología , Humanos , Técnicas In Vitro , Elastasa de Leucocito , Pulmón/citología , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/enzimología , Linfocitos/enzimología , Macrófagos Alveolares/enzimología , Persona de Mediana Edad , Neutrófilos/enzimología , Serpinas/farmacología , alfa 1-Antitripsina/farmacologíaRESUMEN
The physiological function of the lipocortins, proteins which are thought to be glucocorticoid-regulated, is unclear. An improved assay for lipocortins might help to elucidate their role. A rapid and specific sandwich enzyme-linked immunosorbent assay (ELISA) for lipocortin 1 with a working range of 1-2000 ng/ml and an interrun coefficient of variation of less than 10% is described and used in this pilot study to quantify human lipocortin 1 for the first time in acellular bronchoalveolar lavage fluid (BALF), and in media conditioned by BAL cells, from control patients and those with pulmonary sarcoidosis. Using this assay a statistically significant relationship, not previously observed in man, has been demonstrated between concentrations of lipocortin 1/ml of BALF and serum cortisol levels (n = 10, rs = 0.6939, P less than 0.05). Although lipocortin 1 levels in acellular BALF were the same in control and sarcoid patients, significantly more lipocortin 1 was released from sarcoid BAL cells in culture (median 21.6, range 8.1-45.4 ng lipocortin/10(6) cells/h in culture) than from control cells (2.5, 1.5-7.6 ng lipocortin/10(6) cells/h in culture). The possible clinical significance of these data is discussed, but remains to be established.
Asunto(s)
Líquido del Lavado Bronquioalveolar/análisis , Proteínas de Unión al Calcio/análisis , Enfermedades Pulmonares/fisiopatología , Pulmón/análisis , Sarcoidosis/fisiopatología , Anexinas , Western Blotting , Humanos , Hidrocortisona/sangre , Inmunoensayo , Enfermedades Pulmonares/sangre , Sarcoidosis/sangreRESUMEN
This paper summarizes evidence for reflex genioglossus muscle activation by stimuli of negative airway pressure in normal, awake human subjects. Stimuli of negative airway pressure (range -5 to -35 cm H2O) caused activation of the genioglossus muscle. The larger values of negative pressure gave larger responses. Response latencies (median = 34 milliseconds) were much faster than the time for voluntary muscle activation (median = 184 milliseconds), suggesting that the responses were reflex in origin. The reflex nature of the responses was confirmed by studies with local anesthetics. The trigeminal, superior laryngeal and the glossopharyngeal nerves all mediated a component of the responses observed from the upper airway.
Asunto(s)
Presión del Aire , Músculos Faríngeos/inervación , Faringe/fisiología , Reflejo , Vigilia , Electromiografía , Humanos , Faringe/inervación , Ventilación PulmonarRESUMEN
Lipocortins are structurally related, glucocorticoid-inducible proteins that inhibit phospholipase A2 (PLA2), thereby reducing the liberation of arachidonic acid from phospholipids and so limiting the synthesis of eicosanoid inflammatory mediators. This study is the first demonstration of one lipocortin, lipocortin 1 (Lc 1; 37 kDa), in human lung lavage supernatants. In lavage fluid from healthy volunteers, a higher percentage (greater than 70%) of the detected Lc 1 was in its native form, compared to that from patients with abnormal lungs. In patients' lavage fluids, Lc 1 was more likely to be partially degraded (34 kDa). In abnormal bronchoalveolar lavage fluid (BALF), the more polymorphonuclear neutrophils (PMN)/lavage, the lower the proportion of Lc 1 in the native (37 kDa) form (n = 7 pairs, rs = -0.8214, p less than 0.05). Furthermore, when BALF cells were cultured and the harvested conditioned media incubated with pure human recombinant Lc 1, degradation of the 37 kDa form increased with the percentage of PMN (n = 10 pairs, s = -0.7200 after 1 hr; n = 6 pairs, rs = -0.9241 after 6 hr). These results suggest that factors released from the PMN are responsible for Lc 1 degradation in man. When recombinant human Lc 1 was incubated with human neutrophil elastase, the enzyme degraded Lc 1 in a dose-dependent way, suggesting that neutrophil elastase may be one such factor. Since PMNs are ubiquitous at sites of inflammation, it is possible that Lc 1 degradation is a permissive mechanism, which ensures that sufficient inflammation occurs to destroy the provocative stimulus. However, it is equally possible that, in some circumstances, the mechanism may be pathological and that the inactivation of Lc 1 leads to chronic, uncontrolled inflammation.
