The role of air pollution in myocardial remodeling.

BACKGROUND: Excessive air pollution in urban environments can impact morbidity and mortality. The authors evaluated the role of particulate matter2.5 (PM2.5) in structural, geometric, and functional remodeling in hearts, using an experimental model of myocardial infarction. METHODS AND FINDINGS: Seventy-five rats were divided into 5 groups: control (CG), CG exposed to PM2.5 pollution (CGP), myocardial infarcted group (MI), infarcted group immediately exposed to pollution (IGP-I), and infarcted group previously exposed to pollution and kept exposed after infarction (IGP-II). Greater deposition of interstitial collagen occurred in the left ventricle in CGP, MI, IGP-I, and IGP-II groups compared with that in controls (p = 0.002 CG vs CGP and p<0.0001 CG vs MI, IGP-I, and IGP-II). In the right ventricle, greater collagen deposition existed in CGP, MI, IGP-I, and IGP-II compared with that in CG (p<0.021 CG vs CGP and p<0.0001 CG vs MI, IGP-I, and IGP-II). At the end of the study, CG had a higher mean shortening fraction than the other groups had (p≤0.03). Left ventricular systolic diameter was lower in CG than in infarcted groups (p≤0.003). The infarcted groups had greater expression of TGF-ß (p≤0.04). PM2.5 increased the expression of TGF-ß in the IGP-II compared with the MI group (p = 0.004). The TNF-α gene was overexpressed in the IGP-II compared with the CGP group (p = 0.012). INF-γ gene expression was greater in IGP-II (p≤0.01). Oxidative stress analysis showed a higher glutathione concentration in CGP (p = 0.03), MI (p = 0.014), and IGP-I (p = 0.008) compared with that in CG. CONCLUSIONS: PM2.5 stimulates the deposition of fibrosis in the myocardium of healthy hearts, but not in infarcted hearts. PM2.5 modulates the inflammatory response, which was greater in the IGP-II group. It also modulates oxidative stress in healthy hearts but not in infarcted hearts.

Biological characterization of a myotoxin phosphoplipase A2 homologue purified from the venom of the snake Bothrops moojeni

A myotoxin phospholipase A2 homologue, BmooMtx, was isolated from the venom of Bothrops moojeni by a combination of ion-exchange chromatography on DEAE-Sephacel column and gel filtration on Sephadex G-75. SDS-PAGE showed the enzyme to be a monomer with a molecular weight of 16,500. BmooMtx induced release of creatine kinase and morphological analyses indicated that it provoked an intense myonecrosis, with visible leukocyte infiltrate and damaged muscle cells 24 hours after injection. Anti-BmooMTx antibodies partially neutralized the myotoxic activity of BmooMtx and crude B. moojeni venom, as judged by determination of plasma creatine kinase levels and histological evaluation of skeletal muscle in mice. Anti-BmooMTx antibodies were effective in reducing the plasma creatine kinase levels of crude B. alternatus and B. leucurus venoms, evidencing immunological cross-reactivity between BmooMTx and other bothropic venoms. Intraplantar (i.pl.) injection of BmooMtx (1 to 15 ìg/animal) caused a dose- and time-dependent hyperalgesia and edematogenic responses. Dexamethasone (0.4 mg/kg), meloxicam (2 mg/kg) and promethazine (5 mg/kg) markedly reduced the hyperalgesia. Our data suggest that these drugs may likely serve as complementary therapies in cases of accidents with Bothrops moojeni, provided that such pharmacological treatments are administered immediately after the incident.

Purification and biochemical characterization of Eumiliin from Euphorbia milii var. hislopii latex.

A protease, which we designate Eumiliin, was isolated from the latex of Euphorbia milii var. hislopii by a combination of ion-exchange chromatographic steps using DEAE-Sephacel and gel-filtration with Sephadex G-75. Eumiliin is a monomeric protein with an apparent molecular mass of 30 kDa by SDS-PAGE under reducing conditions and gave one main peak at 29,814 KDa in MALDI-TOF/TOF mass spectrometry. Eumiliin has caseinolytic and fibrinogenolytic activities, but no hemorrhagic or defibrinating activities. The enzyme readily hydrolyzes the Aalpha-chain of fibrinogen and, more slowly, the Bbeta-chain. Its fibrinogenolytic activity is inhibited by beta-mercaptoethanol and leupeptin. In contrast, EDTA and benzamidine did not affect the activity of Eumiliin. The caseinolytic activity of Eumiliin had a pH optimum of 8.0 and was stable in solution at up to 40 degrees C; activity was completely lost at >or=80 degrees C. Intraplantar injection of Eumiliin (1-25 microg/paw) caused a dose- and time-dependent hyperalgesia, which peaked 1-5h after enzyme injection. Intraplantar injection of Eumiliin (1-25 microg/paw) also caused an oedematogenic response that was maximal after 1h. Morphological analyses indicated that Eumiliin induced an intense myonecrosis, with visible leukocyte infiltrate and damaged muscle cells 24h after injection.