RESUMEN
AIM: To compare pulmonary deposition after inhalation with three different nebulisers in preterm infants under conditions relevant to practice. METHODS: The relative lung deposition (bioavailability) was estimated by inhalation of the marker substance, sodium cromoglycate (SCG), and measurement of urinary excretion of SCG. Seventeen spontaneously breathing preterm infants received 20 mg of SCG as nebuliser solution by means of (a) an LC Star jet nebuliser; (b) an LS 290 ultrasonic nebuliser; and (c) a Projet ultrasonic nebuliser in a randomised three-period, crossover design. Serial urine samples were collected until about 12 hours after inhalations, and the excreted SCG was determined by high-performance liquid chromatography. RESULTS: The mean (SD) total amounts of SCG excreted in urine measured after inhalation with the LC Star nebuliser (0.089 (0.036) mg) were significantly higher than those obtained with the LS 290 (0.055 (0.019) mg) or the Projet nebuliser (0.046 (0.025) mg). The average pulmonary deposition after inhalation using the LC Star, LS 290 and Projet devices was estimated as 0.89%, 0.55% and 0.46% of the nominal dose, respectively. CONCLUSION: Inhalation with the LC Star jet nebuliser producing the greatest proportion of droplets <2 mum yielded a higher lung deposition in preterm infants than the LS 290 and Projet ultrasonic nebulisers.
Asunto(s)
Antiasmáticos/farmacocinética , Cromolin Sódico/farmacocinética , Recien Nacido Prematuro/metabolismo , Pulmón/metabolismo , Administración por Inhalación , Antiasmáticos/administración & dosificación , Antiasmáticos/orina , Cromolin Sódico/administración & dosificación , Cromolin Sódico/orina , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro/orina , Masculino , Nebulizadores y VaporizadoresRESUMEN
The majority of elderly men is affected by benign and malignant diseases of the prostate. Both proliferative disorders, i.e., benign hyperplasia of the prostate (BPH) and prostate cancer (PCa)-which has recently emerged as the most common male malignancy in industrialized countries-seem to be governed by endocrine factors such as sex steroid hormones, but auto/paracrine factors are involved as well. Age-related changes in levels and ratios of endocrine factors as androgens, estrogens, gonadotropins, and prolactin (PRL) and changes in the balance between auto/paracrine growth-stimulatory and growth-inhibitory factors such as insulin-like growth factors (IGFs), epidermal growth factor (EGF), nerve growth factor (NGF), IGF-binding proteins (IGFBPs), and transforming growth factor beta (TGFbeta) are meant to be responsible for abnormal prostatic growth. We investigated the existence of putative local regulatory circuits involving the protein hormones, human growth hormone (hGH), human placental lactogen (hPL), and hPRL, and their corresponding receptors in prostatic tissue specimens (transurethral resections of the prostate, TURP; n = 11), in the prostatic cancer cell lines PC3, Du145, LnCap, a virus-transformed BPH cell line (BPH-1), and in a normal healthy prostate by RT-PCRs and highly specific and sensitive immunofluorometric assays (IFMA). Neither hPRL nor hGH was detected at the mRNA or protein levels in prostatic tissue and cell lines, with the exception of 2 of 11 prostatic TURP-samples, which showed weak expression of the PL-A/B genes. PRL- and GH-receptors were expressed in all normal and pathological prostatic specimens. Surprisingly, PRL-receptor expression was not detectable in prostatic cancer cell lines. The trophic effects of exogenous hGH, hPL, and hPRL were investigated by cell proliferation assays (WST-I) in prostatic primary cell cultures and PCa cell lines. hGH significantly (p < 0.005) increased cell proliferation up to 138+/-3.2% (1 nM hGH), while hPL and hPRL revealed only moderate effects. Our data suggest that local auto/paracrine networks of protein hormone actions are not involved in the pathology of BPH or prostatic cancer. On the other hand, systemic pituitary-derived hGH can increase the proliferative response of BPH and PCa, acting directly on the target organ prostate, via the hGH-R. In this case, envisaged GH substitution in elderly people must be viewed at with caution because age-related declines in GH/IGF-I could act as a protective mechanism against abnormal cell growth.
Asunto(s)
Envejecimiento/metabolismo , Envejecimiento/patología , Hormonas/metabolismo , Próstata/metabolismo , Próstata/patología , Receptores de Superficie Celular/metabolismo , Anciano , Anciano de 80 o más Años , Secuencia de Bases , División Celular/efectos de los fármacos , Cartilla de ADN/genética , Hormonas/genética , Hormonas/farmacología , Hormona de Crecimiento Humana/genética , Hormona de Crecimiento Humana/metabolismo , Hormona de Crecimiento Humana/farmacología , Humanos , Masculino , Persona de Mediana Edad , Lactógeno Placentario/genética , Lactógeno Placentario/metabolismo , Lactógeno Placentario/farmacología , Prolactina/genética , Prolactina/metabolismo , Prolactina/farmacología , Próstata/efectos de los fármacos , Hiperplasia Prostática/metabolismo , Neoplasias de la Próstata/metabolismo , Receptores de Superficie Celular/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales CultivadasRESUMEN
This report deals with the control of detrusor hyperreflexia by the intravesical instillation of oxybutynin hydrochloride (OH) in 10 male and 3 female patients with complete suprasacral spinal cord lesions having clean intermittent catheterisation (CIC) because of unbalanced voiding. The indication for intravesical OH application was persisting urinary incontinence despite CIC in 11 patients and in 2 patients detrusor hypercontractility. One 5 mg tablet of OH was dissolved in distilled water and the solution was instilled into the bladder through the catheter, which has been used for urodynamics and which was then removed. Six hours later cystometry was repeated and the clinical effects were studied especially with regard to continence/incontinence and side-effects. The differences in the cystometric bladder capacity and maximum detrusor pressure before and after instillation of OH are statistically highly significant. Clinically, from those 10 patients who were incontinent between CIC before, 9 remained dry during the 6-hour period. None of the patients reported any side-effect after intravesical application of OH. However, with subsequent oral medication 8 out of 12 patients complained of typical anticholinergic side-effects. These results indicate that treatment with topical OH is an effective alternative to treating detrusor hyperreflexia, especially in patients already on CIC because of unbalanced voiding, but with persisting urinary incontinence due to detrusor hyperreflexia. OH is well absorbed from the bladder, however absorption seems to be protracted compared to oral intake.