Síntomas de tramo urinario inferior y síndrome de apnea obstructiva del sueño: evolución urodinámica antes y después de un año de tratamiento con presión continua positiva de la vía aérea / Lower urinary tract symptoms and obstructive sleep apnea syndrome: Urodynamic evolution before and after one year of treatment with continuous positive airway pressure

Objetivo: Demostrar el potencial impacto urodinámico que puede tener el uso adecuado de presión continua positiva de la vía aérea (CPAP) en pacientes con síndrome de apnea-hipopnea obstructiva del sueño y observar si la posible mejoría de los síntomas de tramo urinario inferior es debida a alguna modificación urodinámica. Métodos: Estudio prospectivo con pacientes recientemente diagnosticados de síndrome de apnea-hipopnea obstructiva del sueño mediante poligrafía del sueño. Se estudian desde el punto de vista urológico para descartar importantes patologías urológicas. Se utilizan cuestionarios validados IPSS y OAB-V8, diarios miccionales de 3 días y estudios urodinámicos invasivos, todos ellos antes de comenzar con CPAP y tras un año de su uso adecuado. Resultados: Se llevan a cabo 84 estudios urodinámicos en 43 pacientes. La puntuación IPSS disminuye 3,58 puntos. La puntuación OAB-V8 disminuye 2,87 puntos. Los episodios de nicturia disminuyen más de uno por noche. El porcentaje de pacientes con poliuria nocturna disminuye un 26%. La acomodación vesical significativamente aumenta (97,39 vs. 200,40 ml/cm H2O). Disminuye la presencia de detrusor hiperactivo en el estudio urodinámico de 11 (antes de CPAP) a 5 pacientes (tras CPAP). Conclusión: Tras el tratamiento apropiado con CPAP se observa una mejoría estadística y clínica de distintos síntomas de tramo urinario inferior con escasa repercusión urodinámica

Objective: To report the clinical evolution and the urodynamic behaviour of several lower tract urinary symptoms in patients with obstructive sleep apnea syndrome before and after the treatment with continuous positive airway pressure (CPAP) devices. Methods: A prospective study was performed; patients with recent diagnosis of sleep apnea confirmed by nocturnal sleep polygraphy and absence of medical urological past history. In order to discard important lower urinary tract conditions, urological examinations were previously performed. Urinary symptoms were evaluated using the IPSS and OAB-V8 validated questionnaires, three-day Bladder Diary and invasive urodynamic examinations with a gap of one year before and one year after using the CPAP. Results: 84 urodynamic studies were carried out in 43 patients. The IPSS score decreased by 3.58 points. The OAB-V8 score decreased by 2.87 points. Nocturia episodes decreased to one per night. The percentage of patients with nocturnal polyuria went down to 26%. The bladder compliance significantly increased (97.39 vs 200.40ml/cm H2O). The presence of detrusor overactivity decreased from 11 (before CPAP) to 5 patients (after CPAP). Conclusion: The proper treatment with CPAP showed a statistical and clinical improvement of several LUTS with limited urodynamic modifications

Lower urinary tract symptoms and obstructive sleep apnea syndrome: Urodynamic evolution before and after one year of treatment with continuous positive airway pressure. / Síntomas de tramo urinario inferior y síndrome de apnea obstructiva del sueño: evolución urodinámica antes y después de un año de tratamiento con presión continua positiva de la vía aérea.

