ABSTRACT
Eosinophil is considered to be a main protagonist in asthma; however, often discordances between clinical manifestations and response to treatment are observed. We aimed to determine the occurrence of neutrophil predominance in asthma and to identify its characteristics on the basis of clinical-functional features, induced sputum cellular pattern and soluble molecules, to guide the appropriated anti-inflammatory therapy. A total of 41 patients were included in randomized groups: 21-40 year-old, with stable mild-to-severe asthma, steroid-naïve and non-smokers. An induced sputum sample was obtained under basal conditions, a second one after treatment with budesonide (400 µg b.i.d.) or montelukast (10 mg/d) for six weeks, and a final one after a 4-week washout period. By cytospin we evaluated eosinophil (EP) or neutrophil predominance (NP), and in supernatant we determined LTE4, and CC16. Peak expiratory flow variability (PEFV) was measured. A total of 23/41 patients corresponded to EP and 18/41 patients to NP. The PEFV was higher in EP than in NP. LTE4 was higher with NP than with EP. No difference was found for CC16. Montelukast reduced the predominant cell in both subsets, whereas budesonide only reduced eosinophils in EP. Budesonide and montelukast reduced PEFV in EP but not in NP. Considering the total treated-samples in each subset, CC16 level increased significantly in EP. In conclusion: a NP subset of asthmatic patients was identified. These patients show a lower bronchial lability; the leukotriene pathway is involved which responds to anti-leukotriene treatment. This phenotype shows a poor recovery of CC16 level after treatment.
El eosinófilo es considerado la célula protagonista principal en el asma; sin embargo, a menudo se observan discordancias entre las manifestaciones clínicas y la respuesta de los pacientes al tratamiento. Nos propusimos determinar la ocurrencia de predominio de neutrófilos en el asma e identificar las características clínico-funcionales, el patrón celular y las moléculas solubles del esputo inducido, para guiar el tratamiento apropiado anti-inflamatorio. Se incluyeron 41 pacientes: 21 a 40 años de edad, con asma estable leve a grave, no tratados con esteroides tópicos ni sistémicos y no fumadores. Se obtuvo una muestra de esputo inducido en condiciones basales, una segunda muestra después del tratamiento al azar con budesonida (400 µg dos veces al día) o el montelukast (10 mg/d) durante seis semanas, y una final después de un período de lavado de 4 semanas. En el frotis por citocentrifugado se evaluó el predominio de eosinófilos (EP) o neutrófilos (NP), y en el sobrenadante se determinó LTE4, y CC16. Se midió la variabilidad del flujo espiratorio máximo (PEFV). Un total de 23/41 pacientes correspondieron al EP y 18/41 pacientes con NP. El PEFV fue mayor en el EP que en NP. LTE4 fue mayor en NP que en EP. No se encontraron diferencias de los niveles de CC16 en ambos grupos. Montelukast redujo la célula predominante en ambos subgrupos, mientras que budesonida sólo redujo los eosinófilos en EP. Tanto budesonida como montelukast redujeron PEFV en EP, pero no en NP. El nivel de CC16 aumentó significativamente en el EP luego del tratamiento antiinflamatorio. En conclusión: se identificó un subgrupo de asmáticos NP que presentan una menor labilidad bronquial, la vía de los leucotrienos parece estar involucrada y responde al tratamiento anti-leucotrienos. Este fenotipo muestra una escasa recuperación del nivel de CC16 posterior al tratamiento.
Subject(s)
Adult , Female , Humans , Male , Young Adult , Anti-Asthmatic Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Asthma/drug therapy , Eosinophils/cytology , Neutrophils/cytology , Sputum/cytology , Acetates/therapeutic use , Asthma/pathology , Asthma/physiopathology , Budesonide/therapeutic use , Cell Count , Drug Therapy, Combination , Eosinophils/drug effects , Neutrophils/drug effects , Quinolines/therapeutic use , Severity of Illness Index , Single-Blind Method , Uteroglobin/physiologyABSTRACT
In the present study the in vivo and in vitro effects of GHRP-5 on the PRL-releasing activity in correlation with the morphological changes of lactotroph cells and their transcriptional activity were evaluated. The in vivo treatment (12 micrograms/100 g BW/day for 3 days) of male rats with GHRP-5 does not induce any significant changes in serum PRL levels. In contrast, the addition of GHRP-5 to pituitary cell cultures increased significantly the release of PRL. This effect is enhanced in cell cultures of enriched lactotrophs, increasing significantly the secretion of PRL, the concentrations of which were 50 higher than that of untreated control cells. The administration of GHRP-5 provokes several changes in the fine structure of lactotrophs, compatible with an increased secretory activity. After the GHRP-5 treatment the different lactotroph subtypes persist but the subtype I displaying secretory granules of larger size (500-900 nm) and a significant development of the Golgi apparatus and RER were more frequently observed. These results can be correlated with a significant augmentation in PRL mRNA after the GHRP-5 treatment. In spite of that no variations in serum PRL levels were observed in vivo, following GHRP-5 treatment, the lactotroph population experienced evident fine structure modifications, concordant with an upsurge of PRL synthesis. These observations confirmed a direct action of GHRP-5 on receptors expressed by lactotrophs. The differential actions of GHRP-5 on in vivo and in vitro designs confirm a different effectiveness of this secretagogue to induce PRL secretion.
