Peroxiredoxin 6 differentially regulates acute and chronic cigarette smoke–mediated lung inflammatory response and injury

Peroxiredoxin 6 (Prdx6) exerts its protective role through peroxidase activity against H?O? and phospholipid hydroperoxides. We hypothesized that targeted disruption of Prdx6 would lead to enhanced susceptibility to cigarette smoke (CS)-mediated lung inflammation and/or emphysema in mouse lung. Prdx6 null (Prdx6?/?mice exposed to acute CS showed no significant increase of inflammatory cell influx or any alterations in lung levels of proinflammatory cytokines compared to wild-type (WT) mice. Lung levels of antioxidant enzymes were significantly increased in acute CS-exposed Prdx6?/? compared to WT mice. Overexpressing (Prdx6?/?) mice exposed to acute CS showed significant decrease in lung antioxidant enzymes associated with increased inflammatory response compared to CS-exposed WT mice or air-exposed Prdx6?/? mice. However, chronic 6 months of CS exposure resulted in increased lung inflammatory response, mean linear intercept (Lm), and alteration in lung mechanical properties in Prdx6?/? when compared to WT mice exposed to CS. These data show that targeted disruption of Prdx6 does not lead to increased lung inflammatory response but is associated with increased antioxidants, suggesting a critical role of lung Prdx6 and several compensatory mechanisms during acute CS-induced adaptive response, whereas this protection is lost in chronic CS exposure leading to emphysema.     

Blood flow velocity in the arteries of the anterior cerebral artery complex in patients with an azygos anterior cerebral artery aneurysm: a transcranial color-coded sonography study

Objective

It is presumed that increased blood flow through the single azygos anterior cerebral artery (Az) may contribute to the formation of an Az aneurysm. The aim of this study was to assess the blood flow velocities in the arteries of the anterior cerebral artery (ACA) complex in patients with the Az aneurysm.

Patients and methods

A series of three patients (2 men, aged: 65, 52 and 41) with an aneurysm (unruptured in two cases) of the distal Az was examined. Blood flow velocities in the Az and the A1 segment of the ACA were measured by means of a transcranial color-coded duplex sonography (TCCS) and the Az to A1 segment (Az/A1) velocity ratio was calculated. The control group consisted of 22 healthy subjects (mean age: 44 years).

Results

There was a trend toward decreased (p = 0.06) mean blood flow velocity in the Az compared to the A2 segment of the ACA of the control group. Blood velocity in the A1 segment did not differ between the study and control groups. Pulsatility and resistance indices in the Az were similar to those in the A2 segment of the control group. There were no differences between the Az/A1 ratio in the study group and the A2/A1 velocity ratio in the control group.

Conclusion

Our results suggest that Az aneurysms are not associated with increased blood flow velocity in the Az. Possibly, a hemodynamic stress related to the Az bifurcation geometry, together with a bent course of this artery around the genu of the corpus callosum, predispose to aneurysm formation.     

Worldwide mortality from cirrhosis: an update to 2002

BACKGROUND/AIMS: Cirrhosis mortality has registered large changes over the last few decades. METHODS: Age-standardized (world standard) cirrhosis mortality rates per 100,000 were computed for 41 countries worldwide over the period 1980-2002 using data from the WHO mortality database. RESULTS: In the early 1980s, the highest rates were in Mexico, Chile (around 55/100,000 men and over 14/100,000 women), France, Italy, Portugal, Austria, Hungary and Romania (around 30-35/100,000 men and 10-15/100,000 women). Mortality from cirrhosis has been steadily declining in most countries worldwide since the mid or late 1970s (annual percent change, APC, between -5% and -1.5% in the last decade only for both sexes). In southern Europe, rates in the early 2000s were less than halved compared to earlier decades. In contrast, rates have been rising in Eastern European countries to reach extremely high values in the mid 1990s, and declined only thereafter. In the UK rates were still steadily rising (APC around +7% in men and +3% in women from England and Wales, and +9% in men and +7% in women from Scotland). CONCLUSIONS: Mortality from cirrhosis shows favourable trends in most countries of the world, following the reduction in alcohol consumption and hepatitis B and C virus infection. The steady upward trends observed over more recent calendar periods in the UK and central and eastern European countries are attributed to the persistent increase in the prevalence of alcohol consumption.     

