Prediction of acute pancreatitis risk based on PIP score in children with cystic fibrosis.

BACKGROUND: Currently no tools to predict risk of acute (AP) and recurrent pancreatitis (ARP) in children with cystic fibrosis (CF) are available. We assessed the prevalence of AP/ARP and tested the potential role of Pancreatic Insufficiency Prevalence (PIP) score in a cohort of children with CF. METHODS: We identified two groups of children, on the basis of presence/absence of AP/ARP, who were compared for age at diagnosis, clinical features, genotypes and sweat chloride level. PIP score was calculated for each patient. RESULTS: 10/167 (5.9%) experienced at least one episode of AP during follow up; 10/10 were pancreatic sufficient (PS). Patients with AP/ARP showed a PIP score ≤0.25 more frequently (6/10) than patients without AP/ARP. The odds ratio (95% CI) of developing pancreatitis was 4.54 (1.22-16.92) for patients with PIP <0.25 when compared with those who have a PIP score >0.25 (p 0.0151). PIP score was correlated with sweat chloride test (p < 0.01). CONCLUSION: PIP score, PS status and normal/borderline sweat chloride levels could be applied to predict pancreatitis development in children with CF. ARP could lead to pancreatic insufficiency.

The emerging role of large immunophilin FK506 binding protein 51 in cancer.

FK506 binding protein 51 (FKBP51) is an immunophilin physiologically expressed in lymphocytes. Very recently, aberrant expression of this protein was found in melanoma; FKBP51 expression correlates with melanoma aggressiveness and is maximal in metastatic lesions. FKBP51 promotes NF-κB activation and is involved in the resistance to genotoxic agents, including anthracyclines and ionizing radiation. FKBP51 is a cochaperone with peptidyl-prolyl isomerase activity that regulates several biological processes through protein-protein interaction. There is increasing evidence that FKBP51 hyperexpression is associated with cancer and this protein has a relevant role in sustaining cell growth, malignancy, and resistance to therapy. There is also evidence that FKBP ligands are potent anticancer agents, in addition to their immunosuppressant activity. In particular, rapamycin and its analogs have shown antitumor activity across a variety of human cancers in clinical trials. Although, classically, rapamycin actions are ascribed to inhibition of mTOR, recent studies indicate FKBP51 is also an important molecular determinant of the drug's anticancer activity. The aim of this article is to review the functions of FKBP51, especially in view of the recent findings that this protein is a potential oncogene when deregulated and a candidate target for signaling therapies against cancer.

Self-organization of polystyrenes into ordered microstructured films and their replication by soft lithography.

We report on the formation of ordered arrays of micrometric holes on the surface of polystyrene (PS) films cast from volatile solvents in the presence of humidity at different temperatures. The formation mechanism is investigated for PS having different molecular weights, polydispersities, and carboxylic terminations. Among the chosen materials, a highly regular honeycomb microstructured morphology is obtained on the surface of films prepared with dicarboxy-terminated PS with = 100,000. Experiments and observations on film formation indicate that polar groups are playing a fundamental role in this process. Tuning the surface tension by means of polar terminations allows the film morphology to be modified and in particular the preparation of two- or three-dimensional microstructured films. Finally, we show how these structures can be replicated by soft lithography and then used in the fields of photonic crystals and organic electronics.

Penbutolol and molsidomine synergism in angina pectoris. A double blind ergometric trial.

In order to test the additional efficacy of the combination of a beta blocker (penbutolol 40 mg single dose) with molsidomine (2 mg single dose), a double blind cross-over trial was performed in 30 patients with stable angina pectoris. Stress tests were done before and 1 h after the beta blocker alone and the combination therapy. Some training effect could be detected on comparing results from the first and second days. Combined therapy showed a better response of resting systolic arterial pressure, resting and maximal diastolic pressure, heart rate gain (from rest to maximal effort) and particularly in the angina severity score. All of these variables changed significantly in comparison to the beta blocker alone, 46 out of 60 post-drug ergometric studies were negative; of the 14 positive tests, 11 followed the beta blocker and only 3 the combined therapy. The combination of a preload reducer molsidomine and a beta blocker may be adequate for patients only partially compensated or with cardiomegaly and/or a depressed ejection fraction.