[Selective vitamin D receptor activation: effect on renal physiopathology]. / L'attivazione selettiva dei VDR: impatto sulla fisiopatologia renale.

The wide distribution of the vitamin D receptor (VDR) suggests that its activators (VDRAs) are involved in diverse organ functions including the cardiovascular, immune, and reproductive systems. These actions are likely to be independent of PTH and calcium/phosphorus levels. Earlier studies had shown that calcitriol was able to favorably influence experimental nephritis, remnant kidney glomerulosclerosis, and interstitial fibrosis, mediated through inhibition of inflammatory cytokines. Recently, VDRAs were shown to inhibit the reninangiotensin system (RAS), acting directly on the renin gene promoter. This action is independent of the systemic RAS blockade. VDRAs also inhibit other important gene promoters including NF-kB and p65, which are known to foster inflammation and fibrogenesis. These multiple actions result in a decrease in macrophage infiltration, fibroblast activation, and endothelial mesenchymal transition in the kidney. These findings represent the rationale for the use of VDRAs, in association with RAS blocking agents, to counteract the progression of renal injury characterized by inflammation and neofibrogenesis. However, despite promising preliminary results, the human studies available to date do not allow to draw definitive conclusions on this matter.

Peripheral benzodiazepine receptors on platelets of fibromyalgic patients.

OBJECTIVE: The aim of the present study was to analyze if alterations of peripheral-type benzodiazepine receptor (PBR) characteristics occurred in platelet membranes of patients affected by primary fibromyalgia (FM). DESIGN AND METHODS: Platelets were obtained from 30 patients with FM. Evaluation of kinetic parameters of PBR was performed using [(3)H] PK11195 as specific radioligand compared with 16 healthy volunteers. RESULTS: The results showed a significant increase of PBR binding sites value in platelet membranes from FM patients (B(max) was 5366+/-188 fmol/mg vs. controls, 4193+/-341 fmol/mg, mean+/-SEM) (**p<0.01) but not for affinity value (K(d) was 4.90+/-0.39 nM vs. controls, 4.74+/-0.39 nM, mean+/-SEM) (p>0.05). Symptom severity scores (pain and tiredness) were positively correlated with B(max). CONCLUSIONS: Our results showed an up-regulation of PBR in platelets of FM patients, and this seems to be related to the severity of fibromyalgic symptoms.