OBJECTIVE: To report the clinical evolution and the urodynamic behaviour of several lower tract urinary symptoms in patients with obstructive sleep apnea syndrome before and after the treatment with continuous positive airway pressure (CPAP) devices. METHODS: A prospective study was performed; patients with recent diagnosis of sleep apnea confirmed by nocturnal sleep polygraphy and absence of medical urological past history. In order to discard important lower urinary tract conditions, urological examinations were previously performed. Urinary symptoms were evaluated using the IPSS and OAB-V8 validated questionnaires, three-day Bladder Diary and invasive urodynamic examinations with a gap of one year before and one year after using the CPAP. RESULTS: 84 urodynamic studies were carried out in 43 patients. The IPSS score decreased by 3.58 points. The OAB-V8 score decreased by 2.87 points. Nocturia episodes decreased to one per night. The percentage of patients with nocturnal polyuria went down to 26%. The bladder compliance significantly increased (97.39 vs 200.40ml/cm H2O). The presence of detrusor overactivity decreased from 11 (before CPAP) to 5 patients (after CPAP). CONCLUSION: The proper treatment with CPAP showed a statistical and clinical improvement of several LUTS with limited urodynamic modifications.

Estudio preliminar de los tratamientos de infecciones del tracto urinario registrados en oficinas de farmacia como base para un estudio del impacto de la atención farmacéutica en estos pacientes / Preliminary study of the treatments of urinary tract infections recorded in community pharmacies as the basis for a study of the impact of pharmaceutical care in these patients

Objetivos: Conocer el perfil de los pacientes que acuden a las farmacias para iniciar un tratamiento de la infección del tracto urinario, el tipo de medicamentos prescrito y la presencia de recurrencia en cada paciente. Método: Estudio prospectivo de recogida de datos de las dispensaciones efectuadas en 7 farmacias de Asturias durante 4 meses y siguiendo el procedimiento descrito en FORO 2008. El dato de recurrencia se obtuvo mediante preguntas adicionales a la entrevista-tipo usada en el estudio. Resultados: Se estudiaron 110 casos, de 20 hombres (18,2%) y 90 mujeres (81,8%). La media de edad en los hombres fue de 62,6 años (rango: 23-85) y en las mujeres de 58,7 (rango: 18-94). El 59% de las mujeres tenía más de 50 años y había 4 embarazadas (4,5%). En las mujeres, el 43% de las prescripciónes fueron quinolonas (33% norfloxacino y 10% ciprofloxacino), el 41% fosfocina y el 12% betalactámicos. En los hombres, el 75% de las prescripciones fueron quinolonas (50% ciprofloxacino y 25% norfloxacino), el 15% fosfocina y el 5% amoxicilina-clavulánico. Las pautas fueron homogéneas para cada tipo. De los 110 pacientes entrevistados, el 50% recordaba haber tenido una infección urinaria en los últimos 6 meses o más de una en el último año. No se obtuvo este dato en el 13% de los casos. Conclusiones: El perfil demográfico de los pacientes coincide con el de otros estudios publicados. El patrón de prescripción es muy homogéneo en cuanto a la selección de los principios activos, acorde con la bibliografía publicada desde 2003. Las pautas de prescripción parecen estar más influidas por las presentaciones disponibles en el mercado que por las guías clínicas. La presencia de recurrencias parece elevada, aunque no hay datos cuantitativos disponibles de este problema en nuestro entorno (AU)

Objectives: To collect the demographic data of patients who come to pharmacies to initiate drug treatment for a urinary tract infection (UTI), to and determine the classes of drugs prescribed and the incidence of recurrence in each patient. Method: A prospective study involving the collection of data on the drugs prescribed for UTI dispensed at seven pharmacies in Asturias over a four-month period, following the procedure for drug dispensing described in the FORO 2008 document. The data on recurrence was obtained by including additional questions in the interview employed in the study. Results: We studied 110 cases: 20 men (18.2%) with a mean age of 62.6 years (range: 23-85 years) and 90 women (81.8%) with a mean age of 58.7 (range: 18-94 years); 59% of the women were over 50 years of age. Four of the women were pregnant (4.5%). The kinds of drugs prescribed to women (n=90) were: quinolones (43% [norfloxacin in 33% and ciprofloxacin in 10%]); fosfomycin in 41% and beta-lactams in 12%. For men (n=20) they were: quinolones (75% [ciprofloxacin in 50% and norfloxacin in 25%]); fosfomycin in 15% and betalactams in 5%. Dosing was very similar for each class. Of the 110 patients interviewed, 50% recalled having had another UTI within the preceding six months or at least two over the previous year. Data concerning recurrence was not obtained in 13% of the cases. Conclusions: The demographic profile of the patients is similar to that described in other primary care studies on UTI in the literature. The types of drugs prescribed do not vary widely, following recent indications of clinical guidelines for Primary Care since 2003; not so the dosing, which seems to be more influenced by the presentations available in the pharmaceutical market than by the clinical guidelines. The rate of recurrence seems high, but we have no quantitative reference data on this problem in our region (AU)