Asunto(s)
Líquido del Lavado Bronquioalveolar/análisis , Proteínas de Unión al Calcio/análisis , Fosfolipasas/antagonistas & inhibidores , Neumonía/patología , Adulto , Anciano , Anexinas , Western Blotting , Líquido del Lavado Bronquioalveolar/citología , Proteínas de Unión al Calcio/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neutrófilos/análisis , Neutrófilos/fisiología , Neumonía/diagnóstico , Neumonía/fisiopatologíaRESUMEN
Alveolar Type II epithelial cells dedifferentiate rapidly in vitro. Studies with animal tissue suggest that cell-cell and extracellular matrix-cell interactions are important in the retention of Type II cell morphology in vitro. Thus, in this study with human tissue, alveolar Type II cells, alveolar macrophages, and spindle cells were prepared from the same sample of lung (obtained following lobectomy for cancer, n = 3), cocultured on glass cover slips or tissue culture plastic, and studied by light microscopy with scanning (SEM) and transmission (TEM) electron microscopy for 8 days. The primary cell isolates contained approximately 45% Type II cells; the remainder were macrophages or unidentifiable cells. Clusters, made up of a single layer of cuboidal Type II cells around a central core of connective tissue (largely collagen and some elastic tissue), formed above a monolayer of spindle cells. The Type II cells were morphologically similar to those seen in vivo. The cells were still cuboidal at 8 days but had lost their lamellar bodies, which were released into the medium via the apical surface. The clusters increased in size with time (area, microns 2: day 1, 29(5-143) x 10(2); day 8, 63(10-311) x 10(2); mean(range); p less than 0.02) without changing in number per culture, suggesting Type II cell proliferation. This may have been due to factors produced by the other cells and adherence to the extracellular matrix (ECM); (free collagen fibers, present in the original preparation, spindle cells, and/or Type II cells could be responsible for presence of ECM). We propose this as a useful model for the study of human Type II epithelial cells in vitro.
Asunto(s)
Diferenciación Celular , Epitelio/crecimiento & desarrollo , Macrófagos/fisiología , Alveolos Pulmonares/citología , División Celular , Células Cultivadas , Epitelio/fisiología , Epitelio/ultraestructura , Matriz Extracelular/fisiología , Humanos , Técnicas In Vitro , Macrófagos/ultraestructuraRESUMEN
Mast cells were identified by electronmicroscopy in the alveolar wall of the lung in 20 subjects (10 normal, 10 abnormal). A quantitative and qualitative study was made of the mast cells. In the normal lung there was an average concentration of 350 mast cells/mm2 of alveolar wall and in the abnormal 523/mm2. Mast cells occupied approximately 1.6-2.1% of the area of the alveolar wall. There was marked variation in the structure of the mast cell granules but no differences between those in the normal and abnormal lungs. There was evidence that constant degranulation of mast cells may be occurring in the lung. The role that alveolar mast cells may play in the vasoconstrictor response to alveolar hypoxia is discussed. It is suggested that the tachypnoea present in asthma may partly be due to release of mediators from sensitised mast cells within the alveolar wall.
