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RATIONALE: In emphysema, chronic inflammation, including protease-antiprotease imbalance, is responsible for declining pulmonary function and progressive cachexia. OBJECTIVES: To evaluate variations of inflammatory mediators and alpha(1)-antitrypsin levels after lung volume reduction surgery (LVRS) compared with respiratory rehabilitation. METHODS: A total of 28 patients with moderate to severe emphysema, who underwent video-assisted thoracoscopic LVRS, were compared with 26 similar patients, who refused operation and followed a standardized rehabilitation program, and to a matched healthy group. Respiratory function, body composition, circulating inflammatory mediators, and alpha(1)-antitrypsin levels were evaluated before and 12 months after treatment. Gene expression levels of inflammatory mediators and protease-antiprotease were assessed in emphysematous specimens from 17 operated patients by matching to normal tissue from resection margins. MEASUREMENTS AND MAIN RESULTS: Significant improvements were only obtained after surgery in respiratory function (FEV(1), +25.2%, P < 0.0001; residual volume [RV], -19.5%, P < 0.0001; diffusing lung capacity for carbon monoxide, +3.3%, P < 0.05) and body composition (fat-free mass, +6.5%, P < 0.01; fat mass, +11.9%, P < 0.01), with decrement of circulating inflammatory mediators (TNF-alpha, -22.2%, P < 0.001; IL-6, -24.5%, P < 0.001; IL-8, -20.0%, P < 0.001) and increment of antiprotease levels (alpha(1)-antitrypsin, +27.0%, P < 0.001). Supportive gene expression analysis demonstrated active inflammation and protease hyperactivity in the resected emphysematous tissue. Reduction of TNF-alpha and IL-6 and increment of alpha(1)-antitrypsin levels significantly correlated with reduction of RV (P = 0.03, P = 0.009, and P = 0.001, respectively), and partially with increment of fat-free mass (P = 0.03, P = 0.02, and P = 0.09, respectively). CONCLUSIONS: LVRS significantly reduced circulating inflammatory mediators and increased antiprotease levels over respiratory rehabilitation, also improving respiratory function and nutritional status. Correlations of inflammatory mediators and antiprotease levels with RV and, partly, with body composition suggest that elimination of inflammatory emphysematous tissue may explain clinical improvements after surgery. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, the microencapsulation of the MgAl-hydrotalcite (HTlc) and diclofenac (DIK) intercalation product (HTlc-DIK) was realized in order to obtain a composite system for colonic drug delivery. Eudragit® S or Eudragit® L were used as polymers for preparation of microparticles (MPs). MPs were prepared by using a properly modified oil-in-oil solvent evaporation method. A 1:5 or 1:10 w/w HTlc-DIK/polymer ratios were employed. An experimental design was applied in order to assess the preparation variable effects on the qualitative MP appearance. Improved MP preparations were achieved when 7–13ml of acetone-ethanol solution was employed at both HTlc-DIK/polymer ratios. The MPs were tested for in vitro drug release. DIK release from Eudragit® L MPs at pH 6.8 reached 26–35% within 25–30min at both HTlc-DIK/polymer ratios and no further increase was observed when the pH was shifted to 7.5. DIK release from Eudragit® S MPs at pH 7.5 reached for both ratios 70% after 6–8h. The obtained results showed that hydrotalcite intercalation compound can be microencapsulated without missing the intercalated compound and the resulted composite MPs showed good characteristics. Besides HTlc-DIK/Eudragit® S MPs possess improved features with respect to HTlc-DIK/Eudragit® L MPs. For this reason, HTlc-DIK/Eudragit® S MPs could be promising for drug delivery either to the distal part of small intestine or to the colon. [Copyright &y& Elsevier]

Groeger A M, Esposito V, De Luca A, Cassandro R, Tonini G, Ambrogi V, Baldi F, Goldfarb R, Mineo T C, Baldi A & Wolner E (2004) Histopathology 44, 54–63 Prognostic value of immunohistochemical expression of p53, bax, Bcl-2 and Bcl-xL in resected non-small-cell lung cancers : Some experimental evidence suggests that in lung cancer, development, progression and an increased proliferation rate can be linked to apoptosis-related factors. In this study we evaluated the possible role of p53 and Bcl-2 gene family members as prognostic factors for non-small-cell lung cancer. : We investigated the immunohistochemical expression of p53 and Bcl-2 gene family members (bax, Bcl-2 and Bcl-xL) in 94 non-small-cell lung cancer specimens to establish the role of these genes in lung cancer pathogenesis, and to evaluate their prognostic importance. The expression of Bcl-2 was correlated with a shorter patient survival time and with the nodal status of the neoplasm. We also found frequent over-expression of bax and Bcl-xL to be of no prognostic significance. Finally, we found no correlation between frequent detection of aberrant p53 protein and expression of either Bcl-2, bax or Bcl-xL or with patient survival time. : This study confirms a relevant role for apoptosis-regulatory proteins in the pathogenesis of lung cancer, and highlights the possible role of Bcl-2 as a prognostic factor for this tumour. [ABSTRACT FROM AUTHOR]