Evaluation and treatment of sleep disorders in adolescents.

Sleep disorders are quite common in adolescents and sleep disturbances occur most often during the mid-adolescent years. These disorders result in considerable negative consequences in terms of increased accidents, decreased academic performance, and increased behavioral difficulties. Over the past 25 years, the evaluation, diagnosis, and treatment of sleep-related breathing disorders has undergone dramatic changes. The diagnosis and treatment of pediatric sleep disorders are now the focus of more complex and collaborative research efforts. This article discusses the differences between childhood and adolescent sleep cycles, delayed sleep phase syndrome, sleep-related breathing disorders, narcolepsy, parasomnias, and behavior-related sleep problems.

cGMP inhibition of endothelin-stimulated inositol phosphate production in the fetal lamb pulmonary artery.

Endothelin-1 (ET-1) stimulates inositol phosphate production in vascular smooth muscle. In the present study, interactions between cyclic GMP (cGMP), cyclic AMP (cAMP) and ET-1 in fetal lamb pulmonary arteries were investigated using phosphoinositide hydrolysis studies and tissue bath techniques. ET-1 was found to be a potent vasoconstrictor of these vessels, with an EC50 of 15.8 nM. ET-1 stimulated total inositol phosphate (IP) production; basal IP production was 68 cpm/mg vs. 247 cm/mg with 1 microM ET-1. 8-bromo-cGMP (2 mM) significantly increased the threshold of ET-1 concentration for pulmonary artery contraction, but had no effect on IP production. Zaprinast (a selective type V phosphodiesterase inhibitor, 60 microM) did not affect ET-1-induced contractility or IP production. IBMX (0.5 mM), a non-specific phosphodiesterase inhibitor, inhibited the potent and maximal effects of ET-1 in arterial contraction and decreased ET-1-stimulated IP production by 49%, while forskolin had a lesser effect in the tissue bath and no effect on IP production. Thus, 8-bromo-cGMP and IBMX alter the contractile effects of ET-1 in the fetal pulmonary artery and IBMX also inhibits inositol phosphate production. The cross-talk mechanisms of these agents require further investigation.

The respiratory system in connective tissue diseases.

Adolescents with connective tissue diseases (CTDs) are at risk for community-acquired and opportunistic respiratory tract infections; it is mandatory to consider an infectious etiology in the differential diagnosis. The authors highlight the respiratory manifestations of the more common CTDs seen in adolescence, and also discuss useful diagnostic tests and drug regimens.

Heterogeneity of tachykinin receptors in the rabbit lung.

The tachykinins, substance P (SP) and neurokinin A (NKA), are agonists for the NK(1) and NK(2) receptors, respectively. Tachykinins have various respiratory effects, including bronchoconstriction. This study characterizes tachykinin binding sites in the rabbit lung. We hypothesize that (2-[(125)I]iodohistidyl(1))Neurokinin A ([(125)I]NKA) interacts with NK1 and NK2 binding sites in the rabbit lung. The K d determined from saturation isotherms was 0.69 times/divided by 1.14 nM (geometric mean times/divided by SEM) and the B max was 4.15 + or - 0.22 femtomole/mg protein (arithmetic mean + or - SEM). Competitive inhibition studies with NKA, SP and various selective tachykinin agonists showed the rank order of potency; [beta-Ala(8)]-Neurokinin A 4-10 = SP >> NKA >> [Sar(9),Met(02)11]-Substance P. [beta-Ala(8)]-Neurokinin A 4-10, a selective NK(2) agonist, and SP inhibition of [(125)I]NKA binding were best described using a two-site model. Competitive inhibition studies using the selective nonpeptide NK(2) antagonist (SR 48968) and the selective nonpeptide NK(1) antagonist (CP 96,345) revealed Ki's of 5.5 nM and 8.1 nM, respectively. Our data therefore suggest that [(125)I]NKA binds to both the NK(1) and NK(2) receptors in the lung.

Persistent pulmonary hypertension of the newborn. Role of nitric oxide and endothelin in pathophysiology and treatment.

Persistent pulmonary hypertension of the newborn (PPHN) results in significant morbidity and mortality in otherwise normal term infants. Safe, effective therapies for PPHN will only be possible when they can be directed toward the specific defects producing this condition. In this review, the authors discuss three different categories of mediators that may play a role in the normal transition at birth and in the pathophysiology seen in PPHN: (1) lipid mediators, (2) the peptide endothelin, and (3) the oxidant radical, nitric oxide. The potential of using the last mediator, nitric oxide, as a treatment for PPHN is under intensive investigation and is discussed in the final section.