Asunto(s)
Mastocitos/ultraestructura , Alveolos Pulmonares/ultraestructura , Anciano , Neoplasias de los Bronquios/patología , Recuento de Células , Gránulos Citoplasmáticos/ultraestructura , Femenino , Humanos , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Fibrosis Pulmonar/patologíaRESUMEN
To test the role of elastase in the pathogenesis of emphysema human neutrophil elastase (HNE) was localised by electron microscopy using an immunogold staining technique. Specific localisation of HNE to elastic tissue in emphysema did not occur, but non-specific binding of immunoglobulin G (IgG) to elastic tissue in emphysematous and normal lung tissue, which was completely blocked by the non-immune serum that was homologous to the gold labelled second antibody, was found. HNE was also present, however, in the granules of neutrophils in the same sections. Non-specific labelling associated with elastin was probably due to binding of IgG to the high numbers of hydrophobic and charged regions known to be present in this molecule, and it is concluded that our findings do not support the existence of high concentrations of elastase in association with elastin in emphysematous lung tissue.
Asunto(s)
Tejido Elástico/enzimología , Neutrófilos/enzimología , Elastasa Pancreática/metabolismo , Enfisema Pulmonar/enzimología , Anciano , Anciano de 80 o más Años , Tejido Elástico/patología , Femenino , Humanos , Inmunoglobulina G/análisis , Pulmón/enzimología , Pulmón/ultraestructura , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Enfisema Pulmonar/patologíaRESUMEN
Desmosine is an amino acid specific to elastin. Animal studies suggest that urinary desmosine (UD) represents endogenous elastin degradation. Therefore, UD has previously been used to investigate endogenous elastolysis, but was not elevated in subjects with chronic obstructive airways disease (COAD), although accelerated pulmonary elastolysis is thought to contribute to COAD. We have investigated whether this reflects large day-to-day and between-subject variation in UD and whether, in man, dietary desmosine contributes significantly to that in urine. Mean 24-hour UD output (over 5 consecutive days) from 10 asymptomatic subjects (5 males) was higher in males than females (77.4 +/- 9.6 and 40.2 +/- 5.0 nmol/24 hours, respectively; mean +/- SD, P less than .001), but not significantly different when expressed in terms of creatinine (micrograms desmosine/100 mg creatinine: males, 2.5 +/- 0.4; females, 3.1 +/- 0.8; mean +/- SD). The lowest between-subject variation was observed when the mean of 5 days' 24-hour UD values was analyzed on the basis of gender (coefficient of variation [CV], 12.5%); when gender was not considered, the least between-subject variation was found for the mean of 5 days' desmosine/creatinine analysis (CV, 24.5%). Approximately 1% of dietary desmosine (ingested as [3H]elastin and [3H] desmosine) was excreted in the urine within 24 hours, contributing approximately 15% of UD while on a normal diet. Although ingestion of a low elastin diet (less than 1/10 desmosine/24 hours than a normal diet) resulted in lower within-subject variation in 24-hour UD excretion (mean CV decreased from 31.5% to 20.2%), the between-subject CV and UD levels did not alter.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Desmosina/orina , Elastina/metabolismo , Enfermedades Pulmonares/metabolismo , Adulto , Anciano , Desmosina/administración & dosificación , Desmosina/farmacología , Dieta , Femenino , Humanos , Inyecciones Intravenosas , Enfermedades Pulmonares/orina , Masculino , Persona de Mediana Edad , Valores de Referencia , Deficiencia de alfa 1-AntitripsinaRESUMEN
We employed an associative learning paradigm to test the hypothesis that exercise hyperpnea in humans arises from learned responses forged by prior experience. Twelve subjects undertook a "conditioning" and a "nonconditioning" session on separate days, with order of performance counterbalanced among subjects. In both sessions, subjects performed repeated bouts of 6 min of treadmill exercise, each separated by 5 min of rest. The only difference between sessions was that all the second-to-penultimate runs of the conditioning session were performed with added dead space in the breathing circuit. Cardiorespiratory responses during the first and last runs (the "control" and "test" runs) were compared for each session. Steady-state exercise end-tidal PCO(2) was significantly lower (P = 0.003) during test than during control runs for both sessions (dropping by 1.8 +/- 2 and 1.4 +/- 3 Torr during conditioning and nonconditioning sessions, respectively). This and all other test-control run differences tended to be greater during the first session performed regardless of session type. Our data provide no support for the hypothesis implicating associative learning processes in the ventilatory response to exercise in humans.