Preliminary study of the vasorelaxant effects of (+)-nantenine, an alkaloid isolated from Platycapnos spicata, in rat aorta.

In this work, the potential vasorelaxant activity of (+)-nantenine, an alkaloid isolated from Platycapnos spicata, was studied for the first time in rat aorta. (+)-Nantenine (3 - 30 microM) totally relaxed, in a concentration-dependent manner and with almost equal effectiveness, the contractions induced by noradrenaline (NA) or by a high KCl concentration (60 mM) in intact rat aortic rings. Mechanical removal of endothelium and/or pretreatment of aorta rings with glibenclamide (10 microM) or tetraethylammonium (TEA, 2 mM) did not significantly modify the vasorelaxant effects of this aporphine alkaloid. In the experiments in Ca(2+)-free medium, (+)-nantenine (10 microM) had no effect on caffeine-induced contractions. Furthermore, in the studies with radiolabelled Ca(2+), (+)-nantenine (3 - 30 microM) did not modify the basal uptake of (45)Ca(2+) but decreased, in a concentration-dependent fashion, the influx of (45)Ca(2+) induced by NA and KCl in endothelium-containing and endothelium-denuded rat aortic rings. In addition, (+)-nantenine (3 - 30 microM) was ineffective to scavenge superoxide anion (O(2) (-)) radicals generated by the hypoxanthine (HX)-xanthine oxidase (XO) system and/or to inhibit XO activity. These results indicate that: a) the vasorelaxant effects of (+)-nantenine in rat aorta are due, at least in part, to a blockage of Ca(2+) influx through transmembrane calcium channels, b) the activation of ATP-sensitive K(+) channels (K(ATP)) and large conductance Ca(2+)-activated K(+) channels (K(Ca)) present in smooth muscle cells, the presence (integrity) of endothelial system, an inhibitory action on XO enzymatic activity and/or O(2)(-) radicals scavenging properties are not involved in the vascular effects of (+)-nantenine in rat aorta described above.

Study of the in vivo and in vitro cardiovascular effects of (+)-glaucine and N-carbethoxysecoglaucine in rats.

