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Idiopathic pulmonary fibrosis (IPF) is a fatal disease with a median survival of 3–4 years after diagnosis. It is the most frequent form of a group of interstitial pneumonias of unknown etiology. Current available therapies prevent deterioration of lung function but no therapy has shown to improve survival. Periostin is a matricellular protein of the fasciclin 1 family. There is increased deposition of periostin in lung fibrotic tissues. Here we evaluated whether small interfering RNA or antisense oligonucleotide against periostin inhibits lung fibrosis by direct administration into the lung by intranasal route. Pulmonary fibrosis was induced with bleomycin and RNA therapeutics was administered during both acute and chronic phases of the disease. The levels of periostin and transforming growth factor-β1 in airway fluid and lung tissue, the deposition of collagen in lung tissue and the lung fibrosis score were significantly reduced in mice treated with siRNA and antisense against periostin compared to control mice. These findings suggest that direct administration of siRNA or antisense oligonucleotides against periostin into the lungs is a promising alternative therapeutic approach for the management of pulmonary fibrosis.

The protein C (PC) pathway has recently been suggested to play a role in the regulation of the inflammatory response. To further extend the anti-inflammatory effect of activated PC (APC) in vivo, particularly its biological relevance to human disease, the activity of APC in the mucosa of patients with Helicobacter pylori-associated gastritis and the effect of vacuolating cytotoxin (VacA), cytotoxin-associated antigen (CagA), and H. pylori lipopolysaccharide (LPS) on PC activation were evaluated. This study comprised 35 patients with chronic gastritis. There were 20 patients with and 15 without H. pylori infection. The levels of PC and APC-PC inhibitor (PCI) complex were measured by immunoassays. The level of PC was significantly decreased and the level of APC-PCI complex was significantly increased in biopsy specimens from gastric corpus and antrum in patients with H. pylori-associated gastritis as compared to H. pylori-negative subjects. The concentrations of VacA, CagA, and LPS were significantly correlated with those of the APC-PCI complex in biopsy mucosal specimens from the gastric corpus and antrum. H. pylori LPS, VacA, and CagA induced a dose-dependent activation of PC on the surface of monocytic cells. APC inhibited the secretion of tumor necrosis factor alpha (TNF-alpha) induced by H. pylori LPS. Overall, these results suggest that H. pylori infection is associated with increased APC generation in the gastric mucosa. The inhibitory activity of APC on TNF-alpha secretion may serve to protect H. pylori-induced gastric mucosal damage.

Enhanced activation of the clotting system has been recently implicated in the pathogenesis of vascular complications in patients with diabetes mellitus. Abnormalities of the anticoagulant system may constitute a potential trigger factor for the haemostatic activation observed in diabetic subjects. The current study aimed to evaluate anticoagulant activity in diabetic patients by assessing the plasma levels of activated protein C-protein C inhibitor complex; and by measuring the anticoagulant response to exogenous thrombomodulin. This study comprised 61 patients (34 men, 27 women) with non-insulin-dependent diabetes mellitus (NIDDM) of whom 22 showed microalbuminuria and 39 normoalbuminuria. Data obtained in 31 non-obese and non-diabetic subjects were available for comparison. The plasma levels of fibrinogen (p< 0.02), prothrombin fragment 1 + 2 (p< 0.05), fibrin monomer (p< 0.0001), protein C antigen (p< 0.005), total protein S antigen (p< 0.02), soluble thrombomodulin (p< 0.005) and soluble E-selectin (p< 0.005) were significantly higher in diabetic patients than in healthy subjects. The plasma level of activated protein C-protein C inhibitor complex (7.4 ± 3.8 vs 3.0 ± 0.4 pmol/l) was significantly higher (p< 0.0001) and the anticoagulant response to exogenous thrombomodulin (23.4 ± 2.6 vs 35.3 ± 3.0 ng/ml) was markedly lower (p= 0.005) in all diabetic patients than in healthy subjects. Cases with microalbuminuria presented low plasma levels of activated protein C-protein C inhibitor complex (5.5 ± 0.6 vs 8.6 ± 0.7 pmol/l, p< 0.05) and significantly decreased values of the anticoagulant response to exogenous thrombomodulin (16.5 ± 2.9 vs 23.4 ± 2.6 %, p= 0.03) as compared to those with normoalbuminuria. The present study suggests that the hyper-coagulable state in NIDDM is associated with an increased activation of protein C but with a poor plasma reactivity to the anticoagulant effect of thrombomodulin. [Diabetologia (1996) 39: 1455–1461]

Background: Previous in vitro studies suggested that Helicobacter pylori may inhibit the acid secretion of gastric parietal cells. The aim of this study was to investigate ultrastructurally the influence of H. pylori infection on the gastric parietal cell function in vivo. Methods: This study comprised 28 patients with chronic gastritis. Biopsy specimens were taken from the gastric body in all cases and examined by electron microscopy. Gastric parietal cells were counted in each ultrathin section and classified into secretory and non-secretory types. The pH of the gastric juice was also measured in all patients. Results: The number of parietal cells in the secretory phase was significantly lower in H. pylori W-infected (n = 16) patients than in those (n = 12) without H. pylori infection. The intragastric pH was significantly higher in patients with H. pylori-associated gastritis than in those without H. pylori infection. Parietal cells in secretory phase tended to decrease in proportion to the activity of the gastric mucosal inflammation. Conclusions: The results of this investigation suggest that H. pylori-associated gastritis is related to a decreased secretory activity of the gastric parietal cells.

Background: Recently, in vitro studies suggested that lactoferrin (Lf) might play an important role in the physiopathology of Helicobacter pylori-associated gastritis. However, whether Lf is present in the gastric juice and its relationship with H. pylori infection have not as yet been reported. In the present investigation the presence of Lf in gastric juice and its correlation with H. pylori infection were assessed. Methods: This study comprised 30 H. pylori-positive and 14 -negative patients with chronic gastritis. Gastric juice levels of Lf were measured with enzyme-linked immunoassays. Gastric juice concentration of Lf was also investigated in accordance with the histologic findings of biopsy specimens in the gastric body and antrum. Results: Lf concentration in gastric juice was significantly higher in H. pylori-positive than in -negative patients (P=0.033). The pH values are known to influence the levels of Lf. However, intragastric Lf levels were also significantly increased in H. pylori-positive patients as compared with H. pylori-negative patients after correcting the Lf levels for pH values (P = 0.029) or after adjusting the pH values of the gastric juice with NaHCO3 solution in both groups of patients (P = 0.0007). in addition, the gastric juice levels of Lf correlated significantly with the gastric mucosal concentrations of Lf in the gastric body (P < 0.005, r=0.568) and the antrum (P < 0.05, r=0.401). Conclusions: This study showed for the first time that Lf is present in gastric juice and that it correlates with H. pylori infection. Lf may constitute a good marker for H. pylori-associated gastritis. Although correlation does not prove causation, this study suggests that Lf might play an important role in the physiopathology of H. pylori-associated gastritis.