Nutritional status and airflow obstruction: two independent contributors to CO diffusing capacity impairment in COPD

Background. The association between weight loss and Chronic Obstructive Pulmonary Disease (COPD) has been recognised from many years. Based on the evidence that nutritional status reflects metabolic disturbances in COPD, the relationship between body mass index (BMI), severity of airflow obstruction and CO diffusing capacity (DLCO), that is the functional hallmark of emphysema, is relevant to the management of COPD phenotypes. Methods. We reviewed 104 patients with COPD (82 males), aged 66±9 years (mean±SD). Height averaged 165±8 cm, weight 71±16 Kg, FEV1 50±18 (% of predicted), RV 169±49%, and DLCO 56±26%. Multiple linear regression was performed using BMI, FEV1 and RV, as explanatory variables for DLCO. Patients were also classified into four groups according to BMI ≤ 18.5 (low), > 18.5 and ≤ 25 (ideal), > 25 and ≤ 30 (overweight), > 30 (obese), and post-bronchodilator FEV1 < 50%. Using this categorisation, a two-factor analysis of variance, testing for interaction and main effects (BMI and FEV1) was performed as confirmatory analysis for the association between BMI (kg/m2), FEV1% and DLCO%. Results. FEV1 and BMI were significantly and independently associated to DLCO according to the equation: DLCO = -18.32 + 0.65·FEV1 + 1.59·BMI (R2 = 0.40, p<0.0001). The contribution of RV % to DLCO % was largely non-significant (p=0.16). A close relationship was found between BMI (kg/m2) and DLCO %, for all of the four BMI groups segregated by post-bronchodilator FEV1%, (p<.0001). No interaction was found between these two factors (p=0.30). Conclusion. Nutritional status as assessed by BMI contributes substantially to impairment of DLCO independently of the severity of airflow obstruction. This data confirms the association between emphysematous process and weight loss in advanced COPD, independent of the airflow obstruction severity

Leishmania Mitochondrial Peroxiredoxin Plays a Crucial Peroxidase-Unrelated Role during Infection: Insight into Its Novel Chaperone Activity

Two-cysteine peroxiredoxins are ubiquitous peroxidases that play various functions in cells. In Leishmania and related trypanosomatids, which lack catalase and selenium-glutathione peroxidases, the discovery of this family of enzymes provided the molecular basis for peroxide removal in these organisms. In this report the functional relevance of one of such enzymes, the mitochondrial 2-Cys peroxiredoxin (mTXNPx), was investigated along the Leishmania infantum life cycle. mTXNPx null mutants (mtxnpx−) produced by a gene replacement strategy, while indistinguishable from wild type promastigotes, were found unable to thrive in a murine model of infection. Unexpectedly, however, the avirulent phenotype of mtxnpx− was not due to lack of the peroxidase activity of mTXNPx as these behaved like controls when exposed to oxidants added exogenously or generated by macrophages during phagocytosis ex vivo. In line with this, mtxnpx− were also avirulent when inoculated into murine hosts unable to mount an effective oxidative phagocyte response (B6.p47phox−/− and B6.RAG2−/− IFN-γ−/− mice). Definitive conclusion that the peroxidase activity of mTXNPx is not required for parasite survival in mice was obtained by showing that a peroxidase-inactive version of this protein was competent in rescuing the non-infective phenotype of mtxnpx−. A novel function is thus proposed for mTXNPx, that of a molecular chaperone, which may explain the impaired infectivity of the null mutants. This premise is based on the observation that the enzyme is able to suppress the thermal aggregation of citrate synthase in vitro. Also, mtxnpx− were more sensitive than controls to a temperature shift from 25°C to 37°C, a phenotype reminiscent of organisms lacking specific chaperone genes. Collectively, the findings reported here change the paradigm which regards all trypanosomatid 2-Cys peroxiredoxins as peroxide-eliminating devices. Moreover, they demonstrate, for the first time, that these 2-Cys peroxiredoxins can be determinant for pathogenicity independently of their peroxidase activity

[Cardiological problems of heart transplantation. Results of the Italian experience]

L'articolo riporta dati relativi all'esperienza del Programma Nazionale di Trapianto Cardiaco. Viene inoltre effettuata un'analisi più nel dettaglio del centro di Pavia, che valuta sia l'outcome del pazienti che hanno subito un trapianto cardiaco, sia dal punto di vista clinico, sia dal punto di vista psicologico