1. The cardiovascular and vasorelaxant effects of (+)-glaucine and of a semisynthetic derivative (N-carbethoxysecoglaucine) were studied in rats. 2. N-carbethoxysecoglaucine did not modify either systolic arterial pressure or heart rate values in conscious (25 mg kg-1, p.o.) and anaesthetized normotensive rats (5 mg kg-1, i.v.). Furthermore, this compound showed no activity in the experiments carried out on rat isolated aorta [contractility and 45Ca2+ influx assays (5 microM)] and did not modify the rate and force of contraction in rat isolated atria (5 microM). 3. In conscious normotensive rats, oral administration of (+)-glaucine (25 mg kg-1) did not modify either systolic arterial pressure or heart rate. 4. In anaesthetized normotensive rats, (+)-glaucine (5 mg kg-1, i.v.) produced a remarkable fall in mean arterial pressure (MAP) accompanied by a significant decrease in heart rate. In the same preparation, (+)-glaucine (5 mg kg-1, i.v.) did not modify the cardiovascular effects induced by noradrenaline (NA) (5 micrograms kg-1) and 5-hydroxytryptamine (5-HT) (300 micrograms kg-1) but markedly inhibited those induced by nicotine (200 micrograms kg-1). 5. In isolated intact aorta of rat, (+)-glaucine (0.15-5 microM) competitively inhibited the contractions induced by NA (with a pA2 value of 7.14) and non-competitively those induced by 5-HT (in normal Krebs solution) and Ca2+ (in depolarizing Ca(2+)-free high-K+ 50 mM solution), with depression of the maximal response and with pD2 values of 5.56 and 5.26, respectively. 6. In experiments in Ca2+-free medium, (+)-glaucine (3 microM) inhibited the contractions induced by NA and had no effect on either 5-HT- or caffeine-induced contractions.7. Furthermore, in the experiments with radioactive Ca2+, (+)-glaucine (3 microM) did not modify the basal uptake of 45Ca2+ but strongly inhibited the influx of 45Ca2+ induced by NA, 5-HT and K+.8. (+)-Glaucine (5microM) had no effect on rate and force of contraction in rat isolated atria.9. These results indicate that: (a) the cardiovascular effects (hypotension and bradycardia) of (+)-glaucine in anaesthetized normotensive rats (5 mg kg-1) may be due, at least in part, to a ganglioplexic effect; (b) the vasorelaxant action of ( + )-glaucine (0.15-5 microM) in rat isolated aorta can be attributed to an alpha1-adrenoceptor blocking property (which may explain its inhibition of noradrenaline-induced 45Ca2+influx and contractions in normal Krebs solution and noradrenaline-induced contractions in Ca2+-free medium) and to a Ca2+-antagonist activity (which may be responsible, at least in part, for the inhibition of 45Ca2+ uptake induced by NA, 5-HT and K+ and the contractions induced by both NA and 5-HT in normal Krebs solution and by Ca2+ in Ca2+-free high-K+ medium) and (c) there is no correlation between the mechanisms of action observed for (+ )-glaucine in vivo and in vitro, which suggests that the vasorelaxant activity of this alkaloid does not contribute to its hypotensive activity.

Pharmacological study of several effects of hydralazine in the bisected rat vas deferens.

We have studied several effects of hydralazine in the bisected rat vas deferens. Hydralazine produced a shift to the left of the concentration-response curve for noradrenaline, with potentiation of the maximal response in both portions of the vas deferens. In contrast it caused a shift to the right of the concentration-response curve for noradrenaline in preparations pretreated with cocaine (inhibitor of catecholamine neuronal uptake), and of the curve for methoxamine and for CaCl2 (in depolarizing medium with K+ 55 mM), in all cases with depression of the maximal response. Hydralazine enhanced the contractions induced by noradrenaline in Ca(2+)-free medium, except in the presence of cocaine. It had no effect on [3H]noradrenaline neuronal uptake into noradrenergic neurons of the vas deferens, nor did it affect basal or K(+)-induced 45Ca2+ uptake. These results suggest that hydralazine potentiates the contractions elicited by noradrenaline by a mechanism other than blockade of the neuronal uptake of this catecholamine. Our results also suggest that the inhibition by hydralazine of the contractions elicited by Ca2+ (in Ca(2+)-free depolarizing high-K+ 55 mM solution) and by methoxamine is not due to an action on voltage-dependent Ca2+ channels, but may reflect an intracellular site of action.

Effects of hydralazine on contractile responses to alpha 1 and alpha 2-adrenoceptor agonists in isolated rubbed rat aorta.

