Association of halo nevus/i and vitiligo in childhood: a retrospective observational study.

BACKGROUND: Although halo nevus (HN) is frequently observed, the relationship between vitiligo and HN in children has rarely been investigated. OBJECTIVES: To investigate the association between HN and vitiligo in children and understand if HN/HNi might be a risk factor for vitiligo. METHODS: Ninety-eight patients with only HN/HNi and 27 with HN/HNi and vitiligo were investigated for number and localization of HN/HNi, family history for HN/HNi and vitiligo and personal and family history for autoimmune or other diseases. A follow-up telephone interview was performed to investigate the evolution of HN/HNi and the possible onset of vitiligo and/or other diseases. RESULTS: In the HN/HNi and vitiligo group, HN/HNi and vitiligo had started almost simultaneously in 11 children; in nine, the onset of HN/HNi was followed by vitiligo after 6 months to 5 years; seven patients presented vitiligo first and HN/HNi after 3-9 years. Patients with associated vitiligo had, significantly more often, multiple HNi and a positive personal and/or family history of autoimmune thyroiditis compared with those with only HN/HNi. Follow-up longer than 5 years was available in 54/98 patients with only HN/HNi; two of them, both with multiple HNi, developed vitiligo. After follow-up, multiple HNi were noticed in 18/52 patients without vitiligo and in 9/11 of those in whom HN/HNi heralded vitiligo (s.s.). CONCLUSIONS: In patients with multiple HNi, the risk of vitiligo and other autoimmune diseases seems to be higher than in pediatric patients with a single HN; clinicians should pay particular attention to children with multiple HNi and personal or family history of autoimmune diseases.

Developmental effects of in vivo and in vitro inhibition of nitric oxide synthase in neurons.

The diffusible chemical messenger nitric oxide (NO) is involved in neuronal plasticity and it is, therefore, supposed to play a role in brain development. A shortage of NO during the critical period of brain maturation may theoretically have long-lasting consequences on the organization of the adult brain. We have performed in neonatal rats a chronic inhibition of the enzyme responsible for NO production, nitric oxide synthase (NOS), from postnatal day 3 to postnatal day 23, through administration of the competitive antagonist N-nitro-L-arginine methylester (L-NAME). The calcium-dependent catalytic activity resulted almost completely inhibited throughout the period of treatment and it took more than 4 days after its suspension to get a full recovery. The expression of the neuronal isoform of the enzyme (nNOS), revealed by immunoblotting, was unchanged during the treatment and after it. The histochemical reaction for NADPH diaphorase was reduced at the end of the treatment and recovered in concomitance with the recovery of the catalytic NOS activity. No gross structural alterations were detected in brain morphology. The levels of three neurotransmitter-related and one astrocytic marker were unchanged in the cerebellum, hippocampus and cortex of 60-day-old rats which had been neonatally treated. A similar lack of significant effects on neurochemical brain maturation was also noticed in a parallel series of experiments, in which a short pulse of NOS inhibition was performed at a critical prenatal time of brain development, from gestational day 14 to gestational day 19. In vitro, chronic exposure of cerebellar granule cells to L-NAME (500 microM) resulted in slight decrease of surviving neurons after 8 days in culture and in better resistance to the challenge of stressful culture conditions. The present results suggest that the basic plan of brain organization can be achieved despite an almost complete NOS inhibition during the maturation period. In vitro, NOS inhibition may bring to more pronounced consequences on neuronal viability and function.

Ornithine decarboxylase activity during development of cerebellar granule neurons.

Ornithine decarboxylase (ODC), the key enzyme for polyamine biosynthesis, dramatically decreases in activity during normal cerebellar development, in parallel with the progressive differentiation of granule neurons. We have studied whether a similar pattern is displayed by cerebellar granule neurons during survival and differentiation in culture. We report that when granule cells were kept in vitro under trophic conditions (high K+ concentration), ODC activity progressively decreased in parallel with neuronal differentiation. Under nontrophic conditions (cultures kept in low K+ concentration), the enzymatic activity dropped quickly in parallel with an increased apoptotic elimination of cells. Cultures kept in high K+ but chronically exposed to 10 mM lithium showed both an increased rate of apoptotic cell death at 2 and 4 days in vitro and a quicker drop of ODC activity and immunocytochemical staining. A short chronic treatment of rat pups with lithium also resulted in transient decrease of cerebellar ODC activity and increased programmed cell death, as revealed by in situ detection of apoptotic granule neurons. The present data indicate that a sustained ODC activity is associated with the phase of survival and differentiation of granule neurons and that, conversely, conditions that favor their apoptotic elimination are accompanied by a down-regulation of the enzymatic activity.