Asunto(s)
Ejercicio Físico/fisiología , Espacio Muerto Respiratorio/fisiología , Fenómenos Fisiológicos Respiratorios , Adulto , Condicionamiento Clásico , Femenino , Homeostasis , Humanos , Hiperventilación/etiología , MasculinoRESUMEN
The effect of local anesthetic aerosol inhalation on the ventilatory response and the sensation of breathlessness to CO2 rebreathing was studied in seven healthy male subjects with permanent tracheal stomas after laryngectomy for carcinoma. Inhalation of bupivacaine aerosol sufficient to abolish the cough reflex to mechanical probing below the carina increased the ventilatory response to CO2 in six of seven subjects compared with saline control. This was achieved by an increase in both respiratory frequency (f) and tidal volume (VT) in four subjects, f in one subject, and VT in one subject. All subjects reported that they were more breathless on rebreathing after bupivacaine aerosol. The six subjects who recorded breathlessness with a visual analog scale (VAS) indicated its onset at a lower minute ventilation (VE) and gave higher VAS scores for equivalent levels of VE after threshold. We conclude that the enhanced CO2 sensitivity and breathlessness on rebreathing after airway anesthesia results from altered lower airway receptor discharge.
Asunto(s)
Anestesia por Inhalación/efectos adversos , Bupivacaína/efectos adversos , Dióxido de Carbono/fisiología , Disnea/etiología , Hipercapnia/etiología , Laringectomía , Anciano , Volumen Espiratorio Forzado , Capacidad Residual Funcional , Humanos , Masculino , Persona de Mediana Edad , Volumen de Ventilación Pulmonar , Capacidad VitalRESUMEN
The increase in PCO2 that occurs during sleep may reflect an inadequate ventilatory compensation to an increase in upper airway resistance. To address this question in humans, we examined changes in breathing during wakefulness and non-rapid-eye-movement sleep in eight laryngectomized subjects who breathed through a tracheal stoma. In these subjects, any sleep-related increase in upper airway resistance could not affect ventilation. Healthy subjects breathing via an intact upper airway were studied as controls. The mean increase in end-tidal PCO2 from wakefulness to sleep was 2.7 +/- 2.6 (SD) Torr (P = 0.05) in laryngectomized subjects and 1.6 +/- 1.4 Torr (P = 0.02) in control subjects. During wakefulness, ventilation was lower in laryngectomized subjects compared with control subjects, although this difference was not statistically significant (6.8 +/- 1.9 vs. 7.4 +/- 1.2 l/min; P > 0.05). During sleep, the fall in ventilation was similar in the two groups (1.1 +/- 2.1 vs. 0.8 +/- 2.1 l/min; P > 0.05). Our observations are not consistent with the view that increases in upper airway resistance are obligatory for sleep-related CO2 retention in humans.
Asunto(s)
Laringe/fisiología , Mecánica Respiratoria/fisiología , Sueño/fisiología , Vigilia/fisiología , Anciano , Resistencia de las Vías Respiratorias/fisiología , Dióxido de Carbono/sangre , Electroencefalografía , Femenino , Humanos , Hipercapnia/sangre , Laringectomía , Masculino , Persona de Mediana Edad , Pruebas de Función Respiratoria , EspirometríaRESUMEN
We investigated the possible role of an increase in total pulmonary resistance in the sleep-related hypoventilation that occurs in healthy subjects. Eight nonsnoring volunteers were studied during quiet wakefulness and stage IV sleep. Airflow was measured via a nasal mask with a low dead space, and breathing pattern, end-tidal PCO2 (PETCO2), and a continuous estimate of total pulmonary resistance were estimated. From wakefulness to sleep, mean inspiratory resistance increased from 5.5 +/- 2.4 (SD) to 8.1 +/- 4.3 cmH2O.l-1.s, PETCO2 increase from 38.7 +/- 3.0 to 40.7 +/- 3.5 Torr, and ventilation decreased from 7.12 +/- 1.15 to 6.47 +/- 1.68 l/min. In five of the eight subjects, low levels of continuous positive airway pressure were applied during stage IV sleep to reverse any increase in resistance. In these subjects, continuous positive airway pressure reduced mean inspiratory resistance from 9.3 +/- 4.3 +/- 3.0 cmH2O.l-1.s but had little effect on mean PETCO2 (from 39.8 +/- 4.0 to 39.6 +/- 4.0 Torr) and mean ventilation (from 6.79 +/- 1.93 to 6.91 +/- 1.80 l/min). These findings suggest that in nonsnoring subjects reductions in alveolar ventilation cannot be accounted for by an increase in airway resistance.
