Diminished aromatase immunoreactivity in the hypothalamus, but not in the basal forebrain nuclei in Alzheimer's disease

In previous studies we have shown in Alzheimer's disease (AD) an enhanced nuclear estrogen receptor (ER) alpha expression in the cholinergic basal forebrain nuclei, i.e. the vertical limb of the diagonal band of Broca (VDB) and the nucleus basalis of Meynert (NBM), and in a number of hypothalamic nuclei, i.e. the supraoptic nucleus (SON), the infundibular nucleus (INF), the medial mamillary nucleus (MMN). We aimed at determining whether the increase in nuclear ERalpha seen in AD patients was related to a rise in local production of estrogens by aromatase (P-450arom), which is a key enzyme that catalyzes the biosynthesis of estrogens from precursor aromatizable androgens. We confirmed for the first time the presence of aromatase mRNA in neurons and glial cells in the human NBM and the tuberomamillary nucleus by RT-QPCR using laser microdissection. Enhanced aromatase immunoreactivity (ir) was indeed observed in the NBM in AD. However, in contrast a decreased aromatase-ir was found in the SON, INF and MMN of AD patients. In addition, P-450arom-ir was clearly diminished in ependymal and choroid plexus cells in AD. While an increase in aromatase-ir was found in the NBM and SON during normal aging, a decrease in staining was observed in the MMN. No sex differences in young control, elderly control or AD patients were present in any of the nuclei studied. In conclusion, brain P-450arom-ir and the relationship of its regulation with plasma sex steroid levels, estrogen and androgen receptors in the human hypothalamus and basal forebrain are region-specific.     

A clinical study comparing methyl aminolevulinate photodynamic therapy and surgery in small superficial basal cell carcinoma (8–20 mm), with a 12‐month follow‐up.

Objective To compare the efficacy and cosmetic outcome (CO) of photodynamic therapy with topical methyl aminolevulinate (MAL‐PDT) with simple excision surgery for superficial basal cell carcinoma (sBCC) over a 1‐year period. Methods In this multicentre, randomised, controlled, open study, patients were treated at baseline either with MAL‐PDT (two sessions, 7 days apart, repeated 3 months later if incomplete clinical response) or surgery (at baseline). Primary endpoints were clinical lesion response (CR) 3 months after last treatment and CO assessed by the investigator 12 months after last treatment. Secondary endpoints were CR at 12 months (i.e. recurrence) and CO assessed by the investigator at 3 and 6 months and by the patient at 3, 6 and 12 months. Results Overall, 196 patients were enrolled with 1.4 sBCC lesions on average per patient. Mean lesion count reduction at 3 months was 92.2% with MAL‐PDT vs. 99.2% with surgery [per protocol (PP) population] confirming the non‐inferiority hypothesis (95% confidence interval, –12.1, –1.9). A total of 92.2% lesions showed CR at 3 months with MAL‐PDT vs. 99.2% with surgery (PP population). At 12 months, 9.3% lesions recurred with MAL‐PDT and none with surgery. CO was statistically superior for MAL‐PDT at all time points. At 12 months, 94.1% lesions treated with MAL‐PDT had an excellent or good CO according to the investigator compared with 59.8% with surgery. This difference was confirmed with the patients’ assessment. The proportion of excellent CO markedly improved with time with MAL‐PDT unlike surgery. Conclusions MAL‐PDT offers a similarly high efficacy and a much better CO than simple excision surgery in the treatment of sBCC.