No abstract

Cinacalcet is effective in controlling the biochemical abnormalities in patients with primary hyperparathyroidism (PHPT) but it seems to be less effective on bone mineral density (BMD). In the same patients, bisphosphonates are reported to be effective on bone resorption but less effective on calcium and PTH excess. In this study, the efficacy of cinacalcet in combination with alendronate has been retrospectively evaluated in patients with PHPT. Twenty-three patients with PHPT who had not been operated were retrospectively investigated. Cinacalcet was evaluated in combination with alendronate in 10 of the 23 patients, and in monotherapy in 13 other patients. Serum calcium, phosphorus and PTH, 24 h urine calcium and phosphorus as well as BMD, evaluated by DXA and expressed as T-score, were measured before and after treatment. In all patients serum calcium and phosphorus and urinary calcium excretion were effectively and stably controlled and PTH was significantly decreased after treatment. There was no difference in the rate of serum calcium and PTH decrease between subjects treated with cinacalcet plus alendronate and those treated with cinacalcet alone. T-score increased by 9.6% at lumbar spine and 3.9% at femur level in the cinacalcet plus alendronate subgroup and was unchanged in the cinacalcet subgroup (P < 0.01). In patients with PHPT, the biochemical abnormalities are rapidly improved by cinacalcet regardless from the administration in monotherapy or in combination with alendronate. BMD is significantly improved in patients receiving cinacalcet plus alendronate and stable in those receiving cinacalcet in monotherapy.

We conclude that clusterin may have a protective effect against cigarette smoke-induced oxidative stress in lung fibroblasts.

Pemphigus Vulgaris is an autoimmune disease that results in blister formation in the epidermis and in mucosal tissues due to antibodies recognizing desmosomal cadherins, mainly desmoglein-3 and -1. Studies on the molecular mechanisms of Pemphigus have mainly been carried out using the spontaneously immortalized human keratinocyte cell line HaCaT or in primary keratinocytes. However, both cell systems have suboptimal features, with HaCaT cells exhibiting a large number of chromosomal aberrations and mutated p53 tumor suppressor, whereas primary keratinocytes are short-lived, heterogeneous and not susceptible to genetic modifications due to their restricted life-span. We have here tested the suitability of the commercially available human keratinocyte cell line hTert/KER-CT as a model system for research on epidermal cell adhesion and Pemphigus pathomechanisms. We here show that hTert cells exhibit a calcium dependent expression of desmosomal cadherins and are well suitable for typical assays used for studies on Pemphigus, such as sequential detergent extraction and Dispase-based dissociation assay. Treatment with Pemphigus auto-antibodies results in loss of monolayer integrity and altered localization of desmoglein-3, as well as loss of colocalization with flotillin-2. Our findings demonstrate that hTert cells are well suitable for studies on epidermal cell adhesion and Pemphigus pathomechanisms.

a b s t r a c tRationale: Clusterin expression may change in various human malignancies, including lung cancer. Patients with resectable non-small cell lung cancer (NSCLC), including adenocarcinoma, have a poor prognosis, with a relapse rate of 30-50% within 5 years. Nuclear factor kB (Nf-kB) is an intracellular protein involved in the initiation and progression of several human cancers, including the lung. Objectives: We investigate the role of clusterin and Nf-kB expression in predicting the prognosis of patients with early-stage surgically resected adenocarcinoma of the lung. Findings: The level of clusterin gradually decreased from well-differentiated to poorly differentiated adenocarcinomas. Clusterin expression was significantly higher in patients with low-grade adenocarcinoma, in early-stage disease and in women. Clusterin expression was inversely related to relapse and survival in both univariate and multivariate analyses. Finally, we observed an inverse correlation between Nf-kB and clusterin. Conclusions: Clusterin expression represents an independent prognostic factor in surgically resected lung adenocarcinoma and was proven to be a useful biomarker for fewer relapses and longer survival in patients in the early stage of disease. The inverse correlation between Nf-kB and clusterin expression confirm the previously reported role of clusterin as potent down regulator of Nf-kB.