Asunto(s)
Resistencia de las Vías Respiratorias/fisiología , Hipoventilación/fisiopatología , Pulmón/fisiología , Sueño/fisiología , Ronquido/fisiopatología , Adulto , Computadores , Electroencefalografía , Electrooculografía , Femenino , Humanos , Masculino , Pruebas de Función RespiratoriaRESUMEN
Lipocortin-1 (LC-1; annexin-1) may mediate some anti-inflammatory actions of the glucocorticoids, probably after binding to specific cell surface binding sites. We have quantified LC-1 levels in bronchoalveolar lavage (BAL) fluid and cells collected from seven healthy volunteers before and after 7 days of treatment with an oral glucocorticoid, prednisolone (30 mg/day). Extracellular BAL LC-1 was higher and cellular LC-1 was lower after prednisolone than before [extracellular: before, median 98 ng/mg albumin (range 48-350 ng/mg albumin); after, 236 ng/mg albumin (19-414 ng/mg albumin); P < 0.05. Cellular: before, 23.3 ng/10(6) cells (14.6-26.9 ng/10(6) cells); after, 18.0 ng/10(6) cells (122-268 ng/10(6) cells); P < 0.05]. The distribution of LC-1 within BAL cells ex vivo (cell surface = 25%, cytosol = 50%, membrane = 25%) was unaffected by prednisolone treatment. However, in adherent cells that had been cultured for 4 h, 70-80% of the LC-1 was on the cell surface. In summary, prednisolone appears to promote cellular release of LC-1. The difference in distribution of cellular LC-1 in BAL cells ex vivo and in vitro may reflect adherence and/or activation.
Asunto(s)
Anexina A1/metabolismo , Líquido del Lavado Bronquioalveolar/química , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Prednisolona/farmacología , Adulto , Anexina A1/inmunología , Autoanticuerpos/análisis , Autoanticuerpos/inmunología , Líquido del Lavado Bronquioalveolar/citología , Humanos , Recuento de Leucocitos/efectos de los fármacos , Masculino , Concentración Osmolar , Valores de Referencia , Fracciones Subcelulares/metabolismo , Distribución TisularRESUMEN
Inspiratory activation of the genioglossus (GG) may occur by central drive or as a reflex to negative airway pressure. To distinguish between these, we studied seven laryngectomy patients who breathe via tracheal stomas. Negative pressure stimuli (-15 and -25 cmH2O for 500 ms) were applied 1) at functional residual capacity and 2) during early inspiration via (i) the upper airway (UA) and (ii) the tracheal stoma. Intraoral surface GG electromyogram was quantified, as described previously (R. L. Horner, J. A. Innes, K. Murphy, and A. Guz, J. Physiol. Lond. 436: 15-29, 1991). Phasic GG activity was also measured from an integrated electromyogram during spontaneous and inspiratory loaded breathing. Reflex GG activation occurred with negative UA pressure both at functional residual capacity and during inspiration (P < 0.001), but pressure stimuli at the stoma caused no significant activation (P = 0.07). Phasic inspiratory activation occurred in four patients at rest and in all seven patients during inspiratory loading (P < 0.02). These patients demonstrate 1) reflex activation of the GG by negative UA pressure without airflow or respiratory effort and 2) central inspiratory GG activation that is not mediated by negative airway pressure.