1. Effects of hydralazine on contractile responses to noradrenaline (an alpha 1- and alpha 2-adrenoceptor agonist) to phenylephrine and methoxamine (both selective alpha 1-adrenoceptor agonists) and to clonidine and BHT-920 (both relatively selective alpha 2-adrenoceptor agonists) were examined in isolated rat aorta deprived of endothelium. Hydralazine (1 mM) produced a rightward shift with depression of the maximal tension of the concentration-response curves for all the agonists tested. The effects on curves for clonidine and BHT-920 (partial agonists) were greater than on curves for noradrenaline, phenylephrine and methoxamine (full agonists). 2. The inhibitory effect of prazosin (pA2, about 10) was much greater than that of yohimbine (pA2, about 7) for all the agonists. 3. In tissues pretreated with phenoxybenzamine, hydralazine (1 mM) inhibited the residual response to all the agonists. The inhibitory effect on residual response to full agonists was similar to that observed on response to partial agonists in tissues not treated with phenoxybenzamine. 4. The relationship between maximal response and percentage receptor occupancy was nonlinear for full agonists, but near-linear for partial agonists. 5. These results indicate that the responses induced by noradrenaline, phenylephrine, methoxamine, clonidine and BHT-920 in the rat aorta are due to the activation of alpha 1-adrenoceptors and confirm the vasorelaxant action of hydralazine. 6. These results also suggest that the differential effects of hydralazine on the responses to alpha-adrenoceptor agonists may be due to differences in the amount of receptor reserve available available in this blood vessel for full agonists (noradrenaline, phenylephrine or methoxamine) and partial agonists (clonidine or BHT-920).

Study of the mechanism of the relaxant action of (+)-glaucine in rat vas deferens.

1. Effects of the aporphinoid alkaloid, (+)-glaucine, on rat vas deferens were investigated. 2. (+)-Glaucine (2-18 microM) competitively inhibited contractions induced by noradrenaline and methoxamine with a pA2 value of about 6. 3. (+)-Glaucine (2 and 18 microM) did not change the accumulation of tritium during incubation of the vas deferens with [3H]-noradrenaline. 4. (+)-Glaucine (0.3 nM-0.1 mM) inhibited specific [3H]-prazosin binding to membranes from rat vas deferens with a pKi value of 6.63, which is close to the pA2 value obtained against noradrenaline and methoxamine in functional studies. 5. In electrically-stimulated rat vas deferens, (+)-glaucine (0.3-10 microM) enhanced twitch contractions and competitively antagonized the inhibitory effect of clonidine with a pA2 value of 5.91. 6. In tissues incubated in depolarizing calcium-free high-potassium medium, (+)-glaucine (30-80 microM) inhibited Ca(2+)-induced contractions with depression of the maximal response at higher doses and with a pD'2 value of 3.65. Furthermore, (+)-glaucine (50 microM) did not modify basal 45Ca uptake but strongly inhibited the influx of 45Ca induced by K+. 7. These results suggest that (+)-glaucine has non-selective alpha 1- and alpha 2-adrenoceptor blocking properties. At higher doses, (+)-glaucine shows calcium antagonist activity which may be responsible, at least in part, for the inhibition of the contractions induced by Ca2+ in calcium-free high-potassium medium.

Effects of platelet activating factor on contractions and 45Ca influx induced by noradrenaline and potassium in rat rubbed and intact aorta. Comparison with its hypotensive effect in anaesthetized normotensive rats.

In order to clarify the mechanism of hypotensive activity of platelet activating factor (PAF), the effects of this drug on blood pressure in anaesthetized normotensive rats, on KCl- and noradrenaline-induced 45Ca uptake and contractile responses in rat aorta rings with and without endothelium were studied. PAF (3 micrograms kg-1, i.v.) showed long-lasting hypotensive effects in anaesthetized normotensive rats accompanied by a significant increase in heart rate. PAF (0.1-10 microM) did not relax the contractions induced by noradrenaline (10 microM) or K+ (60 mM) in rubbed or intact rat aorta. PAF did not affect the basal uptake of 45Ca2+ nor that induced by the two vasoconstrictor agents. In experiments in a calcium free medium, PAF (10 microM) had no effect on the noradrenaline- (10 microM) induced contractions. These results suggest that the hypotensive activity of PAF in normotensive anaesthetized rats is not due to a direct effect on rubbed and intact rat aorta rings (acting within the cell or blocking Ca2+ influx through L-type transmembrane calcium channels).