Atrial septostomy in treatment of end-stage right heart failure in patients with pulmonary hypertension

BACKGROUND: Right ventricular (RV) failure is the main cause of death in patients with pulmonary hypertension (PH). Balloon atrial septostomy (BAS) is believed to relieve symptoms of PH by increasing systemic flow and reducing RV preload. METHODS: Fourteen BAS procedures were performed in 11 patients (5 men and 6 women; mean [+/- SD] age, 33 +/- 12 years) with RV failure in the course of PH that was refractory to conventional treatment. BAS consisted of a puncture of the interatrial septum and subsequent dilatations with balloons of increasing diameter in a step-by-step manner. RESULTS: After BAS, the mean oxygen saturation of aortic blood decreased (before, 93 +/- 4%; after, 84 +/- 4%; p = 0.001), while mean cardiac index increased (before, 1.54 +/- 0.34 L/min/m(2); after, 1.78 +/- 0.35 L/min/m(2); p = 0.001), resulting in a positive trend for mean systemic oxygen transport (before, 270 +/- 64 mL/min; after, 286 +/- 81 mL/min; p = 0.08). Pulmonary vascular resistance (PVR) slightly increased immediately after the procedure, and this rise inversely correlated with mixed venous blood partial oxygen pressure both before BAS (r = -0.69; p = 0.009) and after BAS (r = -0.64; p = 0.018). Mean functional class improved from 3.2 +/- 0.4 to 2.6 +/- 0.7 (p = 0.03) after 1 month. At follow-up (mean time to follow-up, 8.1 +/- 6.2 months; range, 0.8 to 20.2 months), seven patients died and two underwent lung transplantation. There was no difference in the survival rate compared to that obtained from National Institutes of Health equation. A significant size reduction in the created defect was observed in six patients, requiring repeat BAS procedures in three cases. CONCLUSIONS: The current BAS technique improves cardiac index and functional class without significant periprocedural complications, except for a transient increase in PVR related to acute desaturation of mixed venous blood. At long-term follow-up, a high incidence of spontaneous decrease in orifice size has been observed.     

Coronary venoplasty during the implantation of the cardiac resynchronisation device--a case report

We describe a case of a 76-year-old patient with advanced block in the His-Purkjnie system, who underwent implantation of a cardioverter-defibrillator with cardiac resynchronisation therapy. Complete heart block occurred during the insertion of the coronary sinus cathether. The implantation of the left ventricular (LV) lead was impossible due to difficult anatomy of the coronary venous system. The right ventricular pacing caused the further prolongation of the QRS duration and exacerbation of heart failure symptoms. Thus, the LV lead was successfully implanted during the second procedure after the balloon venoplasty of the lateral cardiac vein. The biventricular pacing was successful during 4 months follow-up.     

Beta-sheet core of human prion protein amyloid fibrils as determined by hydrogen/deuterium exchange

Propagation of transmissible spongiform encephalopathies is associated with the conversion of normal prion protein, PrP(C), into a misfolded, oligomeric form, PrP(Sc). Although the high-resolution structure of the PrP(C) is well characterized, the structural properties of PrP(Sc) remain elusive. Here we used MS analysis of H/D backbone amide exchange to examine the structure of amyloid fibrils formed by the recombinant human PrP corresponding to residues 90-231 (PrP90-231), a misfolded form recently reported to be infectious in transgenic mice overexpressing PrP(C). Analysis of H/D exchange data allowed us to map the systematically H-bonded beta-sheet core of PrP amyloid to the C-terminal region (staring at residue approximately 169) that in the native structure of PrP monomer corresponds to alpha-helix 2, a major part of alpha-helix 3, and the loop between these two helices. No extensive hydrogen bonding (as indicated by the lack of significant protection of amide hydrogens) was detected in the N-terminal part of PrP90-231 fibrils, arguing against the involvement of residues within this region in stable beta-structure. These data provide long-sought experimentally derived constraints for high-resolution structural models of PrP amyloid fibrils.