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Objectives Vascular endothelial growth factor (VEGF) is thought to play an important role in systemic sclerosis (SSc) pathogenesis. It was found to be upregulated in the serum and in the affected skin of scleroderma patients. However, its involvement in scleroderma lung disease is not clear. This study aimed to evaluate VEGF concentration in the bronchoalveolar lavage fluid (BALF) of scleroderma patients with interstitial lung disease, to correlate the cytokine levels in plasma and in the lung with pulmonary functional, radiological and cellular parameters, and with the progression of lung disease. Methods BALF and plasma VEGF concentrations were analysed by ELISA in 55 SSc patients with lung disease and 17 controls. Cytokine real-time PCR messenger RNA expression in alveolar macrophages was assessed. Lung involvement progression was evaluated after a 1-year follow-up. Results VEGF was found to be significantly lower in the BALF of scleroderma patients compared with controls. The lowest concentrations were observed in SSc patients with alveolitis. A decreased VEGF expression in alveolar macrophages was found in SSc patients with alveolitis. VEGF concentration in BALF correlated inversely with the ground glass score on high-resolution CT and with BALF neutrophil cell count. Moreover, SSc patients with a lower VEGF concentration showed a worsening in the interstitial score at follow-up. Conclusions Scleroderma interstitial lung disease is characterised by a VEGF deficiency. Lower concentrations were found in patients with progression of lung disease.

Patency of the ductus arteriosus (PDA) and bronchopulmonary dysplasia (BPD) development represent severe affections for premature newborns, therefore the research of early markers for these two conditions is really important. The aim of this study is to analyze epithelial lining fluid (ELF) Neutrophil-gelatinase-associated lipocalin (NGAL) levels for prediction of lung injury or possible involvement of this molecule in PDA. Only scarce and contrasting results have previously been published in this field. In contrast, this molecule, included in a large macromolecular complex together with matrix metalloproteinase-9 (MMP-9), is considered an acceptable marker of infectious/inflammatory processes, cancer monitoring and induction of apoptotic pathway. NGAL was detected in 28 pre-term newborns by means of a commercially available kit in bronchoalveolar lavage fluid (BALF). The results have been corrected to ELF levels, by the urea method, to eliminate bias due to BALF collection. ELF NGAL levels were found significantly increased both in infants developing BPD or in those affected by PDA. By means of multivariate logistic regression analysis the significances were confirmed after adjusting for possible interfering variables such as gestational age and concomitant presence of both PDA and BPD. Our results stress the involvement of NGAL in the mechanisms leading to BPD and also suggest a possible association with PDA, which is often linked to prematurity and BPD development, probably due to the involvement of inflammatory and angiogenetic processes in both pathologies.

Background. Pregnancy-associated plasma protein A (PAPP-A) is a zinc-binding matrix metalloproteinase (MMP) that was shown to increase in acute coronary syndromes. Calcium channel blockers (CCB) can influence the production of several MMPs, but no study, so far, has assessed the association between use of CCB and PAPP-A levels. The aim of the present cross-sectional study was to evaluated if, among older hypertensive adults, PAPP-A levels differ according to use of CCB. Methods. Data are from the baseline evaluation of the ilSIRENTE study, which enrolled 364 participants 80 years old or older. For the present study, we selected 314 participants with hypertension. Analyses of covariance were performed to evaluate the differences in PAPP-A levels according to use of CCB. Results. Mean age of participants was 85.6 years (standard deviation [SD] 4.8), 206 (66%) were women; 58 participants (19%) were using a CCB. After adjusting for potential confounders, concentration of PAPP-A was significantly lower in CCB users than in nonusers (1.58 mIU/L, 95% confidence interval [CI], 1.37‐1.81 vs 1.86 mIU/L, 95% CI, 1.74‐1.98; p ¼ .03). This association was still consistent after exclusion of participants with cardiovascular disease (1.53 mIU/L, 95% CI, 1.30‐1.80 vs 1.90 mIU/L, 95% CI, 1.78‐2.03; p ¼ .01). Conclusions. Use of CCB is associated with lower levels of PAPP-A. These findings need to be confirmed in prospective studies.

Preterm newborns developing retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) show persistently low levels of insulin-like growth factor-I (IGF-I) in sera. They also present higher free IGF-I concentrations in epithelial lining fluids (ELFs) and lung tissues. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase that dissociates three binding proteins from the active form of IGF-I, namely free IGF-I. The present study analyzes the ELF concentrations of free IGF-I, PAPP-A, and their ratios in preterm newborns developing or not BPD, defined as O2 dependence at 36 wk postmenstrual age. Bronchoalveolar lavage fluids of 41 infants (34 without and 7 with BPD) were analyzed on the 2nd and 4th day after birth. Infants developing BPD showed increased ELF free IGF-I and decreased PAPP-A concentrations on both days 2 and 4 compared with newborns without BPD. A nonsignificant trend between these 2 days was observed for free IGF-I (increasing) and PAPP-A (decreasing). On the same days, the free IGF-I-to-PAPP-A ratio was always significantly higher in patients developing BPD. These differences were more significant than those of IGF-I or PAPP-A when individually evaluated. A multivariate analysis confirmed the significance for free IGF-I on day 4, whereas the ratio was confirmed on both days 2 and 4. The same ratio was significantly correlated with some indexes of disease severity, such as hours of oxygen administration, days of hospitalization, and ROP severity scores. Finally, the ratio between ELF free IGF-I and PAPP-A appears to be a useful marker for lung injury of premature newborns.

Background Even though the gene encoding for IGF-I is considered of most importance amongst blood pressure-regulating genes in mouse models, little and discordant data are available in literature for what concerns a possible relationship between blood pressure and serum free IGF-I values in humans. In addition, no information is available on type 1 diabetes patients. Aim: Our aim is to analyze the relationship between systolic and diastolic blood pressure and serum free IGF-I and IGFBP-3 levels in subjects suffering from type 1 diabetes. Results: A highly significant inverse correlation was observed between serum free IGF-I levels and both systolic and diastolic blood pressure in subjects affected with type 1 diabetes. Similar but less significant relationships were observed for IGFBP-3, whose levels were also significantly and directly correlated with those of free IGF-I. The correlation between systolic and diastolic blood pressures with free IGF-I and between systolic blood pressure and IGFBP-3 levels were confirmed after adjusting for age, gender, age at diagnosis, disease duration, familial history, HBA1c, and amount of insulin administered by multivariate logistic regression analysis. A decrease in free IGF-I and IGFBP-3 levels, along with increases in blood pressure, significantly influenced the presence of diabetic complications, confirming how these molecules may be considered as severity markers for patients with type 1 diabetes as well as risk factors for altered pressure control linked diseases.