CD40-dependent activation of phosphatidylinositol 3-kinase/AKT pathway inhibits apoptosis of human cultured mesangial cells induced by oxidized LDL.

Deposition of atherogenic lipoproteins is associated with various glomerular diseases. In particular, oxidized LDL (oxLDL) may affect mesangial cells and favour the development of glomerulosclerosis. The aim of the present study was to investigate on cultured human mesangial cells (HMC) whether oxLDL induces apoptosis by a mechanism dependent on the inhibition of Akt survival pathway, and whether the engagement of mesangial CD40 by its ligand CD154 inhibits the apoptotic effect of oxLDL. Tunel assays demonstrated that incubation of HMC for 24 h with oxLDL, but not with unmodified LDL, induced a dose-dependent increase in apoptosis of HMC associated with a decrease in Akt phosphorylation. Enzymatic kinase assay showed that also the Akt activity was reduced in a dose-dependent manner by treatment with oxLDL. Stimulation of mesangial CD40 with sCD154 rescued HMC from oxLDL-dependent apoptosis, while two unrelated pharmacological inhibitors of PI3K LY294002 and wortmannin abrogated this anti-apoptotic effect, suggesting an involvement of the PI3K/Akt pathway. Moreover CD40 stimulation maintained an elevated phosphorylation of Akt and preserved its enzymatic activity in the presence of oxLDL. Indeed, CD154 induced a rapid enhancement in Akt enzymatic activity, that was temporarily correlated with the association of CD40 with TRAF3, TRAF6, c-Cbl and the p85 subunit of PI3K. In conclusion, these results suggest that CD40 stimulation protects HMC from toxic effects of oxLDL by promoting PI3K/Akt-dependent cell survival.

[Management of overweight and obese patient. New acquisition]. / Management del paziente in sovrappeso e obeso. Recenti acquisizioni.

Obesity is a chronic disease and prevalence and incidence are progressively increasing. Treatment of obesity is important to reduce mortality and associated diseases, like diabetes mellitus, hypertension, abnormal blood lipid levels, coronary heart disease, thromboembolic disease, cancer (endometrial, gallbladder, cervical, ovarian, breast, prostate and colorectal), polycystic ovary syndrome (PCOS), gallbladder disease, respiratory disease, arthritis, gout. Most of these pathologies profits by a modest weight loss (5-10%). A correct management of obesity should include integration of therapeutic strategies, that we have actually at disposal: diet, physical training, behaviour therapy, pharmacologic therapy and surgery. We should get together low-calorie and low-fat diet with behaviour change and physical training. Physical training induces a significant weight loss and reduces cardiovascular risks and insulin resistance. Orlistat, that reduces up to 30% lipid adsorption, is a valid remedy if with an adequate diet. A new drug, sibutramine, shows efficacy: it increases satiety and energy expenditure caused by thermogenesis in brown adipose tissue. Surgical approaches including some procedures, are indicated for great obesity (BMI >40).

[Management of obese patients: surgical therapy]. / Management del paziente obeso. Terapia chirurgica.

At present, the management of obesity includes integration of therapeutic strategies such as diet, physical training, behaviour therapy and pharmacologic therapy. An increased number of selected patients with morbid obesity, where medical therapy was ineffective, have been surgically treated in the last years due to less invasive surgical techniques, such as laparoscopic surgery. Main operations include gastroplasty, adjustable gastric banding, gastric bypass, bilio-pancreatic diversion. A less invasive procedure is intragastric balloon, i.e. a temporary device which is removed after few months. Surgery shows efficacy to induce weight loss and duration in time. All obese patients can't be treated by the same operation. Available surgical techniques are different and have to be chosen in each case according to the patient's clinical conditions.

Atrial fibrillation and mitral prolapse in a subject affected by Refetoff syndrome.

Inappropriate secretion of TSH (IST) refers to a heterogeneous group of syndromes in which patients show unsuppressed TSH levels in spite of high serum free thyroid hormone concentrations. It has been recognised that IST can be due to both thyroid hormone resistance (RTH) and pituitary TSH-secreting tumours. The former can be generalised (GRTH) or pituitary (PRTH) if the resistance is more severe in the pituitary than in the remaining tissues. This case report describes a peculiar coexistence of atrial fibrillation and mitral valve prolapse in a patient affected by generalized resistance to thyroid hormone. This finding is suggestive for a major and almost physiological sensitivity of the myocardium to the thyroid hormones activity which in the course of years may determine the modifications responsible for the pathologies described.