Use of biologic agents in pediatric psoriasis.

Psoriasis affects approximately 2 percent of the population. Approximately 30-45 percent of those affected first experience symptoms during childhood or adolescence. Although biologics have proven to be a relatively safe and effective treatment option for adults with psoriasis, limited information is available regarding the use of biologic agents in pediatric patients with psoriasis. The authors attempt to assess and summarize the available data on the use of biologic agents in patients under the age of 18, regardless of the indication, as well as to examine the limited available data on the use of biologics for psoriasis in the pediatric population. In doing so, the authors aim to provide guidance on the safety and efficacy of biologic therapies in pediatric patients with psoriasis. The authors' findings suggest that biologic agents should be considered for use solely in children with psoriasis that is refractory to conventional therapies, including children currently with severe, widespread, refractory pustular, plaque or psoriatic arthritis. Of all the currently available biologics, etanercept appears to have resulted in fewer and less severe side effects compared to infliximab in the juvenile rheumatoid arthritis population. In addition, while biologics are generally safe and effective in the pediatric population, serious adverse events (including infection), have been reported in the literature and should be taken into account before beginning treatment with any biologic agent. The physician and parents of the patient must carefully consider the risk-benefit ratio when deciding whether to use these medications. Additional randomized, controlled trials are needed to adequately assess the safety and efficacy of biologic medications for childhood psoriasis.

Androgen-mediated induction of the kidney arachidonate hydroxylases is associated with the development of hypertension.

Hypertension is a leading cause of cardiovascular, cerebral, and renal disease morbidity and mortality, and epidemiological evidence suggests a role for sex-dependent mechanisms in the pathophysiology of hypertension. We show here that treatment of rats with 5alpha-dihydrotestosterone increases the activity of the kidney arachidonate omega/omega-1 hydroxylase and the biosynthesis of 20-HETE (165 and 177% of control untreated male and female rats, respectively) and raises the systolic blood pressures of male and females rats by 46 and 57 mmHg, respectively. These androgen effects are associated with an upregulation in the kidney levels of CYP 4A8 mRNA and a decrease in CYP 4A1 transcripts. Dissected renal microvessels, the target tissue for most of the prohypertensive actions of 20-HETE, show an androgen-dependent upregulation of vascular CYP 4A8 mRNA and a fourfold increase in 20-HETE synthase activity. We propose that androgens regulate renal function and systemic blood pressure through a combination of transcriptional and hemodynamic mechanisms that are ultimately responsible for the regulation of renovascular tone and function.

Cytochrome P-450 4A isoform expression and 20-HETE synthesis in renal preglomerular arteries.

20-Hydroxyeicosatetraenoic acid (20-HETE), a potent vasoconstrictor and mediator of the myogenic response, is a major arachidonic acid metabolite in the microvasculature of the rat kidney formed primarily by the cytochrome P-450 (CYP) 4A isoforms, CYP4A1, CYP4A2, and CYP4A3. We examined CYP4A isoform expression and 20-HETE synthesis in microdissected interlobar, arcuate, and interlobular arteries; mRNA for all CYP4A isoforms was identified by RT-PCR. Western blot analysis indicated that the levels of CYP4A2/4A3-immunoreactive protein increased with decreased arterial diameter, whereas those of CYP4A1-immunoreactive protein remained unchanged. 20-HETE synthesis was the highest in the interlobular arteries (17 +/- 1.62 nmol. mg(-1). h(-1)) and, like CYP4A2/4A3-immunoreactive protein, decreased with increasing vessel diameter (4.5 +/- 1.21, 2.65 +/- 0.58, and 0.81 +/- 0.14 nmol. mg(-1). h(-1) in the arcuate, interlobar, and segmental arteries, respectively). 20-HETE synthesis in the renal artery and the abdominal aorta was undetectable. The observed decreased immunoreactivity of NADPH-cytochrome P-450 (c) oxidoreductase with increased arterial diameter provided a possible explanation for the decreased capacity to generate 20-HETE in the large arteries. The increase in CYP4A isoform expression and 20-HETE synthesis with decreasing diameter along the preglomerular arteries and the potent biological activity of 20-HETE underscore the significance of 20-HETE as a modulator of renal hemodynamics.