Subject(s)
Animals , Male , Rats , In Vitro Techniques , Oligopeptides/pharmacology , Prolactin , Cells, Cultured , Pituitary Gland/cytology , Pituitary Gland/drug effects , Pituitary Gland , Prolactin , Rats, Wistar , RNA, MessengerABSTRACT
La Terapia Fotodinámica (PDT) es un tratamiento del cáncer basado en la acumulación específica de una droga fotosensible en el tejido maligno. Su posterior radiación con una longitud de onda apropiada, induce la producción de singuletes de oxígeno responsable de la peroxidación de las organelas y la muerte de las células neoplásicas. En el Centro de Microscopía Electrónica de la Universidad Nacional de Córdoba se diseñó y construyó un prototipo de fuente de irradiación no coherente de 630nm el que posibilitó la aplicación de PDT por primera vez en nuestro país. Este prototipo ha sido aplicado satisfactoriamente en el tratamiento de la queratosis actínica. Fueron tratadas 100 lesiones en 27 pacientes utilizando como fotosensibilizador al ácido d amino levulínico (ALA) al 20 por ciento La activación lumínica duró de 5 a 20 minutos dependiendo de la extensión y profundidad de la lesión. Los resultados obtenidos fueron los siguientes: Remisión Completa de las lesiones (RC) 84por ciento, Remisión parcial (RP) 10 por ciento, Sin respuesta (SR) 0 por ciento y Sin datos (SD) 6 por ciento. En el último grupo están incluidos aquellos pacientes que no retornaron para su evaluación. La alta efectividad, sumada a la inmejorable respuesta cosmética y la reducida agresividad, hacen de PDT el método de elección en el tratamiento de esta patología. El prototipo utilizado en este estudio demostró ser además de no invasivo y bien tolerado, altamente efectivo.
Subject(s)
Humans , Male , Female , Aged , Middle Aged , Levulinic Acids/therapeutic use , Precancerous Conditions/drug therapy , Keratosis/drug therapy , Photochemotherapy/instrumentation , Photosensitizing Agents/therapeutic use , Aged, 80 and over , Equipment Design , Remission InductionABSTRACT
The Leydig cells of the bat Tadarida brasiliensis, exhibit two well-defined periods of secretory activity that are intimately associated to the bat reproductive cycle. During the breeding season (August-September, late Winter and early Spring in the southern hemisphere), the interstitial tissue contains hypertrophic Leydig cells characterized ultrastructurally by the presence of pleomorphic mitochondria, depletion of lipid droplets, proliferation of membranes of agranular endoplasmic reticulum (AER) and enlargement of the Golgi complexes. By contrast, from Spring to Fall concurrent with regression of seminiferous tubules, the Leydig cells acquire a quiescent appearance with reduction in size and volume of AER membranes, atrophy of the Golgi complex and a massive storage of lipid droplets. The changes occurring in Leydig cells during the breeding season can be duplicated experimentally in non-breeding bats with exogenous stimulation with hCG. The gonadotropic treatment induces rapid changes in both interstitial cells and seminiferous tubules. The latter present evident signs of reactivation including proliferation of the spermatogenic cell line, permeation of the tubular lumen and depletion of lipid droplets. The Leydig cells display similar features to those found in the bat during the mating season at the peak of secretory activity. The bat T. brasiliensis is an excellent model to correlate the morphological organization of the Leydig cells with either seasonal fluctuations of its secretory activity or after experimental stimulation with gonadotropins.
Subject(s)
Animals , Male , Leydig Cells/physiology , Chiroptera/physiology , Leydig Cells/ultrastructure , Microscopy, Electron , Seasons , Testis/cytology , Testis/ultrastructureABSTRACT
The L-Triiodothyronine (L-T3) has a direct influence on the population of somatotrophs in rat pituitary gland. This effect is dose-dependent and induces both proliferation of somatotrophs and striking changes in the synthesis and secretion of grwth hormone (GH). Daily injections of 5 mug L-T3 for 7 days increased significantly the synthesis and storage of GH in pituitary gland, but the GH release was partially blocked. By contrast, injections of 10 mug L-T3 promote rapid synthesis and secretion of GH with removal of the cytoplasmic stores of the hormone and a consequent rise of serum levels. A close correlation was found between levels of stimulation and proliferation or retrogression of lactotroph cell population.